@article{tucker_archibald_cohen_sommer_keene_minter_delk_2021, title={What Is Your Diagnosis?}, volume={35}, ISSN={["1938-2871"]}, DOI={10.1647/21-00060}, abstractNote={A captive 38-year-old female Chilean flamingo (Phoenicopterus chilensis) presented with an approximately 4-day history of being listless and moving slowly behind the flock. The flamingo had been housed at the North Carolina Zoo (Asheboro, NC, USA) for the previous 28 years. This bird’s medical history included mild intermittent lameness associated with pododermatitis and a cloacal papilloma diagnosed via biopsy 9 years earlier. The flamingo habitat at the North Carolina Zoo covers approximately 12.23 15.2 m with a 3.2 3 5.6-m indoor holding area. The mixed sex (9:8 ratio) flock of 17 flamingoes are fed a diet consisting of Mazuri Flamingo Complete pellets (Mazuri Exotic Animal Nutrition, St Louis, MO, USA). On presentation, the flamingo weighed 1.85 kg (historical weight 2–2.4 kg), with a body condition score (BCS) of 1.5/5. Tachycardia was auscultated and later confirmed by electrocardiogram (ECG) to be a ventricular tachycardia of approximately 400 beats per minute (Fig 1). Complete blood count revealed a monocytosis (31%; reference range, 0.0%–7.8%) with a total white blood cell count of 22 610 cells/lL (reference range, 2900– 20 000 cells/lL). An echocardiogram (SonoSite M-Turbo, Bothell, WA, USA) performed with a C11X (8–5-MHz transducer) semilinear probe revealed severe dilation of the left ventricle and decreased cardiac systolic function (fractional shortening 18.3% compared with 81.5% in an ageand sex-matched clinically normal flamingo) (Fig 2A through D). Comparison ECG and echocardiographic findings were obtained on a sex-matched 32-year-old female Chilean flamingo from the same flock. This apparently healthy younger bird had a heart rate of 200 beats per minute with sinus rhythm, more robust systolic left ventricular function, and no cardiac chamber dilation. Further diagnostic imaging and medical management of the cardiac abnormalities were discussed.}, number={4}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Tucker, Samuel and Archibald, Kate and Cohen, Eli B. and Sommer, Samantha and Keene, Bruce W. and Minter, Larry J. and Delk, Katie W.}, year={2021}, month={Dec}, pages={486–493} } @article{meurs_williams_deprospero_friedenberg_malarkey_ezzell_keene_adin_defrancesco_tou_2021, title={A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat}, volume={16}, ISSN={["1750-1172"]}, DOI={10.1186/s13023-021-01740-5}, abstractNote={Abstract Background Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation. Results A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001). Conclusion This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy. }, number={1}, journal={ORPHANET JOURNAL OF RARE DISEASES}, author={Meurs, Kathryn M. and Williams, Brian G. and DeProspero, Dylan and Friedenberg, Steven G. and Malarkey, David E. and Ezzell, J. Ashley and Keene, Bruce W. and Adin, Darcy B. and DeFrancesco, Teresa C. and Tou, Sandra}, year={2021}, month={Feb} } @article{k. o'donnell_adin_atkins_defrancesco_keene_tou_meurs_2021, title={Absence of known feline MYH7 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy}, volume={52}, ISSN={["1365-2052"]}, DOI={10.1111/age.13074}, abstractNote={SummaryHypertrophic cardiomyopathy (HCM) is the most common cause of heart disease in the domestic cat with a genetic predisposition in a few breeds. In the Maine Coon and Ragdoll breeds, two variants associated with the HCM phenotype have been identified in the cardiac myosin binding protein C gene (MYBPC3; p.Ala31Pro and p.Arg820Trp respectively), and a single variant has been identified in the myosin heavy chain gene (MYH7; p.Glu1883Lys) in one domestic cat with HCM. It is not known if these variants influence the development of HCM in other cohorts of the feline population. The objective of this study was to evaluate the presence of the known MYBPC3 and MYH7 variants in a population of cats with HCM. DNA was isolated from samples collected from non‐Ragdoll and non‐Maine Coon domestic cats diagnosed with HCM through the North Carolina State University College of Veterinary Medicine and genotyped for the three variants. One‐hundred and three DNA samples from cats with HCM were evaluated from domestic shorthair, domestic longhair and purebred cats. All samples were wt for the MYBPC3 and MYH7 variants. Although this study was limited by its inclusion of cats from one tertiary hospital, the lack of these MYBPC3 and MYH7 variants in this feline HCM population indicates that the clinical utility of genetic testing for these variants may be isolated to the two cat breeds in which these variants have been identified. Further studies to identify the causative variants for the feline HCM population are warranted.}, number={4}, journal={ANIMAL GENETICS}, author={K. O'Donnell and Adin, D. and Atkins, C. E. and DeFrancesco, T. and Keene, B. W. and Tou, S. and Meurs, K. M.}, year={2021}, month={Aug}, pages={542–544} } @article{walker_defrancesco_bonagura_keene_meurs_tou_kurtz_aona_barron_mcmanamey_et al._2022, title={Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure*}, volume={40}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2021.02.001}, abstractNote={Dilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy.Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF).A retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan-Meier curves and the Cox proportional-hazards model.The median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs.Prior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Walker, A. L. and DeFrancesco, T. C. and Bonagura, J. D. and Keene, B. W. and Meurs, K. M. and Tou, S. P. and Kurtz, K. and Aona, B. and Barron, L. and McManamey, A. and et al.}, year={2022}, month={Apr}, pages={99–109} } @misc{atkins_keene_defrancesco_tou_chetboul_cote_ettinger_fox_hamlin_mochel_et al._2021, title={Letter to the editor regarding "Efficacy of adding ramipril (VAsotop) to the combination of furosemide (Lasix) and pimobendan (VEtmedin) in dogs with mitral valve degeneration: The VALVE trial"}, volume={35}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16035}, abstractNote={Dear Editors, The manuscript entitled Efficacy of adding ramipril (VAsotop) to the combination of furosemide (Lasix) and pimobendan (VEtmedin) in dogs with mitral valve degeneration: The VALVE trial reports a study which sought to answer the question “could pimobendan be all that is needed beyond loop diuretics to manage congestive heart failure (CHF) in myxomatous mitral valve disease (MMVD)?” This was done by prospectively comparing the efficacy of pimobendan + ramipril + furosemide (triple treatment) to pimobendan + furosemide (double treatment) to treat new-onset CHF caused by MMVD. While agreeing with the authors that this question has merit, we share several comments and questions regarding applicability of their study results to current practice. During the VALVE trial, worsening signs of CHF were primarily managed with progressively larger diuretic dosages, as opposed to other potential pharmacological interventions such as greater renin-angiotensin-aldosterone system (RAAS) suppression, alternative diuretic use, higher pimobendan dosing, and arterial vasodilator treatment. While the angiotensinconverting enzyme inhibitor (ACEI) ramipril (VASOTOP) was begun at a once daily dosage according to label recommendation, the initial furosemide dosage (median, 8 mg/kg/d), high by current clinical standards, was increased to as much as 15 mg/kg/d, before predefined treatment failure was reached; ramipril dosage was increased (doubled) in only 3 dogs. Spironolactone dosing was left to the clinicians' discretion (added to baseline treatment in only 13 dogs, 8 in the triple treatment group, and 5 dogs in the double treatment group). The VALVE trial did not assess the efficacy of RAAS suppression using biomarkers. Therefore, the question of whether ramipril adequately or optimally suppressed RAAS, while failing to improve survival in the face of these diuretic dosages, remains unanswered. We are also concerned that dogs in both treatment groups received ACEI for an average of 9 months before entering the study (44% of triple treatment group vs 26% of double treatment group; P = .02), indicating that over one-quarter of the double treatment group (the no ACEI group) previously had received an ACEI—and for a duration longer than the median 7.6 months that these dogs remained in the study. This is important because it is known that RAAS suppression before the onset of CHF has favorable effects on cardiac remodeling. Although unknowable by the authors at the time of the VALVE trial design, other studies completed during the 10-year duration of the VALVE trial have demonstrated significant benefit from greater, longer, and more broad-spectrum RAAS suppression (eg, higher or q12h ACEI dosing and mineralocorticoid antagonist [MRA] inclusion) in treating proteinuria and CHF. Because the VALVE trial was performed under Good Clinical Practice guidelines, owner adherence to the trial protocol was quantified. It would be useful to know whether those measurements identified “adherence parity” between the 2 treatment groups, thus eliminating 1 potential source of unintentional bias. Ramipril, a narrow-spectrum RAAS suppressant (ie, it causes no direct MRA effect), was tested as an “add-on” to drugs providing symptomatic relief (pimobendan and furosemide). Although the absence of an MRA as part of the test article is understandable because of the timing of the VALVE study design, its absence impairs our understanding of the potential role that true RAAS suppression (ie, more RAAS suppression than ACE inhibition alone) might play in managing CHF caused by MMVD. It is now known that incomplete RAAS suppression (aldosterone breakthrough) is common with either ACEI or angiotensin II receptor blockers (ARB) in normal dogs challenged with furosemide or amlodipine; with ACEI in natural MMVD before CHF (without furosemide); and in MMVD with CHF in dogs receiving ACEI and furosemide. Furthermore, inclusion of MRAs in therapeutic protocols has improved survival in CHF caused by MMVD. Although it has not been directly investigated, it is likely that the high doses of furosemide used in the VALVE Trial, with greater RAAS stimulatory potential, enhanced the propensity for aldosterone breakthrough. In dogs treated with ACEI and ARBs, there is an estimated 30% to 40% incidence of aldosterone breakthrough at conventional furosemide dosages, and a proportional clinical benefit is seen with broad-spectrum RAAS suppression. For this Received: 11 January 2021 Accepted: 12 January 2021}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Atkins, Clarke and Keene, Bruce and DeFrancesco, Teresa C. and Tou, Sandra and Chetboul, Valerie and Cote, Etienne and Ettinger, Stephen and Fox, Philip R. and Hamlin, Robert L. and Mochel, Jonathan P. and et al.}, year={2021}, month={Mar}, pages={698–699} } @article{deprospero_kerry a. o'donnell_defrancesco_keene_tou_adin_atkins_meurs_2021, title={Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016)}, volume={259}, ISSN={["1943-569X"]}, DOI={10.2460/javma.20.05.0291}, abstractNote={Abstract OBJECTIVE To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers. ANIMALS 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD. PROCEDURES Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests. RESULTS Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds. }, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={DeProspero, Dylan J. and Kerry A. O'Donnell and DeFrancesco, Teresa C. and Keene, Bruce W. and Tou, Sandra P. and Adin, Darcy B. and Atkins, Clarke E. and Meurs, Kathryn M.}, year={2021}, month={Dec}, pages={1428–1432} } @article{williams_friedenberg_keene_tou_defrancesco_meurs_2021, title={Use of whole genome analysis to identify shared genomic variants across breeds in canine mitral valve disease}, volume={6}, ISSN={["1432-1203"]}, DOI={10.1007/s00439-021-02297-w}, abstractNote={Familial mitral valve prolapse in human beings has been associated with several genetic variants; however, in most cases, a known variant has not been identified. Dogs also have a naturally occurring form of familial mitral valve disease (MMVD) with similarities to the human disease. A shared genetic background and clinical phenotype of this disease in some dog breeds has indicated that the disease may share a common genetic cause. We evaluated DNA from 50 affected dogs from five different dog breeds in a whole genome sequencing approach to identify shared variants across and within breeds that could be associated with MMVD. No single causative genetic mutation was found from the 50 dogs with MMVD. Ten variants were identified in 37/50 dogs around and within the MED13L gene. These variants were no longer associated with MMVD when evaluated with a larger cohort including both affected and unaffected dogs. No high/moderate impact variants were identified in 10/10 miniature poodles, one was identified in 10/10 Yorkshire Terriers and 10/10 dachshunds, respectively, 14 were identified in 10/10 Miniature schnauzers, and 19 in 10/10 CKCS. Only one of these could be associated with the cardiac valve (Chr12:36801705, COL12A1; CKCS) but when evaluated in an additional 100 affected CKCS the variant was only identified in 84/100 affected dogs, perhaps indicating genetic heterogeneity in this disease. Our findings indicate that development of MMVD in the dog may be related to a combination of genetic and environmental factors that impact specific molecular pathways rather than a single shared genetic variant across or within breeds.}, journal={HUMAN GENETICS}, author={Williams, Brian and Friedenberg, Steven G. and Keene, Bruce W. and Tou, Sandy P. and DeFrancesco, Teresa C. and Meurs, Kathryn M.}, year={2021}, month={Jun} } @article{coleman_defrancesco_griffiths_lascelles_kleisch_atkins_keene_2020, title={Atenolol in cats with subclinical hypertrophic cardiomyopathy: a double-blind, placebo-controlled, randomized clinical trial of effect on quality of life, activity, and cardiac biomarkers}, volume={30}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2020.06.002}, DOI={10.1016/j.jvc.2020.06.002}, abstractNote={To compare quality of life (QOL) and activity measures between healthy control cats and cats with subclinical hypertrophic cardiomyopathy (HCM), and to evaluate the effect of oral atenolol therapy on QOL, activity, and circulating biomarkers in cats with subclinical HCM. Thirty-two client-owned cats with subclinical HCM and 27 healthy control cats. Owner responses to a QOL questionnaire, circulating cardiac biomarker concentrations, and accelerometer-based activity measures were compared prospectively in cats with and without HCM, and in cats with HCM before and after treatment with oral atenolol (6.25 mg/cat q 12 h) for 6 months. Owner-assessed activity of daily living score was lower in cats with HCM than in cats in controls (p=0.0420). No differences were identified between control cats and cats with HCM for any activity variable. Compared with placebo, treatment with atenolol was associated with a lower baseline-adjusted mean ± SD heart rate (157 ± 30 vs. 195 ± 20 bpm; p=0.0001) and rate-pressure product (22,446 ± 6,237 vs. 26,615 ± 4,623 mmHg/min; p=0.0146). A treatment effect of atenolol on QOL or activity was not demonstrated. This study failed to identify an effect of subclinical HCM on owner-assessed QOL or activity or a treatment effect of atenolol on these variables at the dosage evaluated. These findings do not support a treatment benefit of atenolol for the goal of symptom reduction in cats with subclinical HCM.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Coleman, A. E. and DeFrancesco, T. C. and Griffiths, E. H. and Lascelles, B. D. X. and Kleisch, D. J. and Atkins, C. E. and Keene, B. W.}, year={2020}, month={Aug}, pages={77–91} } @article{lakhdhir_viall_alloway_keene_baumgartner_ward_2020, title={Clinical presentation, cardiovascular findings, etiology, and outcome of myocarditis in dogs: 64 cases with presumptive antemortem diagnosis (26 confirmed postmortem) and 137 cases with postmortem diagnosis only (2004-2017)}, volume={30}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2020.05.003}, abstractNote={This study describes presentation, cardiovascular abnormalities, etiology, and outcome of canine myocarditis in geographic areas not endemic for Trypanosoma or Leishmania.Sixty-four (presumed antemortem diagnosis) and 137 (postmortem diagnosis only) client-owned dogs at two tertiary care facilities were included.Medical records of dogs with clinical or histopathological diagnosis of myocarditis were reviewed retrospectively.Common examination findings in dogs with a presumed antemortem diagnosis included fever (21%) and heart murmur (19%). Median cardiac troponin I was 12.2 ng/mL (range: 0.2-808.0 ng/mL), and troponin exceeded 1.0 ng/mL in 26 of 29 (90%) dogs. Ventricular ectopy was the most common arrhythmia (54%), whereas decreased left ventricular systolic function was the most common echocardiographic abnormality (56%). An infectious etiology was diagnosed in 35 of 64 (55%) dogs. Confirmed infectious etiologies included bacterial sepsis (n = 9) or extension of endocarditis (3), toxoplasmosis or neosporosis (3), parvovirus (2), and one case each of bartonellosis, trypanosomiasis, leptospirosis, and dirofilariasis. Median survival time was 4 days (range: 0-828 days) for all dogs vs. 82 days for dogs who survived at least 2 weeks after diagnosis. Presence of pericardial effusion or azotemia was a significant predictor of non-survival. The most common inflammatory infiltrate on histopathology was neutrophilic (47%), and 20 of 137 (14.5%) dogs had concurrent bacterial endocarditis on postmortem.Bacterial infection was the most common confirmed etiology of myocarditis in this study. Prognosis for canine myocarditis is guarded and similar to that reported for infective endocarditis. Criteria for the antemortem diagnosis of canine myocarditis are suggested.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Lakhdhir, S. and Viall, A. and Alloway, E. and Keene, B. and Baumgartner, K. and Ward, J.}, year={2020}, month={Aug}, pages={44–56} } @article{adin_atkins_domenig_defrancesco_keene_tou_stern_meurs_2020, title={Renin-angiotensin aldosterone profile before and after angiotensin-converting enzyme-inhibitor administration in dogs with angiotensin-converting enzyme gene polymorphism}, volume={34}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15746}, DOI={10.1111/jvim.15746}, abstractNote={AbstractBackgroundAn angiotensin‐converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied.HypothesisWe hypothesized that dogs with the polymorphism would show alternative renin‐angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE‐inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE‐inhibitor administration.AnimalsTwenty‐one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism.MethodsThis retrospective study utilized stored samples from 8 ACE gene polymorphism‐negative (PN) dogs and 13 ACE gene polymorphism‐positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups.ResultsThe classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85‐184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00‐33.92) after enalapril.Conclusions and Clinical ImportanceThe ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE‐inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Adin, Darcy and Atkins, Clarke and Domenig, Oliver and DeFrancesco, Teresa and Keene, Bruce and Tou, Sandra and Stern, Joshua A. and Meurs, Kathryn M.}, year={2020}, month={Mar}, pages={600–606} } @article{ward_kussin_tropf_tou_defrancesco_keene_2020, title={Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy}, volume={34}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15920}, DOI={10.1111/jvim.15920}, abstractNote={AbstractBackgroundPimobendan is frequently used off‐label for treatments of cats with congestive heart failure (CHF). Concern exists regarding the safety of pimobendan in cats with outflow tract obstruction (OTO).ObjectivesIn cats treated with pimobendan, incidence of adverse effects will not differ between cats with OTO vs cats with nonobstructive cardiomyopathy.AnimalsTwo‐hundred sixty cats with CHF (57 with OTO, 203 with nonobstructive disease).MethodsRetrospective medical record review. Groups were compared using 2‐sample t‐tests, Wilcoxon rank‐sum tests, and Fisher exact tests.ResultsCompared to cats with nonobstructive cardiomyopathy, cats with OTO were younger (8.9 [interquartile range (IQR) 6.6] vs 10.8 [6.3] years, P = .0036), more likely to have a heart murmur (51/57 [90%] vs 76/203 [37.8%] cats, P < .0001), more likely to manifest CHF as pulmonary edema (53/57 [83%] vs 144/203 [70.9%] cats, P = .0004), and less likely to have pleural effusion (19/57 [33%] vs 122/203 [60.1%] cats, P = .0005). Adverse effects suspected to be related to pimobendan administration occurred in 12/260 cats (4.6%), including 11/203 cats (5.4%) with nonobstructive cardiomyopathy and 1/57 cat (2%) with OTO (P = .7). Pimobendan was discontinued due to adverse effects in 4/260 cats (1.5%), 3 with nonobstructive disease and 1 with OTO (P = 1.0). Acute adverse hemodynamic effects after pimobendan administration were not detected in any cats.Conclusions and Clinical ImportancePimobendan is well tolerated in cats with cardiomyopathy and CHF, regardless of the presence of OTO.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Ward, Jessica L. and Kussin, Efrem Z. and Tropf, Melissa A. and Tou, Sandra P. and DeFrancesco, Teresa C. and Keene, Bruce W.}, year={2020}, month={Nov}, pages={2211–2222} } @article{hamlin_keene_2020, title={Species differences in cardiovascular physiology that affect pharmacology and toxicology}, volume={23-24}, ISSN={["2468-2020"]}, DOI={10.1016/j.cotox.2020.07.004}, abstractNote={The accuracy with which preclinical studies performed on infrahuman mammals predict the efficacy and safety of potential new therapeutics intended for human use is a topic of interest and concern to preclinical scientists, physicians, veterinarians, regulators, and patients everywhere. Factors that impact the potential accuracy of preclinical assessments of safety and efficacy in surrogate species for humans include substantial differences in the mechanisms of cardiac repolarization and excitation–contraction coupling, as well as in the isoforms of the heart's contractile proteins. Some species are so similar to humans that they suffer the same spontaneous heart diseases — and yet so different that toxic doses of drugs or interventions that would be instantly fatal to a human have literally no effect on them. These differences are in part explained by the sometimes enormous differences in size and scale among species and in part by genetic and biochemical differences that we have only recently begun to understand. In reviewing some of the more striking species differences and similarities in cardiovascular physiology, this article hopes to stimulate interest in and inform the choices of scientists involved in surrogate model selection as they work to improve both the positive and negative predictive value of preclinical drug studies.}, journal={CURRENT OPINION IN TOXICOLOGY}, author={Hamlin, Robert L. and Keene, Bruce W.}, year={2020}, pages={106–113} } @article{boswood_gordon_haggstrom_vanselow_wess_stepien_oyama_keene_bonagura_macdonald_et al._2020, title={Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study}, volume={34}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15753}, abstractNote={AbstractBackgroundThe Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF).ObjectivesTo describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF.AnimalsOne hundred and thirty‐five, and 73 dogs that did or did not develop CHF, respectively.Materials and methodsThe following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home‐measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points.ResultsThe most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF.Conclusions and Clinical ImportanceDogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Boswood, Adrian and Gordon, Sonya G. and Haggstrom, Jens and Vanselow, Martin and Wess, Gerhard and Stepien, Rebecca L. and Oyama, Mark A. and Keene, Bruce W. and Bonagura, John and MacDonald, Kristin A. and et al.}, year={2020}, month={May}, pages={1108–1118} } @article{meurs_friedenberg_kolb_saripalli_tonino_woodruff_olby_keene_adin_yost_et al._2019, title={A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death}, volume={138}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-019-01973-2}, DOI={10.1007/s00439-019-01973-2}, abstractNote={The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.}, number={5}, journal={Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Friedenberg, Steven G. and Kolb, Justin and Saripalli, Chandra and Tonino, Paola and Woodruff, Kathleen and Olby, Natasha J. and Keene, Bruce W. and Adin, Darcy B. and Yost, Oriana L. and et al.}, year={2019}, month={Feb}, pages={515–524} } @article{keene_atkins_bonagura_fox_haggstrom_fuentes_oyama_rush_stepien_uechi_et al._2019, title={ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs}, volume={33}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85064530654&partnerID=MN8TOARS}, DOI={10.1111/jvim.15488}, abstractNote={AbstractThis report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Keene, Bruce W. and Atkins, Clarke E. and Bonagura, John D. and Fox, Philip R. and Haggstrom, Jens and Fuentes, Virginia Luis and Oyama, Mark A. and Rush, John E. and Stepien, Rebecca and Uechi, Masami and et al.}, year={2019}, month={May}, pages={1127–1140} } @article{adin_moga_keene_fogle_hopkinson_weyhrauch_marks_ruderman_rosoff_2019, title={Clinical ethics consultation in a tertiary care veterinary teaching hospital}, volume={254}, ISSN={["1943-569X"]}, DOI={10.2460/javma.254.1.52}, number={1}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Adin, Christopher A. and Moga, Jeannine L. and Keene, Bruce W. and Fogle, Callie A. and Hopkinson, Heather R. and Weyhrauch, Charity A. and Marks, Steven L. and Ruderman, Rachel J. and Rosoff, Philip M.}, year={2019}, month={Jan}, pages={52–60} } @article{vollmar_vollmar_keene_fox_reese_kohn_2019, title={Irish wolfhounds with subclinical atrial fibrillation: progression of disease and causes of death}, volume={24}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2019.05.004}, abstractNote={To evaluate the frequency of dilated cardiomyopathy (DCM) and cardiac death (CD) in Irish wolfhounds (IW) with subclinical atrial fibrillation (AF) and to compare cardiac and all-cause mortality to those of a contemporaneous control group of apparently healthy IW with sinus rhythm.Fifty-two IW with AF, but without echocardiographic evidence of DCM or other cardiac disease, and an age- and gender-matched control cohort of 52 apparently healthy IW.Data from 1552 IW were retrospectively evaluated. Fifty-two dogs with subclinical AF were compared with 52 IW controls. Time from initial diagnosis to development of DCM was recorded, and survival data were analyzed using cumulative incidence functions.26/52 AF dogs developed DCM. At study end, in the AF and control group each, 49/52 AF dogs had died, three remained alive. Death in the AF cohort was attributed to CD in 22/49 dogs (12 congestive heart failure [CHF], 10 sudden cardiac deaths [SCD]), while 27 dogs died from non-CD. In the control group, significantly fewer dogs developed DCM (11/52 dogs, p=0.004), even fewer died from CD (5/49; three CHF, two SCD; p=0.001). The odd ratios (95% confidence interval) for dogs with AF vs. controls to develop DCM was 3.7 (1.6-8.8) and to die from CD was 7.2 (2.4-21.2). Median all-cause survival for AF IWs (CD, 36.3 months; non-CD, 33.2 months) did not differ significantly from the control group (CD, 28.6 months, p=0.377; non-CD, 45.3 months, p=0.631).IW with subclinical AF commonly develop DCM and die from cardiac death.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Vollmar, C. and Vollmar, A. and Keene, B. and Fox, P. R. and Reese, S. and Kohn, B.}, year={2019}, month={Aug}, pages={48–57} } @article{fox_keene_lamb_schober_chetboul_fuentes_payne_wess_hogan_abbott_et al._2019, title={Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy}, volume={33}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15609}, abstractNote={AbstractBackgroundEpidemiologic knowledge regarding noncardiovascular and all‐cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence‐based healthcare guidelines.ObjectivesTo characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all‐cause mortality in AH and pHCM cats.AnimalsA total of 1730 client‐owned cats (722 AH, 1008 pHCM) from 21 countries.MethodsRetrospective, multicenter, longitudinal, cohort study. Long‐term health data were extracted by medical record review and owner/referring veterinarian interviews.ResultsNoncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight‐loss‐vomiting‐diarrhea‐anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All‐cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all‐cause survival was significantly shorter in pHCM (P = .0001).Conclusions and Clinical ImportanceAll‐cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fox, Philip R. and Keene, Bruce W. and Lamb, Kenneth and Schober, Karsten E. and Chetboul, Valerie and Fuentes, Virginia Luis and Payne, Jessie Rose and Wess, Gerhard and Hogan, Daniel F. and Abbott, Jonathan A. and et al.}, year={2019}, month={Nov}, pages={2572–2586} } @article{vollmar_vollmar_keene_fox_reese_kohn_2019, title={Dilated cardiomyopathy in 151 Irish Wolfhounds: Characteristic clinical findings, life expectancy and causes of death}, volume={245}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2018.12.018}, abstractNote={Dilated cardiomyopathy (DCM) is an important cause of morbidity in Irish Wolfhounds (IW), a breed also predisposed to neoplastic and orthopedic diseases that shorten life expectancy. The objective of this study was to investigate survival and causes of death in IW with DCM and to characterise the clinical findings of DCM over time. Data from cardiovascular examinations performed in 1591 IW, including echocardiography and electrocardiography, were retrospectively evaluated. IW with DCM on medical therapy with long term longitudinal follow-up were included in this study (n=151; 95 males, 56 females). Based on their clinical status at initial diagnosis, IW were classified into one of three groups: preclinical DCM with sinus rhythm (PC-DCM-SR, n=35), preclinical DCM with atrial fibrillation (PC-DCM-AF, n=87), and congestive heart failure with DCM and AF (CHF-DCM-AF, n=29). Survival data were analyzed using cumulative incidence functions, Kaplan-Meier and Cox regression. CHF was predominantly characterized by chylous pleural and mild pericardial effusions. Causes of death were cardiac (CD) in 73/151 and non-cardiac (non-CD) in 62/151; 16 dogs remained alive at study end. The majority of deaths in both preclinical DCM groups were non-CD (PC-DCM-AF=51.9% non-CD, 48.1% CD; PC-DCM-SR, 65.5% non-CD, 34.5% CD). In the CHF-DCM-AF group most dogs (89.6%) experienced a CD. Median survival of the CHF-DCM-AF group (7.3 months) was significantly shorter than in the PC-DCM-AF group (21.9 months) or PC-DCM-SR group (29.1 months, P=0.001). CHF-DCM-AF in IW was associated with reduced life expectancy and CD, while most IW with preclinical DCM died from non-cardiac causes.}, journal={VETERINARY JOURNAL}, author={Vollmar, C. and Vollmar, A. and Keene, B. W. and Fox, P. R. and Reese, S. and Kohn, B.}, year={2019}, month={Mar}, pages={15–21} } @article{adin_defrancesco_keene_tou_meurs_atkins_aona_kurtz_barron_saker_et al._2019, title={Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type}, volume={21}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2018.11.002}, abstractNote={Canine dilated cardiomyopathy (DCM) can result from numerous etiologies including genetic mutations, infections, toxins, and nutritional imbalances. This study sought to characterize differences in echocardiographic findings between dogs with DCM fed grain-free (GF) diets and grain-based (GB) diets.Forty-eight dogs with DCM and known diet history.This was a retrospective analysis of dogs with DCM from January 1, 2015 to May 1, 2018 with a known diet history. Dogs were grouped by diet (GF and GB), and the GF group was further divided into dogs eating the most common grain-free diet (GF-1) and other grain-free diets (GF-o). Demographics, diet history, echocardiographic parameters, taurine concentrations, and vertebral heart scale were compared between GB, all GF, GF-1, and GF-o groups at diagnosis and recheck.Dogs eating GF-1 weighed less than GB and GF-o dogs, but age and sex were not different between groups. Left ventricular size in diastole and systole was greater, and sphericity index was less for GF-1 compared with GB dogs. Diastolic left ventricular size was greater for all GF compared with that of GB dogs. Fractional shortening, left atrial size, and vertebral heart scale were not different between groups. Taurine deficiency was not identified in GF dogs, and presence of congestive heart failure was not different between groups. Seven dogs that were reevaluated after diet change (6 received taurine supplementation) had clinical and echocardiographic improvement.Dietary-associated DCM occurs with some GF diets and can improve with nutritional management, including diet change. The role of taurine supplementation, even without deficiency, is uncertain.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Adin, Darcy and DeFrancesco, Teresa and Keene, Bruce and Tou, Sandra and Meurs, Kathryn and Atkins, Clarke and Aona, Brent and Kurtz, Kari and Barron, Lara and Saker, Korinn and et al.}, year={2019}, month={Feb}, pages={1–9} } @article{bartoszuk_keene_toaldo_pereira_summerfield_matos_glans_2019, title={Holter monitoring demonstrates that ventricular arrhythmias are common in cats with decompensated and compensated hypertrophic cardiomyopathy}, volume={243}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2018.11.005}, abstractNote={Arrhythmias can complicate cardiac disease in cats and are a potential cause of sudden death. The aim of this study was to evaluate the presence and nature of cardiac arrhythmias, and the potential correlation between plasma serum troponin I (cTnI) concentrations and the presence or severity of arrhythmias in cats with decompensated (dHCM) and compensated hypertrophic cardiomyopathy (cHCM). Forty one client-owned cats were studied: 16 with cHCM, 15 with dHCM and 10 healthy control cats. Physical examination, echocardiography, cTnI and 24-h Holter recordings were obtained in all cats and thoracic radiographs in cats with dHCM. Cats in both HCM groups were followed for 1 year after their initial Holter examination. The median (range) number of ventricular premature complexes (VPCs) over 24h was 867 (1-35,160) in cats with dHCM, 431 (0-18,919) in cats with cHCM and 2 (0-13) in healthy control cats. The median number of episodes of ventricular tachycardia (VTach) was 0 (0-1497) in dHCM and 0.5 (0-91) in cats with cHCM. The number of VPCs, VTach episodes and heart rate was not different between the HCM groups. Plasma serum troponin I was highest in the cats with dHCM, but there was no correlation between cTnI concentration and the number of arrhythmias. Thirteen of 31 cats with HCM died, but an association with the presence and complexity of ventricular arrhythmias was not observed. Compared to healthy cats, ventricular arrhythmias were common in cats with cHCM and dHCM, but neither presence nor complexity of arrhythmias could be linked to prognosis.}, journal={VETERINARY JOURNAL}, author={Bartoszuk, U. and Keene, B. W. and Toaldo, M. Baron and Pereira, N. and Summerfield, N. and Matos, J. Novo and Glans, T. M.}, year={2019}, month={Jan}, pages={21–25} } @article{fox_keene_lamb_schober_chetboul_fuentes_wess_payne_hogan_motsinger-reif_et al._2018, title={International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study}, volume={32}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Fox, P. R. and Keene, B. W. and Lamb, K. and Schober, K. A. and Chetboul, V. and Fuentes, V. L. and Wess, G. and Payne, J. R. and Hogan, D. F. and Motsinger-Reif, A. and et al.}, year={2018}, pages={930–943} } @article{boswood_gordon_haggstrom_wess_stepien_oyama_keene_bonagura_macdonald_patteson_et al._2018, title={Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with preclinical myxomatous mitral valve disease receiving pimobendan or placebo: The EPIC study}, volume={32}, number={1}, journal={Journal of Veterinary Internal Medicine}, author={Boswood, A. and Gordon, S. G. and Haggstrom, J. and Wess, G. and Stepien, R. L. and Oyama, M. A. and Keene, B. W. and Bonagura, J. and MacDonald, K. A. and Patteson, M. and et al.}, year={2018}, pages={72–85} } @article{meurs_adin_k. o'donnell_keene_atkins_defrancesco_tou_2019, title={Myxomatous mitral valve disease in the miniature poodle: A retrospective study}, volume={244}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2018.12.019}, abstractNote={Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disease in the dog. The natural history of the disease is wide ranging and includes patients without clinical signs as well as those with significant clinical consequences from cardiac arrhythmias, pulmonary hypertension and/or congestive heart failure. The factors that determine which dogs remain asymptomatic and which develop clinical disease are not known. Disease characteristics could be breed or family related; some breeds of dogs, particularly the Cavalier King Charles spaniels, develop MMVD at an early age. The purpose of this study was to retrospectively characterize MMVD in the miniature poodle, a commonly affected breed in which MMVD has not been well characterized. Thirty-two miniature poodles met the inclusion criteria. Mean age was 11 ± three years. Clinical signs included exercise intolerance, syncope and coughing. Eighteen dogs were classified as ACVIM Stage B1, 12 as stage B2, and two as stage C. Mean vertebral heart scale (VHS) was 10.2 (±standard deviation of 0.9); 15 of 28 dogs had a VHS <10.3. One dog had radiographic evidence of congestive heart failure. Mean diastolic left ventricle dimension normalized to body weight was 1.6 (±0.4) and mean systolic was 0.8 (±0.3). Mitral valve prolapse was subjectively classified as mild or moderate in 19 dogs and severe in two. In the miniature poodles reported here, MMVD appears to be a fairly late onset disease and often is a mild phenotype.}, journal={VETERINARY JOURNAL}, author={Meurs, K. M. and Adin, D. and K. O'Donnell and Keene, B. W. and Atkins, C. E. and DeFrancesco, T. and Tou, S.}, year={2019}, month={Feb}, pages={94–97} } @article{rosoff_moga_keene_adin_fogle_ruderman_hopkinso_weyhrauch_2018, title={Resolving Ethical Dilemmas in a Tertiary Care Veterinary Specialty Hospital: Adaptation of the Human Clinical Consultation Committee Model}, volume={18}, ISSN={["1536-0075"]}, DOI={10.1080/15265161.2017.1409824}, abstractNote={Technological advances in veterinary medicine have produced considerable progress in the diagnosis and treatment of numerous diseases in animals. At the same time, veterinarians, veterinary technicians, and owners of animals face increasingly complex situations that raise questions about goals of care and correct or reasonable courses of action. These dilemmas are frequently controversial and can generate conflicts between clients and health care providers. In many ways they resemble the ethical challenges confronted by human medicine and that spawned the creation of clinical ethics committees as a mechanism to analyze, discuss, and resolve disagreements. The staff of the North Carolina State University Veterinary Hospital, a specialty academic teaching institution, wanted to investigate whether similar success could be achieved in the tertiary care veterinary setting. We discuss the background and rationale for this method, as well as the approach that was taken to create a clinical ethics committee.}, number={2}, journal={AMERICAN JOURNAL OF BIOETHICS}, author={Rosoff, Philip M. and Moga, Jeannine and Keene, Bruce and Adin, Christopher and Fogle, Callie and Ruderman, Rachel and Hopkinso, Heather and Weyhrauch, Charity}, year={2018}, pages={41–53} } @misc{rosoff_ruderman_moga_keene_adin_fogle_hopkinson_weyhrauch_2018, title={Response to Open Peer Commentaries on "Resolving Ethical Dilemmas in a Tertiary Care Veterinary Specialty Hospital: Adaptation of the Human Clinical Consultation Committee Model"}, volume={18}, ISSN={["1536-0075"]}, DOI={10.1080/15265161.2017.1413439}, abstractNote={We are gratified that our article, “Resolving Ethical Dilemmas in a Tertiary Care Veterinary Specialty Hospital: Adaptation of the Human Clinical Consultation Committee Model” (Rosoff et al. 2018),...}, number={2}, journal={AMERICAN JOURNAL OF BIOETHICS}, author={Rosoff, Philip M. and Ruderman, Rachel and Moga, Jeannine and Keene, Bruce and Adin, Christopher and Fogle, Callie and Hopkinson, Heather and Weyhrauch, Charity}, year={2018}, pages={W7–W10} } @article{ward_mclaughlin_burzette_keene_2019, title={The effect of a surgical safety checklist on complication rates associated with permanent transvenous pacemaker implantation in dogs}, volume={22}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2018.11.001}, abstractNote={To determine whether use of a surgical safety checklist (SSC) would reduce the rate of major complications after permanent transvenous pacemaker implantation in dogs . The study included one hundred ninety-nine dogs undergoing pacemaker implantation for bradyarrhythmias at an academic teaching hospital. A service-specific SSC was developed and implemented for cardiac catheterization procedures in 2015. Medical records were reviewed to extract relevant clinical and procedural data for cases with (SSC [+]) and without (SSC [−]) a checklist. Owners or referring veterinarians were contacted for outcome and survival data. Major complications occurred in 25/199 (12.6%) dogs. Incidence of major complications was significantly lower in SSC [+] dogs compared with SSC [−] dogs (1/45 procedures vs 24/144 procedures; p = 0.019). Dogs with SSCs were more likely to receive antibiotics within 5 min of the first incision ( p = 0.0082) and to receive antibiotics every 90 min throughout the procedure as prescribed ( p = 0.001) compared with dogs without SSCs. Incidence of cardiac death was lower in SSC [+] dogs compared with SSC [−] dogs ( p = 0.0012), but checklist use was not associated with increased survival time (all-cause or cardiac). On average, 91% of checklist components were completed for each SSC; minor changes in record-keeping protocols could increase compliance. Use of an SSC was associated with a decrease in the major complication rate and an increase in compliance with antibiotic protocols during pacemaker implantation. Results of this study support the use of an SSC in veterinary cardiology procedures.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Ward, J. and McLaughlin, A. and Burzette, R. and Keene, B.}, year={2019}, month={Apr}, pages={72–83} } @article{ward_lisciandro_keene_tou_defrancesco_2017, title={Accuracy of point-of-care lung ultrasonography for the diagnosis of cardiogenic pulmonary edema in dogs and cats with acute dyspnea}, volume={250}, ISSN={["1943-569X"]}, DOI={10.2460/javma.250.6.666}, abstractNote={Abstract OBJECTIVE To determine the accuracy of a point-of-care lung ultrasonography (LUS) protocol designed to diagnose cardiogenic pulmonary edema (CPE) in dyspneic dogs and cats. DESIGN Diagnostic test evaluation. ANIMALS 76 dogs and 24 cats evaluated for dyspnea. PROCEDURES Dogs and cats were evaluated by LUS; B lines were counted at 4 anatomic sites on each hemithorax. A site was scored as positive when > 3 B lines were identified. Animals with ≥ 2 positive sites identified on each hemithorax were considered positive for CPE. Medical records were evaluated to obtain a final diagnosis (reference standard) for calculation of the sensitivity and specificity of LUS and thoracic radiography for the diagnosis of CPE. RESULTS Dogs and cats with a final diagnosis of CPE had a higher number of positive LUS sites than did those with noncardiac causes of dyspnea. Overall sensitivity and specificity of LUS for the diagnosis of CPE were 84% and 74%, respectively, and these values were similar to those of thoracic radiography (85% and 87%, respectively). Use of LUS generally led to the misdiagnosis of CPE (ie, a false-positive result) in animals with diffuse interstitial or alveolar disease. Interobserver agreement on LUS results was high (κ > 0.85). CONCLUSIONS AND CLINICAL RELEVANCE LUS was useful for predicting CPE as the cause of dyspnea in dogs and cats, although this technique could not be used to differentiate CPE from other causes of diffuse interstitial or alveolar disease. Point-of-care LUS has promise as a diagnostic tool for dyspneic dogs and cats.}, number={6}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Ward, Jessica L. and Lisciandro, Gregory R. and Keene, Bruce W. and Tou, Sandra P. and DeFrancesco, Teresa C.}, year={2017}, month={Mar}, pages={666–675} } @article{meurs_stern_atkins_adin_aona_condit_defrancesco_reina-doreste_keene_tou_et al._2017, title={Angiotensin-converting enzyme activity and inhibition in dogs with cardiac disease and an angiotensin-converting enzyme polymorphism}, volume={18}, ISSN={["1752-8976"]}, url={https://europepmc.org/articles/PMC5843865}, DOI={10.1177/1470320317737184}, abstractNote={Objective: The objective of this study was to evaluate angiotensin-converting enzyme (ACE) activity in dogs and with and without an ACE polymorphism in the canine ACE gene, before and after treatment with an ACE inhibitor. Methods: Thirty-one dogs (20 wild-type, 11 ACE polymorphism) with heart disease were evaluated with ACE activity measurement and systolic blood pressure before and after administration of an ACE inhibitor (enalapril). Results: Median pre-treatment ACE activity was significantly lower for ACE polymorphism dogs than for dogs with the wild-type sequence (P=0.007). After two weeks of an ACE inhibitor, ACE activity was significantly reduced for both genotypes (wild-type, P<0.0001; ACE polymorphism P=0.03); mean post-therapy ACE activity was no different between the groups. Conclusion: An ACE polymorphism is associated with lower levels of ACE activity. Dogs with the polymorphism still experience suppression of ACE activity in response to an ACE inhibitor. It is possible that the genetic status and ACE activity of dogs may impact the response of dogs with this variant to an ACE inhibitor.}, number={4}, journal={JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM}, author={Meurs, Kathryn M. and Stern, Joshua A. and Atkins, Clarke E. and Adin, Darcy and Aona, Brent and Condit, Julia and DeFrancesco, Teresa and Reina-Doreste, Yamir and Keene, Bruce W. and Tou, Sandy and et al.}, year={2017}, month={Oct} } @article{boswood_haggstrom_gordon_wess_stepiens_oyama_keene_bonagura_macdonald_patteson_et al._2017, title={Effect of pimobendan in Dogs with preclinical myxomatous mitral valve disease and cardiomegaly: The EPIC study - A randomized clinical trial}, volume={62}, number={2}, journal={Kleintier-Praxis}, author={Boswood, A. and Haggstrom, J. and Gordon, S. G. and Wess, G. and Stepiens, R. L. and Oyama, M. A. and Keene, B. W. and Bonagura, J. and MacDonald, K. A. and Patteson, M. and et al.}, year={2017}, pages={64–87} } @article{meurs_friedenberg_williams_keene_atkins_adin_aona_defrancesco_tou_mackay_et al._2018, title={Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration}, volume={232}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2017.12.002}, abstractNote={Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here.}, journal={VETERINARY JOURNAL}, author={Meurs, Kathryn and Friedenberg, S. G. and Williams, B. and Keene, B. W. and Atkins, C. E. and Adin, D. and Aona, B. and DeFrancesco, Teresa and Tou, S. and Mackay, T. and et al.}, year={2018}, month={Feb}, pages={16–19} } @article{nolan_arkans_lavine_defrancesco_myers_griffith_posner_keene_tou_gieger_et al._2017, title={Pilot study to determine the feasibility of radiation therapy for dogs with right atrial masses and hemorrhagic pericardial effusion}, volume={19}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2016.12.001}, DOI={10.1016/j.jvc.2016.12.001}, abstractNote={To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs. Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial. A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined. No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days. In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Nolan, M.W. and Arkans, M.M. and LaVine, D. and DeFrancesco, Teresa and Myers, J.A. and Griffith, E.H. and Posner, L.P. and Keene, B.W. and Tou, S.P. and Gieger, Tracy and et al.}, year={2017}, month={Apr}, pages={132–143} } @article{carter_motsinger-reif_krug_keene_2017, title={The Effect of Heart Disease on Anesthetic Complications During Routine Dental Procedures in Dogs}, volume={53}, ISSN={["1547-3317"]}, DOI={10.5326/jaaha-ms-6512}, abstractNote={ABSTRACTDental procedures are a common reason for general anesthesia, and there is widespread concern among veterinarians that heart disease increases the occurrence of anesthetic complications. Anxiety about anesthetizing dogs with heart disease is a common cause of referral to specialty centers. To begin to address the potential effect of heart disease on anesthetic complications in dogs undergoing anesthesia for routine dental procedures, we compared anesthetic complications in 100 dogs with heart disease severe enough to trigger referral to a specialty center (cases) to those found in 100 dogs without cardiac disease (controls) that underwent similar procedures at the same teaching hospital. Medical records were reviewed to evaluate the occurrence of anesthetic complications. No dogs died in either group, and no significant differences were found between the groups in any of the anesthetic complications evaluated, although dogs in the heart disease group were significantly older with higher American Society of Anesthesiologists scores. Midazolam and etomidate were used more frequently, and alpha-2 agonists used less frequently, in the heart disease group compared to controls. This study suggests dogs with heart disease, when anesthetized by trained personnel and carefully monitored during routine dental procedures, are not at significantly increased risk for anesthetic complications.}, number={4}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Carter, Jennifer E. and Motsinger-Reif, Alison A. and Krug, William V. and Keene, Bruce W.}, year={2017}, pages={206–213} } @article{mclaughlin_ward_keene_2016, title={Development of a Veterinary Surgical Checklist}, volume={24}, ISSN={1064-8046}, url={http://dx.doi.org/10.1177/1064804615621411}, DOI={10.1177/1064804615621411}, abstractNote={ We describe a new surgical checklist for veterinary cardiologists based on the literature and the application of human factors design. The checklist was developed and iterated with subject-matter experts and was implemented for 4 months, during which use of the checklist was monitored, feedback was gathered, and a final survey was distributed to assess subjective experiences. Although developed for the cardiology team, the checklist also affected the anesthesia team by requiring information and responses to be transmitted across teams. Interviews, subjective reports, and observations pointed to the fact that the checklist engendered communication, particularly by requiring the thoughts and expectations of team members to be stated explicitly. }, number={4}, journal={Ergonomics in Design: The Quarterly of Human Factors Applications}, publisher={SAGE Publications}, author={McLaughlin, Anne Collins and Ward, Jessica and Keene, Bruce W.}, year={2016}, month={Aug}, pages={27–34} } @article{boswood_haggstrom_gordon_wess_stepien_oyama_keene_bonagura_macdonald_patteson_et al._2016, title={Effect of Pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: The EPIC study-a randomized clinical trial}, volume={30}, number={6}, journal={Journal of Veterinary Internal Medicine}, author={Boswood, A. and Haggstrom, J. and Gordon, S. G. and Wess, G. and Stepien, R. L. and Oyama, M. A. and Keene, B. W. and Bonagura, J. and MacDonald, K. A. and Patteson, M. and et al.}, year={2016}, pages={1765–1779} } @article{palerme_jones_ward_balakrishnan_linder_breitschwerdt_keene_2016, title={Infective endocarditis in 13 cats}, volume={18}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/J.JVC.2016.04.003}, DOI={10.1016/J.JVC.2016.04.003}, abstractNote={To describe the clinical presentation, clinicopathological abnormalities and outcomes of a series of cats diagnosed with infective endocarditis (IE) at two tertiary care referral institutions. Thirteen client-owned cats presenting to the cardiology or emergency services of tertiary referral institutions with a diagnosis of endocarditis based on the modified Duke criteria. Retrospective case series. Medical records were reviewed to extract relevant data. In addition, cases that had cardiac tissue available were evaluated by polymerase chain reaction for the presence of Bartonella DNA. Prevalence of feline IE was 0.007%. Cats with endocarditis tended to be older (median age: 9 years, range: 2–12 years) and no sex or breed was overrepresented. Commonly encountered clinical signs included respiratory distress (n = 5) and locomotor abnormalities of varying severity (n = 5). Echocardiographic examination detected valvular lesions consistent with endocarditis on the aortic (n = 8) or mitral (n = 5) valves. Nine cats were diagnosed with congestive heart failure at the time of endocarditis diagnosis. Overall, prognosis was grave with a median survival time of 31 days. In contrast to dogs, cats with IE typically present with clinical signs consistent with cardiac decompensation and locomotor abnormalities suggestive of either thromboembolic disease or inflammatory arthritis. Given the advanced state of disease when diagnosis typically occurs, prognosis is grave.}, number={3}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Palerme, Jean-Sébastien and Jones, Ashley E. and Ward, Jessica L. and Balakrishnan, Nandhakumar and Linder, Keith E. and Breitschwerdt, Edward B. and Keene, Bruce W.}, year={2016}, month={Sep}, pages={213–225} } @article{ward_defrancesco_tou_atkins_griffith_keene_2016, title={Outcome and survival in canine sick sinus syndrome and sinus node dysfunction: 93 cases (2002-2014)}, volume={18}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2016.04.004}, abstractNote={To evaluate the clinical presentation, diagnosis, treatment, and outcomes of a group of dogs with sinoatrial node abnormalities.Ninety-three client-owned dogs at a referral institution.Medical records were reviewed for clinical history, diagnostic testing, and medical or permanent artificial pacemaker (PAP) treatment. Owners or veterinarians were contacted for long-term follow-up.Sixty-one dogs were symptomatic for their bradyarrhythmia and were diagnosed with sick sinus syndrome (SSS). Thirty-two dogs were asymptomatic for their bradyarrhythmia and were diagnosed with sinus node dysfunction (SND). Miniature Schnauzers, West Highland White terriers, Cocker spaniels, and female dogs were overrepresented. Medical management with positive chronotropic drugs successfully controlled syncope long-term in 54% of SSS dogs, and acted as a bridge to PAP in 20%. Positive atropine response predicted medical treatment success. Forty-six percent of SSS dogs eventually underwent PAP implantation. Median survival time was approximately 18 months in SND and SSS dogs regardless of treatment strategy. Congestive heart failure (CHF) associated with progressive valvular heart disease occurred commonly in all groups, particularly in dogs with bradycardia-tachycardia syndrome.Sinus node dysfunction and SSS represent a spectrum of sinoatrial node disease, which for some dogs may also involve a component of autonomic dysfunction. Dogs with SND do not require treatment. Dogs with SSS often require treatment to reduce the frequency of syncope; medical management is often useful, particularly in atropine responsive dogs. Prognosis of SSS with treatment is good, though development of CHF does not appear to be mitigated by treatment.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Ward, J. L. and DeFrancesco, T. C. and Tou, S. P. and Atkins, C. E. and Griffith, E. H. and Keene, B. W.}, year={2016}, month={Sep}, pages={199–212} } @article{balakrishnan_alexander_keene_kolluru_fauls_rawdon_breitschwerdt_2016, title={Successful treatment of mitral valve endocarditis in a dog associated with 'Actinomyces canis-like' infection}, volume={18}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2016.04.005}, abstractNote={Infective endocarditis, an inflammation of the endocardial surface due to invasion by an infectious agent, is more common in middle sized to large breed dogs. We herein report a case of mitral valve endocarditis in a 9-year-old male-castrated Weimaraner caused by an Actinomyces canis-like bacterium, not previously reported in association with infection in dogs.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Balakrishnan, N. and Alexander, K. and Keene, B. and Kolluru, S. and Fauls, M. L. and Rawdon, I. and Breitschwerdt, E. B.}, year={2016}, month={Sep}, pages={271–277} } @article{schneider_coleman_guo_tou_keene_kornegay_2016, title={Suspected acute myocardial infarction in a dystrophin-deficient dog}, volume={26}, ISSN={["1873-2364"]}, DOI={10.1016/j.nmd.2016.02.005}, abstractNote={Golden retriever muscular dystrophy (GRMD) is a model for the genetically homologous human disease, Duchenne muscular dystrophy (DMD). Unlike the mildly affected mdx mouse, GRMD recapitulates the severe DMD phenotype. In addition to skeletal muscle involvement, DMD boys develop cardiomyopathy. While the cardiomyopathy of DMD is typically slowly progressive, rare early episodes of acute cardiac decompensation, compatible with myocardial infarction, have been described. We report here a 7-month-old GRMD dog with an apparent analogous episode of myocardial infarction. The dog presented with acute signs of cardiac disease, including tachyarrhythmia, supraventricular premature complexes, and femoral pulse deficits. Serum cardiac biomarkers, cardiac-specific troponin I (cTnI) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), were markedly increased. Echocardiography showed areas of hyperechoic myocardial enhancement, typical of GRMD cardiomyopathy. Left ventricular dyskinesis and elevated cTnI were suggestive of acute myocardial damage/infarction. Over a 3-year period, progression to a severe dilated phenotype was observed.}, number={6}, journal={NEUROMUSCULAR DISORDERS}, author={Schneider, Sarah Morar and Coleman, Amanda Erickson and Guo, Lee-Jae and Tou, Sandra and Keene, Bruce W. and Kornegay, Joe N.}, year={2016}, month={Jun}, pages={361–366} } @article{friedenberg_chdid_keene_sherry_motsinger-reif_meurs_2016, title={Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.7.693}, abstractNote={Abstract OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM). ANIMALS 8 dogs with and 5 dogs without DCM. PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM. RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Friedenberg, Steven G. and Chdid, Lhoucine and Keene, Bruce and Sherry, Barbara and Motsinger-Reif, Alison and Meurs, Kathryn M.}, year={2016}, month={Jul}, pages={693–699} } @article{hensley_andrade_keene_meurs_tang_wang_caranasos_piedrahita_li_cheng_et al._2015, title={Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts}, volume={19}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.12585}, DOI={10.1111/jcmm.12585}, abstractNote={AbstractThe regenerative potential of cardiosphere‐derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin‐induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM.}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, M. T. and Andrade, J. and Keene, B. and Meurs, Kathryn and Tang, J. N. and Wang, Z. G. and Caranasos, T. G. and Piedrahita, J. and Li, T. S. and Cheng, K. and et al.}, year={2015}, month={Apr}, pages={1805–1813} } @article{ward_defrancesco_tou_atkins_griffith_keene_2015, title={Complication Rates Associated with Transvenous Pacemaker Implantation in Dogs with High-Grade Atrioventricular Block Performed During versus After Normal Business Hours}, volume={29}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12512}, abstractNote={BackgroundTransvenous pacemaker implantation in dogs is associated with a relatively high complication rate. At our institution, pacemaker implantation in dogs with high‐grade atrioventricular block (HG‐AVB) frequently is performed as an after‐hours emergency.HypothesisAmong dogs with HG‐AVB, the rate of major complications is higher when pacemakers are implanted after hours (AH) compared to during business hours (BH).AnimalsClient‐owned dogs with HG‐AVB that underwent transvenous pacemaker implantation between January 2002 and December 2012 at the North Carolina State University Veterinary Teaching Hospital.MethodsRetrospective medical record review. Two‐year follow‐up was required for complications analysis.ResultsMajor complications occurred in 14/79 dogs (18%) and included lead dislodgement, lead or generator infection, lead or generator migration, and pacing failure. Incidence of major complications was significantly higher AH (10/36, 28%) compared to BH (4/43, 9%; P = .041), and all infectious complications occurred AH. Median survival time for all dogs was 27 months and did not differ between AH and BH groups for either all‐cause (P = .70) or cardiac (P = .40) mortality. AH dogs were younger than BH dogs (P = .010), but there were no other clinically relevant differences between BH and AH groups in terms of demographic, clinical, or procedural variables.Conclusions and Clinical ImportanceAt our institution, AH transvenous pacemaker placement is associated with a higher rate of major complications (especially infections) compared to BH placement. This difference may be because of a variety of human factor differences AH versus BH.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Ward, J. L. and DeFrancesco, T. C. and Tou, S. P. and Atkins, C. E. and Griffith, E. H. and Keene, B. W.}, year={2015}, pages={157–163} } @article{keene_tou_2015, title={Cor triatriatum}, journal={Veterinary Image-Guided Interventions}, author={Keene, B. W. and Tou, S. P.}, year={2015}, pages={604–609} } @article{meurs_stern_reina-doreste_maran_chdid_lahmers_keene_mealey_2015, title={Impact of the canine double-deletion beta 1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a beta 1-selective beta-blocker}, volume={25}, ISSN={["1744-6880"]}, url={https://doi.org/10.1097/FPC.0000000000000152}, DOI={10.1097/fpc.0000000000000152}, abstractNote={Objective &bgr;-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene. We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the &bgr;-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs. Methods Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14–21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling. Results Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower). Conclusion ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.}, number={9}, journal={PHARMACOGENETICS AND GENOMICS}, author={Meurs, Kathryn M. and Stern, Josh A. and Reina-Doreste, Yamir and Maran, Brian A. and Chdid, Lhoucine and Lahmers, Sunshine and Keene, Bruce W. and Mealey, Katrina L.}, year={2015}, month={Sep}, pages={427–431} } @article{hogan_fox_jacob_keene_laste_rosenthal_sederquist_weng_2015, title={Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT)}, volume={17}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2015.10.004}, abstractNote={To determine if clopidogrel administration is associated with a reduced likelihood of recurrent cardiogenic arterial thromboembolism (CATE) in cats compared to aspirin administration. Secondary aims were to determine if clopidogrel administration had an effect on the composite endpoint of recurrent CATE and cardiac death and to identify adverse effects of chronic clopidogrel or aspirin therapy. Seventy-five cats that survived a CATE event. Multicenter, double-blind, randomized, positive-controlled study. Cats were assigned to clopidogrel (18.75 mg/cat PO q 24 h) or aspirin (81 mg/cat PO q 72 h). Kaplan–Meier survival curves were created for each endpoint and the log rank test performed to compare treatment groups with respect to time to event and the likelihood of the event occurring. The mean age of all cats was 8.0 ± 3.5 yr and 57/75 (76%) were male (p < 0.001); 62/75 (83%) were mixed breed with the remainder including Persian, Abyssinian, American Shorthair, Bengal, Birman, Himalayan, Maine Coon, Ragdoll, Snowshoe, and Sphynx breeds. Only 15% (11/75) of cats had a history of heart disease recorded prior to the CATE event. Clopidogrel administration was associated with significantly reduced likelihood of recurrent CATE compared to aspirin (p = 0.024) and had a longer median time to recurrence [443 (95% CI 185–990) days vs. 192 (95% CI 62–364) days, respectively]. Clopidogrel was also associated with a significantly reduced likelihood of the composite endpoint of recurrent CATE or cardiac death (p = 0.033) with a longer median time to event [346 (95% CI 146–495) days vs. 128 (95% CI 58–243) days]. Clopidogrel administration significantly reduces the likelihood of recurrent CATE compared with aspirin in cats; both drugs were well tolerated.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Hogan, Daniel F. and Fox, Philip R. and Jacob, Kristin and Keene, Bruce and Laste, Nancy J. and Rosenthal, Steven and Sederquist, Kimberly and Weng, Hsin-Yi}, year={2015}, month={Dec}, pages={S306–S317} } @article{oura_young_keene_robertson_jennings_thrall_2015, title={A VALENTINE-SHAPED CARDIAC SILHOUETTE IN FELINE THORACIC RADIOGRAPHS IS PRIMARILY DUE TO LEFT ATRIAL ENLARGEMENT}, volume={56}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12221}, abstractNote={Conflicting information has been published regarding the cause of a valentine‐shaped cardiac silhouette in dorsoventral or ventrodorsal thoracic radiographs in cats. The purpose of this retrospective, cross‐sectional study was to test the hypothesis that the valentine shape is primarily due to left atrial enlargement. Images for cats with a radiographic valentine‐shaped cardiac silhouette and full echocardiography examination were retrieved and independently reviewed. A subjective scoring system was used to record severity of radiographic valentine shape. Subjective radiographic evidence of left atrial enlargement in a radiographic lateral projection and a final diagnosis based on medical records were also recorded. A total of 81 cats met inclusion criteria. There was a strong positive correlation (P < 0.001) between echocardiographic left atrial size and severity of radiographic valentine shape. There was no effect of echocardiographic right atrial size on the severity of valentine shape, except when concurrent with severe left atrial enlargement. In this situation, right atrial enlargement increased the likelihood of observing a severe valentine shape. There was no effect of right atrial enlargement on the shape of the cardiac silhouette when left atrial enlargement was absent or only mild to moderate. There was no correlation between the category of final diagnosis of cardiac disease and the severity of valentine shape. Findings from this study supported the hypothesis that a valentine‐shaped cardiac silhouette in radiographs is due primarily to left atrial enlargement in cats, with right atrial enlargement only impacting the shape if concurrent with severe left atrial enlargement.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Oura, Trisha J. and Young, Aisha N. and Keene, Bruce W. and Robertson, Ian D. and Jennings, Dennis E. and Thrall, Donald E.}, year={2015}, pages={245–250} } @article{lantis_ames_atkins_defrancesco_keene_werre_2015, title={Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs}, volume={38}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12154}, abstractNote={Pilot studies in our laboratory revealed that furosemide‐induced renin‐angiotensin‐aldosterone system (RAAS) activation was not attenuated by the subsequent co‐administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin‐converting enzyme (ACE) activity and furosemide‐induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide‐induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4–6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days −1, −2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days −1 and −2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P < 0.05). Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P < 0.05) but did not significantly reduce aldosterone excretion (Group FB baseline UAldo:C = 0.35, SD 0.16; day 1 UAldo:C = 0.79, SD 0.39; day 3 UAldo:C 0.92, SD 0.48, day 7 UAldo:C = 0.99, SD 0.48, P < 0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide‐induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lantis, A. C. and Ames, M. K. and Atkins, C. E. and Defrancesco, T. C. and Keene, B. W. and Werre, S. R.}, year={2015}, month={Feb}, pages={65–73} } @article{reina-doreste_stern_keene_tou_atkins_defrancesco_ames_hodge_meurs_2014, title={Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure}, volume={245}, ISSN={["1943-569X"]}, url={https://doi.org/10.2460/javma.245.5.534}, DOI={10.2460/javma.245.5.534}, abstractNote={Abstract Objective—To assess survival time and adverse events related to the administration of pimobendan to cats with congestive heart failure (CHF) secondary to hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM). Design—Retrospective case-control study. Animals—27 cats receiving treatment with pimobendan and 27 cats receiving treatment without pimobendan. Procedures—Medical records between 2003 and 2013 were reviewed. All cats with HCM or HOCM treated with a regimen that included pimobendan (case cats) were identified. Control cats (cats with CHF treated during the same period with a regimen that did not include pimobendan) were selected by matching to case cats on the basis of age, sex, body weight, type of cardiomyopathy, and manifestation of CHF. Data collected included signalment, physical examination findings, echocardiographic data, serum biochemical values, and survival time from initial diagnosis of CHF. Kaplan-Meier survival curves were constructed and compared by means of a log rank test. Results—Cats receiving pimobendan had a significant benefit in survival time. Median survival time of case cats receiving pimobendan was 626 days, whereas median survival time for control cats not receiving pimobendan was 103 days. No significant differences were detected for any other variable. Conclusions and Clinical Relevance—The addition of pimobendan to traditional treatment for CHF may provide a substantial clinical benefit in survival time for HCM-affected cats with CHF and possibly HOCM-affected cats with CHF.}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Reina-Doreste, Yamir and Stern, Joshua A. and Keene, Bruce W. and Tou, Sandra P. and Atkins, Clarke E. and DeFrancesco, Teresa C. and Ames, Marisa K. and Hodge, Timothy E. and Meurs, Kathryn M.}, year={2014}, month={Sep}, pages={534–539} } @article{edwards_coleman_brainard_defrancesco_hansen_keene_koenig_2014, title={Outcome of positive-pressure ventilation in dogs and cats with congestive heart failure: 16 cases (1992-2012)}, volume={24}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12230}, abstractNote={AbstractObjectiveTo describe the indications, duration of ventilation, underlying cardiac diseases, and outcome of dogs and cats undergoing positive‐pressure ventilation (PPV) for treatment of congestive heart failure (CHF).DesignTwo‐site retrospective study (1992–2012).SettingTwo university small animal teaching hospitals.AnimalsSix cats and 10 dogs undergoing PPV for CHF.InterventionsNone.Measurements and Main ResultsMedical records were searched to identify patients requiring PPV for treatment of pulmonary edema secondary to CHF. Sixteen animals fulfilled these criteria. Patient signalment, duration of PPV, underlying cardiac disease, arterial or venous blood gas values, pharmacologic therapy before, during, and after PPV, anesthetic drugs, complications, and outcome were recorded. Overall survival to discharge was 62.5% (10/16). Mean (±SD) duration of PPV was 30.8 ± 21.3 hours and average time from presentation for CHF to initiation of PPV was 5.9 ± 6.4 hours. Azotemia at the time of initiation of ventilation, development of anuria or oliguria, and use of pentobarbital for anesthesia were negatively associated with survival (P = 0.011, P = 0.036, and P = 0.036, respectively). Survival‐to‐discharge rate was 77% (10/13) for patients treated after 2005 and those not receiving pentobarbital. There was no significant effect attributed to age, sex, weight, species, nature of heart disease, furosemide dose, length of ventilation, use of vasopressors, first‐time CHF events, or plasma lactate concentration on survival to discharge.ConclusionsDogs and cats requiring PPV for CHF have a good overall prognosis for hospital discharge and require PPV for a relatively short duration. Azotemia, oliguria or anuria, and the use of pentobarbital are negatively associated with outcome.}, number={5}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Edwards, Thomas H. and Coleman, Amanda Erickson and Brainard, Benjamin M. and DeFrancesco, Teresa C. and Hansen, Bernard D. and Keene, Bruce W. and Koenig, Amie}, year={2014}, pages={586–593} } @article{meurs_stern_sisson_kittleson_cunningham_ames_atkins_defrancesco_hodge_keene_et al._2013, title={Association of Dilated Cardiomyopathy with the Striatin Mutation Genotype in Boxer Dogs}, volume={27}, ISSN={["1939-1676"]}, url={https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvim.12163}, DOI={10.1111/jvim.12163}, abstractNote={BackgroundMyocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families.Hypothesis/ObjectivesWe hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion.AnimalsThirty‐three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease.MethodsDNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T‐tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%.ResultsThirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements.Conclusions and Clinical ImportanceThis study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Meurs, K. M. and Stern, J. A. and Sisson, D. D. and Kittleson, M. D. and Cunningham, S. M. and Ames, M. K. and Atkins, C. E. and DeFrancesco, T. and Hodge, T. E. and Keene, B. W. and et al.}, year={2013}, month={Nov}, pages={1437–1440} } @article{stern_tou_barker_hill_lodge_mathews_keene_2013, title={Hybrid cutting balloon dilatation for treatment of cor triatriatum sinister in a cat}, volume={15}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2013.03.001}, DOI={10.1016/j.jvc.2013.03.001}, abstractNote={A hybrid surgical approach and balloon dilatation were performed successfully in a cat with cor triatriatum sinister and clinical signs of congestive heart failure. Left lateral thoracotomy was used to access the heart and cutting balloon followed by standard balloon dilatation were utilized to dilate the perforation in the anomalous left atrial membrane. Clinical signs resolved completely after dilation of the anomalous left atrial membrane. Based upon the outcome of this case, balloon dilatation appears to be a viable treatment option for cats affected with cor triatriatum sinister.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Stern, Joshua A. and Tou, Sandra P. and Barker, Piers C. A. and Hill, Kevin D. and Lodge, Andrew J. and Mathews, Kyle G. and Keene, Bruce W.}, year={2013}, month={Sep}, pages={205–210} } @article{visser_keene_mathews_browne_chanoit_2013, title={Outcomes and Complications Associated With Epicardial Pacemakers in 28 Dogs and 5 Cats}, volume={42}, ISSN={["1532-950X"]}, DOI={10.1111/j.1532-950x.2013.12020.x}, abstractNote={AbstractObjectiveTo report signalment, history, indications, complications and outcome for 28 dogs and 5 cats in which 34 permanent epicardial pacing leads were surgically placed by transdiaphragmatic approach (32) or intercostal thoracotomy (2).MethodsMedical records (2005–2010) were reviewed. Signalment, age, species, gender, clinical signs, presence of structural heart disease and/or congestive heart failure, ECG diagnosis, body weight (<10 or >10 kg), and overall survival rate were recorded. Statistical correlations were made between these variables and major and minor complications rates.ResultsExcept for body weight, no statistical differences were identified in prevalence of major (life threatening or requiring replacement of the pacemaker system) or minor (self‐limiting) complications; dogs weighing >10 kg had significantly more major complications (P = .03). There was a trend (P = .051) for lower survival in animals that had major complications.ConclusionsLarger dogs (>10 kg) may be predisposed to more major complications with epicardial pacemaker (EP) implantation. Major complication rate and survival time are similar to those reported for transvenous pacing and therefore implantation of EPs remains a suitable alternative.}, number={5}, journal={VETERINARY SURGERY}, author={Visser, Lance C. and Keene, Bruce W. and Mathews, Kyle G. and Browne, William J. and Chanoit, Guillaume}, year={2013}, month={Jun}, pages={544–550} } @article{meurs_lahmers_keene_white_oyama_mauceli_lindblad-toh_2012, title={A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher}, volume={131}, ISSN={["1432-1203"]}, DOI={10.1007/s00439-012-1158-2}, abstractNote={Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p < 0.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.}, number={8}, journal={HUMAN GENETICS}, author={Meurs, Kathryn M. and Lahmers, Sunshine and Keene, Bruce W. and White, Stephen N. and Oyama, Mark A. and Mauceli, Evan and Lindblad-Toh, Kerstin}, year={2012}, month={Aug}, pages={1319–1325} } @article{kornegay_bogan_bogan_childers_li_nghiem_detwiler_larsen_grange_bhavaraju-sanka_et al._2012, title={Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies}, volume={23}, number={1-2}, journal={Mammalian Genome}, author={Kornegay, J. N. and Bogan, J. R. and Bogan, D. J. and Childers, M. K. and Li, J. and Nghiem, P. and Detwiler, D. A. and Larsen, C. A. and Grange, R. W. and Bhavaraju-Sanka, R. K. and et al.}, year={2012}, pages={85–108} } @article{kane_defrancesco_boyle_malarkey_ritchey_atkins_cullen_kornegay_keene_2013, title={Cardiac structure and function in female carrier's of a canine model of Duchenne muscular dystrophy}, volume={94}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2012.09.027}, abstractNote={This investigation tested the hypothesis that carriers of golden retriever muscular dystrophy (GRMD), a genetically homologous condition of Duchenne muscular dystrophy (DMD), have quantifiable abnormalities in myocardial function, structure, or cardiac rhythm. Eleven GRMD carriers and four matched controls had cardiac evaluations and postmortem examinations. 24-h ECG Holter monitoring disclosed ventricular ectopy in 10 of 11 carriers and 2 of 4 controls. Conventional echocardiography failed to demonstrate significant differences between carriers and controls in systolic function. All carriers had multifocal, minimal to marked myofiber necrosis, fibrosis, mineralization, inflammation, and/or fatty change in their hearts. Immunohistochemistry revealed a mosaic dystrophin deficiency in scattered cardiac myofibers in all carriers. No controls had cardiac histologic lesions; all had uniform dystrophin staining. Despite cardiac mosaic dystrophin expression and degenerative cardiac lesions, GRMD carriers at up to 3 years of age could not be distinguished statistically from normal controls by echocardiography or 24-h Holter monitoring.}, number={3}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Kane, A. M. and DeFrancesco, T. C. and Boyle, M. C. and Malarkey, D. E. and Ritchey, J. W. and Atkins, C. E. and Cullen, J. M. and Kornegay, J. N. and Keene, B. W.}, year={2013}, month={Jun}, pages={610–617} } @article{stern_tobias_keene_2012, title={Complete atrioventricular block secondary to cardiac lymphoma in a dog}, volume={14}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2012.04.007}, DOI={10.1016/j.jvc.2012.04.007}, abstractNote={Third degree atrioventricular (AV) block was observed in a patient with a roughly spherical mass measuring approximately 1 × 1 × 1 cm, visible in the basilar portion of the interventricular septum on 2-dimensional transthoracic echocardiographic examination. The patient had a brief history of lethargy and episodic collapse, and the owner elected to euthanize the dog after the mass lesion was discovered. Necropsy revealed multiple masses within the interventricular septum, ventricular free walls and atrial myocardium. The final diagnosis was large cell (T-cell) lymphosarcoma.}, number={4}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Stern, Joshua A. and Tobias, Jeremy R. and Keene, Bruce W.}, year={2012}, month={Dec}, pages={537–539} } @article{leblanc_defrancesco_adams_atkins_tou_fudge_keene_2012, title={Cutting balloon catheterization for interventional treatment of cor triatriatum dexter: 2 Cases}, volume={14}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2012.04.006}, DOI={10.1016/j.jvc.2012.04.006}, abstractNote={Cutting balloon dilatation was performed successfully in two dogs with cor triatriatum dexter and clinical signs of ascites. The cutting balloon catheter uses incisional microtomes embedded in a balloon catheter. During balloon expansion, these microtomes incise the adjacent tissue, decreasing circumferential wall stress. This theoretically reduces both the likelihood of fracturing the adjacent tissues in an uncontrolled manner and the potential neoproliferative response to standard balloon dilatation and the subsequent incidence of re-stenosis. In both cases described, clinical signs resolved completely following cutting balloon dilatation of the anomalous membrane. Based on the outcome of these 2 cases, cutting balloon dilatation appears to be a viable treatment option for dogs affected with cor triatriatum dexter.}, number={4}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={LeBlanc, Nicole and DeFrancesco, Teresa C. and Adams, Allison K. and Atkins, Clark E. and Tou, Sandra P. and Fudge, James Curt and Keene, Bruce W.}, year={2012}, month={Dec}, pages={525–530} } @article{chanoit_mathews_keene_small_linder_2012, title={Surgical treatment of a pulmonary artery vascular hamartoma in a dog}, volume={240}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.240.7.858}, DOI={10.2460/javma.240.7.858}, abstractNote={Abstract Case Description—A 6-year-old Siberian Husky–mix dog was examined for episodes of collapse. Clinical Findings—Physical examination, echocardiography, abdominal ultrasonography, ECG, and thoracic computed tomography with contrast were performed and revealed a 2.5 × 2.3 × 2.0-cm mass over the pulmonic valve leaflets, resulting in moderate pulmonic stenosis. Other abnormal findings included systemic hypertension, right bundle branch block, proteinuria, and a urinary bladder mass. Treatment and Outcome—Pulmonary arteriotomy was performed under inflow occlusion, and the mass was resected with transesophageal echocardiographic guidance and direct visualization. Results of histologic examination of the mass revealed a vascular hamartoma. Sequential follow-up examinations and telephone contacts (at 0.5, 5, and 15 months after surgery) revealed that the patient had been free from episodes of collapse since surgery. No regrowth of the mass was noted on follow-up echocardiograms, and the pulmonic stenosis had resolved, although mild to moderate pulmonary insufficiency later developed. The bladder mass was excised 15 months after the first surgery when hematuria developed, and results of histologic examination of this mass revealed a vascular hamartoma. The dog was eventually euthanized 31 months after the initial surgery for reasons that could not be directly linked to any recurrence of the pulmonary artery mass. Clinical Relevance—Hamartomas are benign tumors that can be located in various tissues, including large arteries. Computed tomography was helpful in predicting the resectability of the intracardiac mass in this dog. Treatment with arteriotomy under inflow occlusion and mild hypothermia resulted in a favorable outcome.}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Chanoit, Guillaume and Mathews, Kyle G. and Keene, Bruce W. and Small, Merrilee T. and Linder, Keith}, year={2012}, month={Apr}, pages={858–862} } @article{tou_defrancesco_keene_2011, title={ECG of the Month}, volume={239}, ISSN={["1943-569X"]}, DOI={10.2460/javma.239.1.55}, number={1}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tou, Sandra P. and DeFrancesco, Teresa C. and Keene, Bruce W.}, year={2011}, month={Jul}, pages={55–57} } @article{fox_rush_reynolds_defrancesco_keene_atkins_gordon_schober_bonagura_stepien_et al._2011, title={Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for Asymptomatic (occult) Cardiomyopathy in Cats}, volume={25}, number={5}, journal={Journal of Veterinary Internal Medicine}, author={Fox, P. R. and Rush, J. E. and Reynolds, C. A. and DeFrancesco, T. C. and Keene, B. W. and Atkins, C. E. and Gordon, S. G. and Schober, K. E. and Bonagura, J. D. and Stepien, R. L. and et al.}, year={2011}, pages={1010–1016} } @article{tou_keene_barker_2011, title={Pulmonary atresia and ventricular septal defect with aortopulmonary collaterals in an adult dog}, volume={13}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2011.09.002}, DOI={10.1016/j.jvc.2011.09.002}, abstractNote={Pulmonary atresia and ventricular septal defect (PA-VSD) was diagnosed in a 2-year-old castrated male Terrier mix. Transthoracic echocardiography identified a large ventricular septal defect, overriding aorta and severe right ventricular hypertrophy. A main pulmonary artery could not be identified, consistent with pulmonary atresia or persistent truncus arteriosus. Transesophageal echocardiography and angiography confirmed PA-VSD with aortopulmonary collateral circulation arising from the descending thoracic aorta. This case report describes the antemortem diagnosis of the rare congenital defect PA-VSD in an adult dog.}, number={4}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Tou, Sandra P. and Keene, Bruce W. and Barker, Piers C.A.}, year={2011}, month={Dec}, pages={271–275} } @article{perez_hummel_keene_maggi_diniz_breitschwerdt_2010, title={Successful treatment ofBartonella henselaeendocarditis in a cat}, volume={12}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1016/j.jfms.2009.12.018}, DOI={10.1016/j.jfms.2009.12.018}, abstractNote={This report describes the clinical presentation, diagnosis and treatment of a cat with vegetative valvular endocarditis temporally associated with natural infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the main clinical signs that resulted in referral for diagnostic evaluation. Using a novel and sensitive culture approach, B henselae was isolated from the blood. Following antibiotic therapy there was total resolution of clinical signs, the heart murmur, the valvular lesion by echocardiography, and no Bartonella species was isolated or amplified from a post-treatment blood culture. In conjunction with previous case reports, infective endocarditis can be associated with natural B henselae infection in cats; however, early diagnosis and treatment may result in a better prognosis than previously reported.}, number={6}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Perez, Cristina and Hummel, James B. and Keene, Bruce W. and Maggi, Ricardo G. and Diniz, Pedro P.V.P. and Breitschwerdt, Edward B.}, year={2010}, month={Jun}, pages={483–486} } @article{sayer_atkins_fujii_adams_defrancesco_keene_2009, title={Acute Effect of Pimobendan and Furosemide on the Circulating Renin-Angiotensin-Aldosterone System in Healthy Dogs}, volume={23}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2009.0367.x}, abstractNote={Background:The renin‐angiotensin‐aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators.Hypothesis:Short‐term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide.Animals:Nine healthy laboratory dogs were used in this study.Methods:Experimental, cross‐over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash‐out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle.Results:There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6).Conclusions and Clinical Relevance:Short‐term administration of high‐dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Sayer, M. B. and Atkins, C. E. and Fujii, Y. and Adams, A. K. and DeFrancesco, T. C. and Keene, B. W.}, year={2009}, pages={1003–1006} } @misc{atkins_bonagura_ettinger_fox_gordon_haggstrom_hamlin_keene_luis-fuentes_stepien_2009, title={Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease}, volume={23}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70350430448&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2009.0392.x}, abstractNote={his is the report of the American College of Veteri-nary Internal Medicine (ACVIM) Specialty ofCardiology consensus panel convened to formulateguidelines forthe diagnosis andtreatment ofchronicval-vularheartdisease (CVHD, also knownas endocardiosisand myxomatous valve degeneration) in dogs. It is esti-mated that approximately 10% of dogs presented toprimary care veterinary practices have heart disease, andCVHD is the most common heart disease of dogs inmany parts of the world, accounting for approximately75% of canine cases of heart disease cases seen by veter-inary practices in North America.CVHD most commonly affects the left atrioventricu-lar or mitral valve, although in approximately 30% ofcases the right atrioventricular (tricuspid) valve also isinvolved. The disease is approximately 1.5 times morecommon in males than in females. Its prevalence is alsohigher in smaller (o20kg) dogs, although large breedsoccasionally are affected.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Atkins, C. and Bonagura, J. and Ettinger, S. and Fox, P. and Gordon, S. and Haggstrom, J. and Hamlin, R. and Keene, B. and Luis-Fuentes, V. and Stepien, R.}, year={2009}, pages={1142–1150} } @article{fox_oyama_reynolds_rush_defrancesco_keene_atkins_macdonald_schober_bonagura_et al._2009, title={Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats}, volume={11}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2008.12.001}, DOI={10.1016/j.jvc.2008.12.001}, abstractNote={Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/Ea). NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis. NT-proBNP (1) was higher (median and inter-quartile [25th–75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P < 0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (ρ = 0.266; P = 0.007) and LV free wall thickness (ρ = 0.218; P = 0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/Ea ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94). NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.}, number={Supplement 1}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Fox, Philip R. and Oyama, Mark A. and Reynolds, Caryn and Rush, John E. and DeFrancesco, Terri C. and Keene, Bruce W. and Atkins, Clark E. and MacDonald, Kristin A. and Schober, Karsten E. and Bonagura, John D. and et al.}, year={2009}, month={May}, pages={S51–S61} } @article{beddies_fox_papich_kanikanti_krebber_keene_2008, title={Comparison of the pharmacokinetic properties of bisoprolol and carvedilol in healthy dogs}, volume={69}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.69.12.1659}, abstractNote={Abstract Objective—To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation β1-adrenoceptor–selective blocking agent, with those of carvedilol, a third-generation β1/β2 and α1-adrenoceptor blocking agent, in dogs. Animals—12 healthy adult Beagles. Procedures—A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed. Results—After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 μg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 μg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 μg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 μg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol. Conclusions and Clinical Relevance—After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Beddies, Gerald and Fox, Philip R. and Papich, Mark D. and Kanikanti, Venkata-Rangaro and Krebber, Ralph and Keene, Bruce W.}, year={2008}, month={Dec}, pages={1659–1663} } @article{cunha_buccellato_keene_rajala-schultz_nishijima_ozkanlar_hamlin_2008, title={Electrocardiographic, hematologic, histopathologic, and recovery characteristics from repeated morphine-chloralose anesthesia in dogs}, volume={6}, number={3}, journal={International Journal of Applied Research in Veterinary Medicine}, author={Cunha, D. N. Q. and Buccellato, M. and Keene, B. W. and Rajala-Schultz, P. and Nishijima, Y. and Ozkanlar, Y. and Hamlin, R. L.}, year={2008}, pages={191–199} } @article{finster_defrancesco_atkins_hansen_keene_2008, title={Supraventricular tachycardia in dogs: 65 cases (1990-2007)}, volume={18}, ISSN={["1476-4431"]}, DOI={10.1111/j.1476-4431.2008.00346.x}, abstractNote={AbstractObjective –To characterize the signalment, clinical findings, and prognosis of dogs with supraventricular tachycardia (SVT).Design –Retrospective study.Setting –North Carolina State University Veterinary Teaching Hospital.Animals, Intervention, and Measurements –Case selection included all patients at the veterinary teaching hospital with SVT during years 1990–2007. Medical records from dogs with at least 1 recorded episode of SVT were extracted. The signalment, history, electrocardiographic, radiographic, and echocardiographic findings, therapy, and response to therapy were reviewed and summarized. Follow‐up was conducted to determine the date and cause of death. Kaplan‐Meier survival curves were constructed and analyzed. The relationships between patient characteristics and responses to therapy and prognosis were evaluated.Main Results –Sixty‐five records documented a diagnosis of SVT. Sixty‐two percent were males. Labrador Retrievers and Boxers were overrepresented compared with the general hospital population. Median age at presentation was 9 years (range 0.5–15.5 y). The median heart rate during SVT was 270/minute (range 187–375/min). The most common presenting complaint was syncope (30%), 23% were asymptomatic at the time of diagnosis. Most dogs had structural heart disease (65%). Median survival was 472 days (<1–2007 d). Identification of sustained SVT (>30 s) did not affect survival (P=0.50), nor did the presence of congestive heart failure (P=0.70).Conclusions –The majority of dogs with SVT had structural heart disease or a severe concurrent illness at the time of SVT diagnosis. SVT, though often a persistent and occasionally sustained arrhythmia, does not appear to be a primary factor in mortality.}, number={5}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Finster, Sharon T. and DeFrancesco, Teresa C. and Atkins, Clarke E. and Hansen, Bernie D. and Keene, Bruce W.}, year={2008}, month={Oct}, pages={503–510} } @article{small_atkins_gordon_birkenheuer_booth-sayer_keene_fujii_miller_2008, title={Use of a nitinol gooseneck snare catheter for removal of adult Dirofilaria immitis in two cats}, volume={233}, ISSN={["0003-1488"]}, DOI={10.2460/javma.233.9.1441}, abstractNote={Abstract Case Description—2 cats were examined because of congestive heart failure secondary to heartworm infection. Clinical Findings—One cat had severe abdominal distention and the other had dyspnea secondary to chylothorax. Both had loud right-sided heart murmurs, precordial thrills, and jugular distension. Thoracic radiography revealed cardiomegaly and enlarged caudal pulmonary arteries. Echocardiography revealed tricuspid regurgitation and multiple hyperechoic structures consistent with adult Dirofilaria immitis within the right atrium, right ventricle, and main pulmonary artery. Pulmonary hypertension was documented by means of Doppler echocardiography in 1 cat. Treatment and Outcome—Cats were anesthetized, and a nitinol gooseneck snare catheter was introduced into the right side of the heart via a jugular venotomy. In the first cat, the snare was used to retrieve 5 female and 2 male adult D immitis. The catheter was then passed into the main pulmonary artery in an unsuccessful attempt to retrieve remaining heartworms. In the second cat, 2 adult female D immitis were removed from the right atrium with the nitinol snare. In both cats, clinical signs resolved within 4 weeks after the procedure. Clinical Relevance—Findings suggested that use of a nitinol gooseneck snare catheter may be a safe and effective technique for removing adult D immitis from the right atrium and ventricle in cats and that successful removal of adult heartworms in infected cats may resolve clinical signs of right-sided congestive heart failure and chylothorax. In addition, findings in 1 cat suggested that removal of all adult heartworms may not be necessary for clinical signs to resolve.}, number={9}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Small, Merrilee T. and Atkins, Clarke E. and Gordon, Sonya G. and Birkenheuer, Adam J. and Booth-Sayer, Margaret A. and Keene, Bruce W. and Fujii, Yoko and Miller, Matthew W.}, year={2008}, month={Nov}, pages={1441–1445} } @article{wood_vaden_cerda-gonzalez_keene_2007, title={Cystoscopic-guided balloon dilation of a urethral stricture in a female dog}, volume={48}, number={7}, journal={Canadian Veterinary Journal}, author={Wood, M. W. and Vaden, S. and Cerda-Gonzalez, S. and Keene, B.}, year={2007}, pages={731–733} } @article{adams_keene_2007, title={ECG of the month}, volume={231}, ISSN={["0003-1488"]}, DOI={10.2460/javma.231.2.209}, number={2}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Adams, Allison K. and Keene, Bruce W.}, year={2007}, month={Jul}, pages={209–211} } @article{gardner_atkins_rausch_defrancesco_chandler_keene_2007, title={Estimation of 24-h aldosterone secretion in the dog using the urine aldosterone: Creatinine ratio}, volume={9}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2006.11.001}, DOI={10.1016/j.jvc.2006.11.001}, abstractNote={One potential method of evaluating renin–angiotensin–aldosterone system (RAAS) activation involves the quantification of urinary aldosterone excretion. While blood concentrations of aldosterone are easily obtained, results may be misleading because of minute-to-minute variation in aldosterone secretion and subsequent blood concentrations. Urinary aldosterone concentration measurement represents a more consistent "pooled" index of aldosterone secretion, but obtaining 24-h urine samples is time-consuming, difficult, and fraught with potential error. We postulated that the urinary aldosterone:creatinine ratio, measured from spot urine samples, would correlate well with 24-h urinary aldosterone excretion, and would provide a simple index of aldosterone excretion that would eliminate the need for 24-h urine collection. After validating an assay for aldosterone in canine urine, 24-h urinary aldosterone excretion was determined by radioimmunoassay from 8 normal, male beagle dogs under control conditions, after RAAS stimulation with amlodipine administration, and after RAAS attenuation with the addition of enalapril to amlodipine administration. Spot urine samples, each obtained at the same time of day, were used to determine the aldosterone:creatinine ratio during control conditions, RAAS stimulation, and RAAS attenuation. The aldosterone:creatinine ratio from spot-checked urine samples correlated well with 24-h urinary aldosterone excretion (r = 0.77, P < 0.0001). A spot urinary aldosterone:creatinine ratio might be substituted for 24-h urinary aldosterone determination.}, number={1}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Gardner, Sarah Y. and Atkins, Clarke E. and Rausch, William P. and DeFrancesco, Teresa C. and Chandler, Donald Walt and Keene, Bruce W.}, year={2007}, month={May}, pages={1–7} } @article{hansen_lascelles_keene_adams_thomson_2007, title={Evaluation of an accelerometer for at-home monitoring of spontaneous activity in dogs}, volume={68}, ISSN={["0002-9645"]}, url={https://dx.doi.org/10.2460/ajvr.68.5.468}, DOI={10.2460/ajvr.68.5.468}, abstractNote={Abstract Objective—To determine the correlation between activity as measured by an accelerometer and videographic measurements of movement and mobility in healthy dogs. Animals—4 healthy dogs. Procedures—After determination that accelerometers had good agreement, 5 identical accelerometers were used simultaneously to test their output at 8 locations (rotated among collar, vest, and forelimb stocking locations) on each dog. Movement and mobility for each dog were recorded continuously with a computerized videography system for 7-hour ses-sions on 4 consecutive days. Accelerometer values were combined into 439 fifteen-minute intervals and compared with 3 videographic measurements of movement and mobility (distance traveled, time spent walking > 20 cm/s, and time spent changing position by > 12% of 2-dimensional surface area during 1.5 seconds). Results—96% of values compared between the most discordant pair of accelerometers were within 2 SDs of the mean value from all 5 accelerometers. All mounting locations provided acceptable correlation with videographic measurements of movement and mobility, and the ventral portion of the collar was determined to be the most convenient location. Conclusions and Clinical Relevance—Use of an accelerometer was adequate for at-home activity monitoring, an important end point in clinical trials of treatment for chronic disease, and provided information about daily activity that is unattainable by other methods.}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, publisher={American Veterinary Medical Association (AVMA)}, author={Hansen, Bernard D. and Lascelles, Duncan X. and Keene, Bruce W. and Adams, Allison K. and Thomson, Andrea E.}, year={2007}, month={May}, pages={468–475} } @article{kuppinger_fischer_sum_hirschberger_rausch_keene_tippett_schulz_2007, title={Lack of GNB3 exon 9 polymorphism in primary hypertensive and normotensive dogs}, volume={160}, ISSN={["0042-4900"]}, DOI={10.1136/vr.160.19.654}, abstractNote={The 5500T allele variant of the c 5500t single nucleotide polymorphism in the human G protein β3 subunit (gnb3) has been reported to be associated with primary hypertension. In this study, the gnb3 gene of primary hypertensive and normotensive dogs was examined for an analogous nucleotide polymorphism associated with hypertension. The genomic gnb3 dna, with 10 exons and nine introns coding for 340 amino acids, is described. pcr product sequencing of the gnb3 exon 9 from 25 dogs (including five hypertensive animals) failed to detect any nucleotide polymorphism. In contrast to human beings, there was no polymorphism at either the analogous nucleotide or in the respective exon. Only the human hypertension‐associated thymine was detected, regardless of whether the dogs were hypertensive or normotensive. Furthermore, examinations of 565 dogs of 85 distinct breeds for the presence of the human 5500C nucleotide at the analogous nucleotide side failed to detect a cytosine that is present with high allele frequency in normotensive man. Owing to the lack of allele variance, it is concluded that canine primary hypertension is not associated with a polymorphism at either the respective human hypertension‐associated nucleotide site or in the entire exon.}, number={19}, journal={VETERINARY RECORD}, author={Kuppinger, O. and Fischer, E. and Sum, S. and Hirschberger, J. and Rausch, W. P. and Keene, B. W. and Tippett, F. and Schulz, R.}, year={2007}, month={May}, pages={654–657} } @article{defrancesco_rush_rozanski_hansen_keene_moore_atkins_2007, title={Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea}, volume={21}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2007)21[243:PCEOAE]2.0.CO;2}, abstractNote={Background:B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). Hypothesis:The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. Animals:Three hundred and thirty dogs from 2 large university teaching hospitals. Methods:We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. Results:Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) Conclusion and Clinical Importance: Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={DeFrancesco, Teresa C. and Rush, John E. and Rozanski, Elizabeth A. and Hansen, Bernard D. and Keene, Bruce W. and Moore, Dominic T. and Atkins, Clarke E.}, year={2007}, pages={243–250} } @article{atkins_keene_brown_coats_crawford_defrancesco_edwards_fox_lehmkuhl_luethy_et al._2007, title={Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency}, volume={231}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.231.7.1061}, DOI={10.2460/javma.231.7.1061}, abstractNote={Abstract Objective—To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF). Design—Placebo-controlled, double-blind, multicenter, randomized trial. Animals—124 dogs with compensated mitral valve regurgitation (MR). Procedures—Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for ≤ 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days. Results—Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end. Conclusions and Clinical Relevance—Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Atkins, Clarke E. and Keene, Bruce W. and Brown, William A. and Coats, Julie R. and Crawford, Mary Ann and DeFrancesco, Teresa C. and Edwards, N. Joel and Fox, Phillip R. and Lehmkuhl, Linda B. and Luethy, Michael W. and et al.}, year={2007}, month={Oct}, pages={1061–1069} } @article{atkins_rausch_gardner_defrancesco_keene_levine_2007, title={The effect of amlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone system in the dog}, volume={30}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2007.00894.x}, DOI={10.1111/j.1365-2885.2007.00894.x}, abstractNote={Excessive aldosterone secretion is detrimental to the heart, vessels and kidneys, contributing to hypertension and the signs and progression of heart failure. Aldosterone secretion, abnormally elevated in heart failure and hypertension, can be blunted with angiotensin‐converting enzyme inhibitors. Amlodipine, used to treat hypertension and heart failure, was hypothesized to activate the renin‐angiotensin‐aldosterone system (RAAS). A study was conducted with six normal adult male beagle dogs. Each dog received amlodipine (0.57 mg/kg b.i.d.) for 6 days, followed by amlodipine (0.57 mg/kg b.i.d.) and enalapril (0.57 mg/kg b.i.d.) for 4 days. Blood pressure, heart rate, serum chemistries and urinary aldosterone excretion, as a measure of RAAS activation, were compared with baseline values. Blood pressure fell by approximately 7% with amlodipine (P = 0.05) and a further 7% with the combination of amlodipine and enalapril (P < 0.01). Blood urea nitrogen increased with the combination (P < 0.05) but only one dog became mildly azotemic. Renin‐angiotensin‐aldosterone system activation, based on 24 h urinary aldosterone excretion and by aldosterone:creatinine ratio was increased by approximately threefold (P < 0.05) with amlodipine administration. This effect was blunted by enalapril, such that aldosterone excretion was no longer different from that observed under control conditions, although values for 24‐h aldosterone excretion did not return to pretreament levels.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Atkins, C. E. and Rausch, W. P. and Gardner, S. Y. and Defrancesco, T. C. and Keene, B. W. and Levine, J. F.}, year={2007}, month={Oct}, pages={394–400} } @article{kelly_rolain_maggi_sontakke_keene_hunter_lepidi_breitschwerdt_breitschwerdt_raoult_et al._2006, title={Bartonella quintana Endocarditis in Dogs}, volume={12}, ISSN={1080-6040}, url={http://dx.doi.org/10.3201/eid1212.060724}, DOI={10.3201/eid1212.060724}, abstractNote={TOC summary line: PCR and sequencing provide the first evidence that B. quintana can be pathogenic in dogs.}, number={12}, journal={Emerging Infectious Diseases}, publisher={Centers for Disease Control and Prevention (CDC)}, author={Kelly, P. and Rolain, J. M. and Maggi, Ricardo and Sontakke, S. and Keene, B. and Hunter, S. and Lepidi, H. and Breitschwerdt, K. T. and Breitschwerdt, Edward and Raoult, D. and et al.}, year={2006}, pages={1869–1872} } @article{fujii_keene_mathews_atkins_defrancesco_hardie_wakao_2006, title={Coil occlusion of residual shunts after surgical closure of patent ductus arteriosus}, volume={35}, ISSN={["0161-3499"]}, DOI={10.1111/j.1532-950X.2006.00222.x}, abstractNote={Objective— To describe use of coil embolization to occlude residual flow through a patent ductus arteriosus (PDA) after incomplete surgical ligation.Study Design— Clinical study.Animals— Dogs (n=4) with continuous murmur after surgical ligation of PDA.Methods— After PDA ligation, residual ductal flow through the PDA was visible on color‐flow Doppler examination and left ventricular end‐diastolic diameter remained increased. Coil embolization by an arterial approach was performed to achieve complete occlusion of the PDA.Results— Embolization coils were delivered without complications and hemodynamically successful occlusion was achieved. Doppler‐visible flow resolved in 2 dogs within 3 months after embolization. Left ventricular end‐diastolic diameter indexed to body weight decreased in all dogs.Conclusions— Transcatheter coil embolization appears to be a safe and minimally invasive procedure for complete occlusion of residual PDA flow after incomplete surgical ligation.Clinical Relevance— Transcatheter coil embolization should be considered for correction of hemodynamically significant residual shunts in dogs that have incomplete PDA occlusion after open surgical ligation.}, number={8}, journal={VETERINARY SURGERY}, author={Fujii, Yoko and Keene, Bruce W. and Mathews, Kyle G. and Atkins, Clarke E. and Defrancesco, Teresa C. and Hardie, Elizabeth M. and Wakao, Yoshito}, year={2006}, month={Dec}, pages={781–785} } @article{kijtawornrat_nishijima_roche_keene_hamlin_2006, title={Use of a failing rabbit heart as a model to predict torsadogenicity}, volume={93}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfl025}, abstractNote={Humans with underlying cardiovascular disease are at greater risk than humans with normal hearts for developing torsade de pointes (TdP) following exposure to some drugs that prolong ventricular repolarization. This study was designed to test the hypothesis that rabbits with ischemic myocardial failure are at similarly increased risk of developing QTc prolongation and TdP following exposure to escalating doses of drugs, which is known to have a capacity to induce TdP in humans. Coronary artery ligation was performed in 28 rabbits, causing significant (p < 0.05) reduction in left ventricular shortening fraction and systolic myocardial dysfunction 4 weeks after ligation in all operated animals compared to 38 normal, nonoperated controls. All studies were performed on rabbits anesthetized with ketamine (35 mg/kg) and xylazine (5 mg/kg). Rabbits were exposed to escalating doses of amiodarone (3, 10, 30 mg/kg/10 min), cisapride (0.10, 0.25, 0.50 mg/kg/10 min), clofilium (0.1, 0.2, 0.4 mg/kg/10 min), dofetilide (0.005, 0.01, 0.02, 0.04 mg/kg/10 min), quinidine (3, 10, 30 mg/kg/10 min), and verapamil (0.25, 0.5, 1.0 mg/kg/10 min). A greater percentage of rabbits with failing hearts developed TdP following intravenous infusion of escalating doses of dofetilide (85%), clofilium (100%), or cisapride (50%) than did normal rabbits exposed to the same drug protocol (20, 33, and 0%, respectively). None of the rabbits in either group developed TdP when exposed to escalating doses of amiodarone, verapamil, or quinidine. Two out of four test articles lengthened QTc more in rabbits with myocardial failure than in normals, and TdP occurred in 13 out of 28 rabbits with myocardial failure as opposed to only four out of 38 rabbits with normal myocardial function.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Kijtawornrat, Anusak and Nishijima, Yoshinori and Roche, Brian M. and Keene, Bruce W. and Hamlin, Robert L.}, year={2006}, month={Sep}, pages={205–212} } @article{ozkanlar_kijtawornrat_hamlin_keene_roche_2005, title={Acute cardiovascular effects of tacrolimus in the isolated guinea pig heart}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00631.x}, abstractNote={Tacrolimus is an immunosuppressive, macrolide antibioticfrequently used to minimize transplant rejections. It has alsobeen used as a topical ointment to treat atopic dermatitis (Kappet al., 2003), and as an immunosuppressant in kidney trans-plants in dogs (Griffin et al., 1992). Macrolide antibiotics areknown to prolong ventricular repolarization, and to produce thepotentially fatal arrhythmia torsade de pointes (TdP).Reports by Johnson et al. (1992) and Hodak et al. (1998)describe TdP in patients receiving tacrolimus. TdP is a rapid,polymorphic, ventricular tachycardia produced most often bydrugs that lengthen the duration of depolarization and repolar-ization measured as the QT duration in the electrocardiogram(ECG). Tacrolimus has been shown to increase QTc (QT correctedfor heart rate) dispersion in patients with kidney transplants,implying a risk for TdP (Gerhart et al., 2001). A second study byGonza´lez et al. (1999) reported shortening of QTc in patientswith liver transplants treated with tacrolimus. The QTc disper-sion refers to the difference in durations of QTcs from numerousleads, and is thought to reflect heterogeneity of ventricularrepolarization, an electrophysiological substrate for early afterdepolarizations and re-entrant ventricular arrhythmias. Minem-atsu et al. (1999) demonstrated lengthening of QTc in a use-dependent manner showing counterclockwise hysteresis inanesthetized guinea pigs. Thus, the QTc lengthened more athigher heart rates than at lower heart rates – a pattern oppositeto that of most torsadogenic agents, which lengthen QTc in areverse-use dependent manner.There are two mechanisms by which tacrolimus may retardventricular repolarization. Tacrolimus blocks intermediate-con-ductance K}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Ozkanlar, Y and Kijtawornrat, A and Hamlin, RL and Keene, BW and Roche, BM}, year={2005}, month={Jun}, pages={313–316} } @article{kijtawornrat_ozkanlar_keene_roche_hamlin_hamlin_2006, title={Assessment of drug-induced QT interval prolongation in conscious rabbits}, volume={53}, ISSN={1056-8719}, url={http://dx.doi.org/10.1016/j.vascn.2005.04.013}, DOI={10.1016/j.vascn.2005.04.013}, abstractNote={Most preclinical trials are designed to identify potential torsadogenicity test only for surrogates of torsade de pointes, most commonly prolongation of the heart rate corrected QT interval (QTc). This study was conducted to determine which correction method best accounts for the effects of changes in the RR interval on the QT interval of conscious rabbits. This study was also conducted to validate the use of conscious, sling-trained rabbits to assess the QTc interval, and to evaluate the reliability and accuracy of this preparation in predicting drug-induced QTc prolongation in humans. ECGs were recorded via bipolar transthoracic ECG leads in 7 conscious rabbits previously trained to rest quietly in slings. The heart rate was slowed with 2.0 mg/kg zatebradine to assess the effects of heart rate on the QT interval. The same ECG and sling preparation was used to evaluate the effects in of three drugs known to be torsadogenic in humans (cisapride, dofetilide and haloperidol), two drugs known to be non-torsadogenic in humans (propranolol and enalaprilat) and a control article (vehicle). All of the test articles were administered intravenously to 4 rabbits, and both RR and QT intervals were measured and the corrected QT values were calculated by an investigator blinded to the test article, utilizing our own algorithm (QTc = QT / (RR)0.72) which permitted the least dependency of QTc on RR interval. The following regression equations were obtained relating QT to RR: QT = 2.4RR0.72, r2 = 0.79, with RR intervals varying between 210 and 350 ms. QTc lengthened significantly in all conscious rabbits given intravenous cisapride, dofetilide and haloperidol (p < 0.05), and QTc did not change with DMSO (vehicle control), propranolol or enalaprilat. Results indicate that a bipolar transthoracic ECG recorded in conscious, sling-trained rabbits may provide an easy and economical methodology useful in predicting QTc lengthening of novel pharmacological entities.}, number={2}, journal={Journal of Pharmacological and Toxicological Methods}, publisher={Elsevier BV}, author={Kijtawornrat, A. and Ozkanlar, Y. and Keene, B.W. and Roche, B.M. and Hamlin, D.M. and Hamlin, R.L.}, year={2006}, month={Mar}, pages={168–173} } @article{cesta_baty_keene_smoak_malarkey_2005, title={Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy}, volume={42}, ISSN={["1544-2217"]}, DOI={10.1354/vp.42-4-458}, abstractNote={ End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Cesta, MF and Baty, CJ and Keene, BW and Smoak, IW and Malarkey, DE}, year={2005}, month={Jul}, pages={458–467} } @article{hamlin_kijtawornrat_keene_2004, title={How many cardiac cycles must be measured to permit accurate RR, QT, and QTc estimates in conscious dogs?}, volume={50}, ISSN={1056-8719}, url={http://dx.doi.org/10.1016/j.vascn.2004.03.013}, DOI={10.1016/j.vascn.2004.03.013}, abstractNote={Electrocardiography is an essential tool to assess the liability of test articles to produce torsade de pointes. The number of cardiac cycles that must be measured from a dog to accurately characterize the relationship between RR and QT intervals, and thus assess this liability, is unknown.In this study, electrocardiograms (ECGs) were obtained from 12 conscious dogs with sinus rhythm. In each dog, RR and QT intervals were measured for 12 cardiac cycles. Measurements for each were then averaged over all 12 cycles, and those results compared to the average of both the initial 6 and 3 cycles, as well as to the middle cycle alone, for 12, 6, and 4 of the dogs. QTc was calculated by dividing each QT by the cube root of the preceding RR interval.We found no significant differences in the results of measurements of RR, QT, or QTc obtained from 12, 6, 3, or 1 cycle, whether from 12, 6, or 4 dogs. Intraobserver variability of ECG measurements was tested by having a single observer measure 10 copies of 12 different ECGs. The greatest coefficient of variation (S.D./mean) for the measurement of any ECG parameter was less than 2.5%.We conclude that measurements of RR and QT intervals made by a trained observer from 1 cardiac cycle accurately reflect those that are averaged from 3, 6, or 12 cycles whether the number of dogs per group is 12, 6, or 4.}, number={2}, journal={Journal of Pharmacological and Toxicological Methods}, publisher={Elsevier BV}, author={Hamlin, Robert L. and Kijtawornrat, Anusak and Keene, Bruce W.}, year={2004}, month={Sep}, pages={103–108} } @article{olby_harris_burr_munana_sharp_keene_2004, title={Recovery of pelvic limb function in dogs following acute intervertebral disc herniations}, volume={21}, ISSN={["1557-9042"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0942290535&partnerID=MN8TOARS}, DOI={10.1089/089771504772695940}, abstractNote={Chondrodystrophoid breeds of dog are prone to explosive herniation of mineralized disc material into the thoracolumbar spinal canal. The resulting acute spinal cord injury may represent an excellent spontaneous model of acute traumatic spinal cord injury. The aims of this study were to quantify the recovery of dogs following acute disc herniations, to evaluate external factors that influence recovery, and to identify a group of dogs suitable for use in clinical trials on neuroprotective drugs. The gait of 88 dogs with thoracolumbar disc herniations was scored at the time of injury and 2, 4, and 12 weeks after surgical decompression. Dogs were placed into four groups dependent on the severity of presenting signs; dogs in group 1 had the most severe injury severity. Group 1 dogs showed a variable but incomplete recovery by 12 weeks. Dogs in groups 2 and 3 recovered uniformly but more completely, while dogs in group 4 made a rapid and excellent recovery and were deemed unsuitable for clinical trials. Combining dogs in groups 1, 2 and 3 produced a population of dogs with incomplete recovery by 12 weeks. Power analysis revealed that 87 such dogs would be needed per treatment group to detect a 20% change in function with a power of 95%. The number needed reduced drastically to 19 by eliminating dogs in group 1, but this produced less room for functional improvement. External factors did not appear to influence outcome. We conclude that dogs with spontaneous disc herniations provide a useful model of acute spinal cord injury for clinical trials.}, number={1}, journal={JOURNAL OF NEUROTRAUMA}, author={Olby, N and Harris, T and Burr, J and Munana, K and Sharp, N and Keene, B}, year={2004}, month={Jan}, pages={49–59} } @article{glaus_hassig_keene_2003, title={Accuracy of heart rate obtained by auscultation in atrial fibrillation}, volume={39}, ISSN={["0587-2871"]}, DOI={10.5326/0390237}, abstractNote={The accuracy of heart rate estimation by cardiac auscultation over a 15-second period, and the influence of clinical experience on accuracy were evaluated in a dog with chronic atrial fibrillation by test subjects of varying experience. Only 30% of all test subjects provided accurate heart rate estimates. Board-certified specialists, medicine residents, and experienced nurses were significantly more accurate in their estimates than surgery residents and students. Accurate estimates were provided by 12.5% of surgery residents and students, as opposed to 64% of the other test subjects. Auscultatory estimates of heart rate in atrial fibrillation may be significantly inaccurate, and under some circumstances they may not provide a sound basis for making clinical decisions.}, number={3}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Glaus, TM and Hassig, M and Keene, BW}, year={2003}, pages={237–239} } @article{defrancesco_hansen_atkins_sidley_keene_2003, title={Noninvasive transthoracic temporary cardiac pacing in dogs}, volume={17}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2003)017<0663:NTTCPI>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 17, Issue 5 p. 663-667 Open Access Noninvasive Transthoracic Temporary Cardiac Pacing in Dogs Teresa C. DeFrancesco, Corresponding Author Teresa C. DeFrancesco Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC. College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected].Search for more papers by this authorBernard D. Hansen, Bernard D. Hansen Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorClarke E. Atkins, Clarke E. Atkins Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorJennifer A. Sidley, Jennifer A. Sidley Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorBruce W. Keene, Bruce W. Keene Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this author Teresa C. DeFrancesco, Corresponding Author Teresa C. DeFrancesco Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC. College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected].Search for more papers by this authorBernard D. Hansen, Bernard D. Hansen Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorClarke E. Atkins, Clarke E. Atkins Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorJennifer A. Sidley, Jennifer A. Sidley Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorBruce W. Keene, Bruce W. Keene Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2003.tb02497.xCitations: 33AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Temporary cardiac pacing is used in the emergency treatment of life-threatening bradyarrhythmias and for the support of heart rate and blood pressure of patients with sick sinus syndrome or high-grade atrioventricular (AV) block undergoing general anesthesia, typically for permanent pacemaker implantation. We retrospectively evaluated the safety and efficacy of a noninvasive transthoracic external cardiac pacing system in 42 dogs treated for bradyarrhythmias. Optimal placement of the patch electrodes on the skin of the thorax was initially established on 2 anesthetized normal dogs. The optimal electrode placement was determined to be on the right and left hemithoraces, directly over the heart. Afterward, by means of this electrode placement, all 42 dogs treated for bradyarrhythmias in this study were successfully paced with the noninvasive transthoracic system. Dogs ranged in age from 1 to 15 years and weighed between 3.2 and 40 kg. Miniature Schnauzers, German Shepherds, and mixed breeds were most common in the study population. Indications for noninvasive transthoracic pacing included emergency treatment of hemodynamically unstable 3rd-degree AV block (2 dogs); support of heart rate during general anesthesia for permanent pacemaker implantation or lead-wire adjustment (38 dogs); and support of heart rate during general anesthesia for ophthalmologic surgery in dogs with sick sinus syndrome (2 dogs). Complications included pain and skeletal muscle stimulation, which required general anesthesia. We conclude that the noninvasive transthoracic pacing system evaluated is satisfactory for clinical veterinary use. References 1 Yoshioka MM, Tilley LP, Harvey HJ, et al. Permanent pacemaker implantation in the dog. J Am Anim Hosp Assoc 1981; 17: 746–750. 2 Bonagura JD, Helphrey ML, Muir WW. Complications associated with permanent pacemaker implantation in the dog. J Am Vet Med Assoc 1983; 182: 149–155. 3 Klement P., Del-Nido PJ, Wilson GJ. The use of cardiac pacemakers in veterinary practice. Compendium 1984; 6: 893–902. 4 Fox PR, Matthiesen DT, Purse D., et al. Ventral abdominal, trans-diaphragmatic approach for implantation of cardiac pacemakers in the dog. J Am Vet Med Assoc 1986; 189: 1303–1308. 5 Sisson D., Thomas WP, Woodfield J., et al. Permanent transvenous pacemaker implantation in forty dogs. J Vet Intern Med 1991; 5: 322–331. 6 Flanders JA, Moise NS, Gelzer ARM, et al. Introduction of an endocardial pacing lead through the costocervical vein in six dogs. J Am Vet Med Assoc 1999; 215: 46–48. 7 Cote E., Laste NJ. Transvenous cardiac pacing. Clin Tech Small Anim Pract 2000; 15: 165–176. 8 Hynes JK, Holmes DR, Harrison CE. Five-year experience with temporary pacemaker therapy in the coronary care unit. Mayo Clin Proc 1983; 58: 122–126. 9 Hildick-Smith DJR, Petch MC. Temporary pacing before per-manent pacing should be avoided unless essential. Br Med J 1999; 317: 79–80. 10 Murphy JJ. Problems with temporary cardiac pacing. Br Med J 2001; 323: 527. 11 Zoll PM. Resuscitation of the heart in ventricular standstill by external electric stimulation. N Engl J Med 1952; 13: 768–771. 12 Zoll PM, Zoll RH, Belgard AH. External noninvasive electric stimulation of the heart. Crit Care Med 1981; 9: 393–394. 13 Falk RH, Zoll PM, Zoll RH. Safety and efficacy of noninvasive cardiac pacing. N Engl J Med 1983; 309: 1166–1168. 14 Zoll PM, Zoll RH, Falk RH, et al. External noninvasive temporary cardiac pacing: Clinical trials. Circulation 1985; 71: 937–944. 15 White JD, Brown CG. Immediate transthoracic pacing for cardiac asystole in an emergency department setting. Am J Emerg Med 1985; 3: 125–128. 16 Allen PW, OToole JJ. External transthoracic pacemaking. Anaesthesia 1988; 43: 895–896. 17 Madsen JK, Meibom J., Videbak R., et al. Transcutaneous pacing: Experience with the Zoll noninvasive temporary pacemaker. Am Heart J 1988; 116: 7–10. 18 Normal myocardial enzymes and normal echocardiographic findings during noninvasive transcutaneous pacing Pacing Clin Elec-trophysiol 1988; 11: 1188–1193. 19 Kirschenbaum LP, Eisenkraft JB, Mitchell J., Hillel Z. Transtho-racic pacing for the treatment of severe bradycardia during induction of anesthesia. J Cardiothorac Anesth 1989; 3: 329–332. 20 Wood M., Ellenbogen KA. Bradyarrhythmias, emergency pacing and implantable defibrillation devices. Crit Care Clin 1989; 5: 551–568. 21 Hedges JR, Feero S., Shultz B., et al. Prehospital transcutaneous cardiac pacing for symptomatic bradycardia. Pacing Clin Electrophy-siol 1991; 14: 1473–1478. 22 Gammage MD. Temporary cardiac pacing. Heart 2000; 83: 715–720. 23 Syverud SA, Dalsey WC, Hedges JR, et al. Transcutaneous cardiac pacing: Determination of myocardial injury in the canine model. Ann Emerg Med 1983; 12: 745–748. 24 Kicklighter EJ, Syverud SA, Dalsey WC, et al. Pathological aspects of transcutaneous cardiac pacing. Am J Emerg Med 1985; 3: 108–113. 25 Syverud SA, Hedges JR, Dalsey WC, et al. Hemodynamics of transcutaneous cardiac pacing. Am J Emerg Med 1986; 4: 17–20. 26 Niemann JT, Rosborough JP, Garner D., et al. External nonin-vasive cardiac pacing; comparative hemodynamic study of two techniques with conventional endocardial pacing. Pacing Clin Electrophy-siol 1988; 11: 575–582. 27 Hedges JR, Syverud SA, Dalsey WC, et al. Threshold, enzymatic, and pathologic changes associated with prolonged transcuta-neous pacing in a chronic heart block model. J Emerg Med 1989; 7: 1–4. 28 Oyama MA, Sisson DD, Lehmkuhl LB. Practices and outcomes of artificial cardiac pacing in 154 dogs. J Vet Intern Med 2001; 15: 229–239. Citing Literature Volume17, Issue5September 2003Pages 663-667 ReferencesRelatedInformation}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={DeFrancesco, TC and Hansen, BD and Atkins, CE and Sidley, JA and Keene, BW}, year={2003}, pages={663–667} } @article{hamlin_kijtawornrat_keene_hamlin_2003, title={QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles}, volume={76}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfg254}, abstractNote={A facile system for obtaining electrocardiograms from conscious animals was used to conduct studies on 12 animals studied both conscious and anesthetized, on 4 conscious animals given vehicle (0.5% methylcellulose) and QT-lengthening test articles, and on 6 animals given test articles thought to not lengthen QTc. In 12 animals whose ECGs were monitored via a bipolar transthoracic ECG, heart rates were slowed with 1.0 mg/kg zatebradine, while they were conscious in their slings, and after being anesthetized with ketamine/xylazine. The following regression equations were obtained relating QT to RR: QT = 44.7 ln RR - 132.9, r2 = 0.7, for conscious animals; QT = 79.4 ln RR - 287.4, r2 = 0.8 for anesthetized animals, with RR intervals varying between 150 and 550 ms. The anesthetic increases QT at all RR intervals (p < 0.001), but does not change the slope of the relationship between QT and RR when compared with the conscious guinea pig. The Fridericia method was best for correcting QT for RR interval in conscious guinea pigs, but the Bazett method was best for correcting in anesthetized animals. QTc lengthened significantly in all conscious guinea pigs given, orally, cisapride, ketoconazole, and sotalol (positive test articles) and did not change with methylcellulose (the vehicle) or with propranolol, verapamil, or enalapril (negative controls). These techniques and relationships demonstrate that this methodology may be useful in exploring torsadogenic effects of novel pharmacological entities.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Hamlin, RL and Kijtawornrat, A and Keene, BW and Hamlin, DM}, year={2003}, month={Dec}, pages={437–442} } @article{hamlin_cruze_mittelstadt_kijtawornrat_keene_roche_nakayama_nakayama_hamlin_arnold_2004, title={Sensitivity and specificity of isolated perfused guinea pig heart to test for drug-induced lengthening of QTc}, volume={49}, ISSN={1056-8719}, url={http://dx.doi.org/10.1016/j.vascn.2003.08.003}, DOI={10.1016/j.vascn.2003.08.003}, abstractNote={Introduction: The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). Methods: QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts were exposed to escalating concentrations of 26 compounds thought to lengthen, and 13 compounds thought not to lengthen, QTc in humans. Results: In this preparation, QTc was found to lengthen in 26 of 26 compounds thought to be positive (sensitivity 1.00) and not to lengthen or to lengthen insignificantly in 13 of 13 compounds thought to be negative (specificity 1.0) in man. Probucol and ontazolast could not be studied because of limited solubility. Successful experiments were conducted on over 98% of guinea pigs anesthetized. Discussion: We believe that the isolated perfused guinea pig heart is an in vitro preparation that could be utilized early in preclinical testing for identifying a liability to lengthen QTc in humans, but we do not believe—as is true also for other in vitro methods—that the concentration at which the liability is demonstrated in vitro necessarily predicts the concentration at which a liability exists in man.}, number={1}, journal={Journal of Pharmacological and Toxicological Methods}, publisher={Elsevier BV}, author={Hamlin, R.L and Cruze, C.A and Mittelstadt, S.W and Kijtawornrat, A and Keene, B.W and Roche, B.M and Nakayama, T and Nakayama, H and Hamlin, D.M and Arnold, T}, year={2004}, month={Jan}, pages={15–23} } @article{rausch_keene_2003, title={Spontaneous resolution of an isolated ventricular septal defect in a dog}, volume={223}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2003.223.219}, abstractNote={A 5-month-old Maltese was examined because of a holosystolic heart murmur. Results of echocardiography were suggestive of a small isolated interventricular septal defect. Color flow and pulsed-wave spectral Doppler echocardiography confirmed that there was left-to-right blood flow through the defect during systole and diastole. Because of the small size of the defect, the large systolic pressure differential between the ventricles (72.6 mm Hg), and the lack of clinical signs, the small amount of left-to-right shunting was considered clinically unimportant, and no medication or treatment was recommended. Seven months later, the dog was re-examined, and trans-septal blood flow was no longer seen. Isolated interventricular septal defects are a common congenital heart disorder in some breeds of dogs. Such defects may be subclinical in some dogs. In others, they cause a wide spectrum of clinical problems. Findings in this dog suggest that interventricular septal defects may close spontaneously in some dogs.}, number={2}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Rausch, WP and Keene, BW}, year={2003}, month={Jul}, pages={219–220} } @article{meurs_spier_wright_atkins_defrancesco_gordon_hamlin_keene_miller_moise_et al._2002, title={Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxers}, volume={221}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2002.221.522}, DOI={10.2460/javma.2002.221.522}, abstractNote={Abstract Objective—To evaluate the effect of 4 antiarrhythmic treatment protocols on number of ventricular premature complexes (VPC), severity of arrhythmia, heart rate (HR), and number of syncopal episodes in Boxers with ventricular tachyarrhythmias. Design—Randomized controlled clinical trial. Animals—49 Boxers. Procedure—Dogs with > 500 VPC/24 h via 24-hour ambulatory ECG (AECG) were treated with atenolol (n = 11), procainamide (11), sotalol (16), or mexiletine and atenolol (11) for 21 to 28 days. Results of pre- and posttreatment AECG were compared with regard to number of VPC/24 h; maximum, mean, and minimum HR; severity of arrhythmia; and occurrence of syncope. Results—Significant differences between pre- and posttreatment number of VPC, severity of arrhythmia, HR variables, or occurrence of syncope were not observed in dogs treated with atenolol or procainamide. Significant reductions in number of VPC, severity of arrythmia, and maximum and mean HR were observed in dogs treated with mexiletineatenolol or sotalol; occurrence of syncope was not significantly different between these 2 treatment groups. Conclusions and Clinical Relevance—Treatment with sotalol or mexiletine-atenolol was well tolerated and efficacious. Treatment with procainamide or atenolol was not effective. (J Am Vet Med Assoc 2002;221:522–527)}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, K. M. and Spier, A. W. and Wright, N. A. and Atkins, C. E. and DeFrancesco, Teresa and Gordon, S. G. and Hamlin, R. L. and Keene, B. W. and Miller, M. W. and Moise, N. S. and et al.}, year={2002}, month={Aug}, pages={522–527} } @article{atkins_brown_coats_crawford_defrancesco_edwards_fox_keene_lehmkuhl_luethy_et al._2002, title={Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation}, volume={221}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2002.221.654}, DOI={10.2460/javma.2002.221.654}, abstractNote={AbstractObjective—To determine the effect of long-term administration of enalapril on renal function in dogs with severe, compensated mitral regurgitation.Design—Randomized controlled trial.Animals—139 dogs with mitral regurgitation but without overt signs of heart failure.Procedure—Dogs were randomly assigned to be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and serum creatinine and urea nitrogen concentrations were measured at regular intervals for up to 26 months.Results—Adequate information on renal function was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median, 12 months). Mean serum creatinine and urea nitrogen concentrations were not significantly different between dogs receiving enalapril and dogs receiving the placebo at any time, nor were concentrations significantly different from baseline concentrations. Proportions of dogs that developed azotemia or that had a ≥ 35% increase in serum creatinine or urea nitrogen concentration were also not significantly different between groups.Conclusions and Clinical Relevance—Results suggest that administration of enalapril for up to 2 years did not have any demonstrable adverse effects on renal function in dogs with severe, compensated mitral regurgitation. (J Am Vet Med Assoc2002;221: 654–658)}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Atkins, Clarke E. and Brown, William A. and Coats, Julie R. and Crawford, Mary Ann and DeFrancesco, Teresa C. and Edwards, Joel and Fox, Philip R. and Keene, Bruce W. and Lehmkuhl, Linda and Luethy, Michael and et al.}, year={2002}, month={Sep}, pages={654–658} } @article{pressler_rotstein_law_rosol_leroy_keene_jackson_2002, title={Hypercalcemia and high parathyroid hormone-related protein concentration associated with malignant melanoma in a dog}, volume={221}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2002.221.263}, abstractNote={A 12-year-old Cocker Spaniel with an oral malignant melanoma was evaluated for progressive lethargy and anorexia. No metastases were identified during antemortem evaluation, but severe hypercalcemia was evident. Antemortem diagnostic testing failed to identify a cause for the hypercalcemia. No neoplasms other than the melanoma were identified on postmortem examination. Serum parathyroid hormone-related protein concentration was markedly high, and the melanoma had moderate to marked immunostaining for this protein. Paraneoplastic syndromes are rare in dogs with malignant melanoma.}, number={2}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Pressler, BM and Rotstein, DS and Law, JM and Rosol, TJ and LeRoy, B and Keene, BW and Jackson, MW}, year={2002}, month={Jul}, pages={263-+} } @article{sidley_atkins_keene_defrancesco_2002, title={Percutaneous Balloon Pericardiotomy as a Treatment for Recurrent Pericardial Effusion in 6 Dogs}, volume={16}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2002.tb02384.x}, DOI={10.1892/0891-6640(2002)016<0541:PBPAAT>2.3.CO;2}, abstractNote={Percutaneous balloon pericardiotomy (PBP) has been performed in people and in a small number of dogs as a treatment for recurrent pericardial effusion with tamponade (PET). We performed this technique on 6 dogs with recurrent PET (5 with heart base tumors and 1 with no identifiable mass). Under general anesthesia and fluoroscopic guidance, a balloon-dilating catheter (diameters 14-20 mm) was introduced percutaneously at the 5th intercostal space through a sheath-introducing catheter, positioned across the parietal pericardium, and inflated 3 times. No dog experienced serious complications. The procedure was considered successful in 4 of 6 dogs. One dog is still alive without recurrence of PET 1 year after the procedure. Three dogs died of unrelated disease without recurrence of PET 5. 19, and 32 months after the procedure. The procedure was not beneficial in 1 dog that was euthanized 9 weeks later because of recurrence of pleural and abdominal effusion thought to be secondary to PET. One dog may have temporarily benefited but developed symptomatic PET 6 months after PBP. PBP appears to be a safe, economical, and potentially effective palliative treatment for recurrent PET and is a reasonable, less invasive alternative to surgery for dogs with recurrent PET, especially effusions caused by heart base tumors and possibly idiopathic pericardial effusion. Premature closure of the stoma is a potential cause for long-term failure and was thought to have been responsible for the recurrence of clinical signs in 2 dogs.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Sidley, J.A. and Atkins, C.E. and Keene, B.W. and DeFrancesco, T.C.}, year={2002}, month={Sep}, pages={541–546} } @article{little_keene_bruton_smith_powell_jones_2002, title={Percutaneous retrieval of a jugular catheter fragment from the pulmonary artery of a foal}, volume={220}, ISSN={["0003-1488"]}, url={http://europepmc.org/abstract/med/12126133}, DOI={10.2460/javma.2002.220.212}, abstractNote={A 49-kg (107.8-lb) sexually intact male Arabian foal was evaluated at 3 days of age because of profuse watery diarrhea, anorexia, and signs of abdominal pain. Physical examination findings were unremarkable except for evidence of diarrhea. A catheter was placed in the right jugular vein for administration of antimicrobials and lactated Ringer's solution. The foal was discharged with instructions to the owner to continue antimicrobial administration and fluid therapy; at home, the owner inadvertently cut the catheter at the level of the hub during attempted removal, and the catheter fragment migrated distally in the jugular vein and subsequently lodged in the pulmonary artery. The foal was readmitted to the hospital for retrieval of the fragment, using a percutaneous retrieval technique. Catheter fragmentation is a well-recognized risk of catheterization in horses. Catheter fragments can be retrieved somewhat easily from the jugular vein; however, if the fragment migrates to the heart or pulmonary artery, imaging the fragment to locate and retrieve it can be difficult. Complications associated with catheter fragmentation include septicemia, endocarditis, lung abscesses, pulmonary embolism, dysrhythmias, cardiac perforation, pulmonary or caval thrombosis, and death. To our knowledge, this is the first report of successful retrieval of a catheter fragment from the pulmonary artery in a horse.}, number={2}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Little, D and Keene, BW and Bruton, C and Smith, LJ and Powell, S and Jones, SL}, year={2002}, month={Jan}, pages={212–214} } @article{defrancesco_atkins_keene_coats_hauck_2002, title={Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0553:PCEOSC>2.3.CO;2}, abstractNote={The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1,5,7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={DeFrancesco, TC and Atkins, CE and Keene, BW and Coats, JR and Hauck, ML}, year={2002}, pages={553–557} } @article{olby_de risio_munana_wosar_skeen_sharp_keene_2001, title={Development of a functional scoring system in dogs with acute spinal cord injuries}, volume={62}, ISSN={["1943-5681"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035487722&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2001.62.1624}, abstractNote={AbstractObjective—To develop and compare the reliability of 2 methods of scoring pelvic limb gait in dogs recovering from thoracolumbar spinal cord injuries and to use this scoring system to determine the rate and level of functional recovery of dogs with acute thoracolumbar intervertebral disk herniations.Animals—46 dogs with spinal cord injuries resulting from intervertebral disk herniations.Procedure—Dogs' gaits were videotaped at different time intervals after injury. In phase 1 of the study, the stages of recovery of pelvic limb function were identified, and a numeric scoring system was devised to reflect that recovery. In phase 2, pelvic limb gait was scored by different observers, using a numeric and a visual analog scale. Intra- and interobserver coefficients of variability of both methods were compared. In phase 3, pelvic limb function was scored, using the numeric scale at various intervals after acute thoracolumbar disk herniations.Results—The numeric scale was significantly more reliable than the visual analog scale when both intraand interobserver coefficients of variability were evaluated. Dogs that were paraplegic with no deep pain sensation recovered at different rates during the first 3 months, whereas dogs that were paraplegic with deep pain sensation typically recovered within 1 month of injury.Conclusion and Clinical Relevance—Pelvic limb gait of dogs recovering from thoracolumbar spinal cord injuries can be reliably quantified, using a numeric scale. This scale will facilitate the performance of clinical trials aimed at improving the outcome of acute spinal cord injuries. (Am J Vet Res2001;62:1624–1628)}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Olby, NJ and De Risio, L and Munana, KR and Wosar, MA and Skeen, TM and Sharp, NJH and Keene, BW}, year={2001}, month={Oct}, pages={1624–1628} } @article{mc entee_flandre_dessy_desmecht_clercx_balligand_michaux_jonville_miserque_henroteaux_et al._2001, title={Metabolic and structural abnormalities in dogs with early left ventricular dysfunction induced by incessant tachycardia}, volume={62}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2001.62.889}, abstractNote={AbstractObjective—To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP).Animals—7 Beagles.Procedure—Plasma carnitine concentrations were measured before and after development of ELVD induced by RRVP. At the same times, transvenous endomyocardial biopsy was performed, and specimens were submitted for determination of myocardial carnitine concentrations and histologic, morphometric, and ultrastructural examination.Results—In 4 dogs in which baseline plasma total carnitine concentration was normal, RRVP induced a decrease in myocardial total and free carnitine concentrations and an increase in myocardial esterified carnitine concentration. In 3 dogs in which baseline plasma total carnitine concentration was low, plasma and myocardial carnitine concentrations were unchanged after pacing. Structural changes associated with pacing included perinuclear vacuolization in 3 dogs. Morphometric analyses indicated there was a decrease in myofiber cross-sectional diameter and area following pacing. Electron microscopy revealed changes in myofibrils and mitochondria following pacing.Conclusions and Clinical Relevance—Results indicated that moderate to severe alterations in myocyte cytoarchitecture are present in dogs with ELVD induced by RRVP and that in dogs with normal plasma carnitine concentrations, myocardial carnitine deficiency may be a biochemical marker of ELVD. Results also indicated that transvenous endomyocardial biopsy can be used to evaluate biochemical and structural myocardial changes in dogs with cardiac disease. (Am J Vet Res2001;62:889–894)}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Mc Entee, K and Flandre, T and Dessy, C and Desmecht, D and Clercx, C and Balligand, M and Michaux, C and Jonville, E and Miserque, N and Henroteaux, M and et al.}, year={2001}, month={Jun}, pages={889–894} } @article{baty_malarkey_atkins_defrancesco_sidley_keene_2001, title={Natural history of hypertrophic cardiomyopathy and aortic thromboembolism in a family of domestic shorthair cats}, volume={15}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2001)015<0595:NHOHCA>2.3.CO;2}, abstractNote={A feline domestic shorthair queen and her 3 offspring were all diagnosed with asymptomatic hypertrophic cardiomyopathy (HCM). The family has been followed for 13 years, and 3 cats have died of aortic thromboembolism (ATE). This communication documents the long-term progression of HCM in these cats that presented with mild left ventricular hypertrophy and hyperdynamic systolic ventricular function, developed progressive left atrial enlargement, and eventually resulted in hypodynamic left ventricular systolic function with relative left ventricular chamber dilation at the time of ATE.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Baty, CJ and Malarkey, DE and Atkins, CE and DeFrancesco, TC and Sidley, J and Keene, BW}, year={2001}, pages={595–599} } @article{defrancesco_atkins_miller_meurs_keene_2001, title={Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985-1997)}, volume={218}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2001.218.66}, DOI={10.2460/javma.2001.218.66}, abstractNote={AbstractObjective—To determine the usefulness of echocardiography in the diagnosis of heartworm disease in cats and to compare this modality with other tests.Design—Retrospective study.Animals—43 cats with heartworm infection that had echocardiographic examinations at 2 veterinary teaching hospitals between 1985 and 1997. Twenty-two of these 43 cats also underwent radiography of the thorax and heartworm antibody and heartworm antigen testing.Procedure—Cats were determined to be infected withDirofilaria immitisinfection on the basis of 1 or more of the following findings: positive modified Knott or antigen test result, echocardiographic evidence of heartworm disease, or confirmation of the disease on postmortem examination. The percentage of echocardiographs in which heartworms were evident was compared with the percentage of radiographs in which pulmonary artery enlargement was evident and results of antigen or antibody tests in cats in which all tests were performed.Results—Overall, heartworms were detectable by use of echocardiography in 17 of 43 cats, most often in the pulmonary arteries. In the 22 cats in which all tests were performed, antibody test results were positive in 18, antigen test results were positive in 12, and pulmonary artery enlargement was evident radiographically and heartworms were identifiable echocardiographically in 14. Heartworm infection was diagnosed exclusively by use of echocardiography in 5 cats in which the antigen test result was negative.Conclusions and Clinical Relevance—Although echocardiography was less sensitive than antigen testing, it was a useful adjunctive test in cats that had negative antigen test results in which there was a suspicion of heartworm disease. The pulmonary arteries should be evaluated carefully to increase the likelihood of detection of heartworms echocardiographically. ( J Am Vet Med Assoc2001;218:66–69)}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={DeFrancesco, Teresa C. and Atkins, Clarke E. and Miller, Matthew W. and Meurs, Kathryn M. and Keene, Bruce W.}, year={2001}, month={Jan}, pages={66–69} } @article{atkins_defrancesco_coats_sidley_keene_2000, title={Heartworm infection in cats: 50 cases (1985-1997)}, volume={217}, DOI={10.2460/javma.2000.217.355}, abstractNote={AbstractObjective—To characterize risk factors, clinical findings, usefulness of diagnostic tests, and prognosis in cats with naturally occurring heartworm infection (HWI).Design—Retrospective study.Animals—50 cats withDirofilaria immitisinfection.Procedure—Medical records, thoracic radiographs, and echocardiograms were reviewed and findings compared with appropriate reference populations.Results—Findings suggested that male cats were not predisposed to HWI, domestic shorthair cats were at increased risk, and indoor housing was only partially protective. Fewer cases of HWI were identified in the final quarter of the year, compared with other periods, and prevalence is not apparently increasing. Signs of respiratory tract disease were most common, followed by vomiting. Infection was diagnosed incidentally in > 25% of cats; conversely, 10% of infected cats died suddenly without other clinical signs. Serologic tests were most useful for diagnosis, followed by radiography and echocardiography. Eosinophilia supported the diagnosis. Overall median survival time was 1.5 years but exceeded 4 years in cats surviving beyond the day of diagnosis.Conclusions and Clinical Relevance—Sex does not appear to be a risk factor for HWI in cats, and indoor housing provides only incomplete protection. Signs of respiratory tract disease (dyspnea and cough) are the strongest indicators of HWI in cats, and some radiographic evidence of infection is detected in most cases. Antibody screening for HWI in cats is efficacious, and antigen testing and echocardiography are most useful for making a definitive antemortem diagnosis. (J Am Vet Med Assoc2000;217: 355–358)}, number={3}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Atkins, CE and DeFrancesco, TC and Coats, JR and Sidley, JA and Keene, BW}, year={2000}, month={Aug}, pages={355–358} } @article{keene_2000, title={Towards evidence-based veterinary medicine}, volume={14}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.2000.tb02223.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 14, Issue 2 p. 118-119 Open Access Editorial: Towards Evidence-Based Veterinary Medicine Bruce W. Keene DVM, MSc, Bruce W. Keene DVM, MSc Diplomate, ACVIM, Cardiology Associate Professor of Cardiology Director, NCSU Veterinary Clinical Trials Program College of Veterinary Medicine North Carolina State University 4700 Hillsborough Street Raleigh, NC 27606 e-mail: Bruce_Keene@ncsu.eduSearch for more papers by this author Bruce W. Keene DVM, MSc, Bruce W. Keene DVM, MSc Diplomate, ACVIM, Cardiology Associate Professor of Cardiology Director, NCSU Veterinary Clinical Trials Program College of Veterinary Medicine North Carolina State University 4700 Hillsborough Street Raleigh, NC 27606 e-mail: Bruce_Keene@ncsu.eduSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2000.tb02223.xCitations: 29AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume14, Issue2March 2000Pages 118-119 ReferencesRelatedInformation}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Keene, BW}, year={2000}, pages={118–119} } @article{schatzberg_olby_steingold_keene_atkins_meurs_solomon_goedegebuure_wilton_sharp_1999, title={A polymerase chain reaction screening strategy for the promoter of the canine dystrophin gene}, volume={60}, number={9}, journal={American Journal of Veterinary Research}, author={Schatzberg, S. and Olby, N. and Steingold, S. and Keene, B. and Atkins, C. and Meurs, K. and Solomon, G. and Goedegebuure, S. A. and Wilton, S. and Sharp, N.}, year={1999}, pages={1040–1046} } @article{alexander_keene_yount_geratz_small_baric_1999, title={ECG changes after rabbit coronavirus infection}, volume={32}, ISSN={["0022-0736"]}, DOI={10.1016/S0022-0736(99)90018-3}, abstractNote={This study examines the electrocardiographic (ECG) changes following rabbit coronavirus (RbCV) infection. We have shown that infection with RbCV results in the development of myocarditis and congestive heart failure and that some survivors of RbCV infection go on to develop dilated cardiomyopathy in the chronic phase. Serial ECGs were recorded on 31 RbCV-infected rabbits. Measurements of heart rate; P-R interval; QRS duration; QTc interval; and P-, QRS-, and T-wave voltages were taken. The recordings were also examined for disturbances of conduction, rhythm, and repolarization. The acute and subacute phases were characterized by sinus tachycardia with depressed R- and T-wave voltages as well as disturbances of conduction, rhythm, and repolarization. In most animals in the chronic phase, the sinus rate returned to near-baseline values with resolution of the QRS voltage changes. The ECG changes observed during RbCV infection are similar to the spectrum of interval/segment abnormalities, rhythm disturbances, conduction defects, and myocardial pathology seen in human myocarditis, heart failure, and dilated cardiomyopathy. Because animals often died suddenly in the absence of severe clinical signs of congestive heart failure during the acute phase, RbCV infection may increase ventricular vulnerability, resulting in sudden cardiac death. RbCV infection may provide a rare opportunity to study sudden cardiac death in an animal model in which the ventricle is capable of supporting ventricular fibrillation, and invasive techniques monitoring cardiac function can be performed.}, number={1}, journal={JOURNAL OF ELECTROCARDIOLOGY}, author={Alexander, LK and Keene, BW and Yount, BL and Geratz, JD and Small, JD and Baric, RS}, year={1999}, month={Jan}, pages={21–32} } @article{atkins_defrancesco_miller_meurs_keene_1998, title={Prevalence of heartworm infection in cats with signs of cardiorespiratory abnormalities}, volume={212}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Atkins, C. E. and DeFrancesco, T. C. and Miller, M. W. and Meurs, K. M. and Keene, B.}, year={1998}, pages={517–520} } @article{carroll_keene_forrest_1997, title={Asystole associated with iohexol myelography in a dog}, volume={38}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1997.tb00857.x}, abstractNote={This is areport of a 10‐year‐old female neutered Doberman Pinscher with a clinical diagnosis of myelopathy. The dog was anesthetized using oxymorphone, thiopental, and halothane in oxygen for a cerebrospinal tap and a myelogram. Iohexsal injection into the subarachnoid space by lumbar puncture was uneventful. Additional iohexal was given into the cerebellomjedullary cistern. Immediately following iohexal administration into the cerebellomedullary cistern, several electrocardiographic changes occurred. Two extended periods of asystole responded to intravenous glycopyrrolate administration. A slow multiform ventricular escape rhythm was established after the second dose of glycopyrrolate. Ultimately, atrial activity with apparent A V dissociation resumed, atrial fibrillation developed, and the rhythm converted to normal sinus rhythm. The dog had a normal cardiac examination the following day. Two days later, the dog was anesthetized using a similar anesthetic regimen with maintance on isoflurane in oxygen for a hemilaminectomy. The dog recovered uneventfully from surgery and was discharged 2 days later.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Carroll, GL and Keene, BW and Forrest, LJ}, year={1997}, pages={284–287} } @article{kittleson_keene_pion_loyer_beardow_knight_bonagura_burgener_delellis_goullaud_et al._1997, title={Results of the Multicenter Spaniel Trial (MUST): Taurine- and carnitine-responsive dilated cardiomyopathy in American cocker spaniels with decreased plasma taurine concentration}, volume={11}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.1997.tb00092.x}, abstractNote={Fourteen American Cocker Spaniels (ACS) with dilated cardiomyopathy (DCM) were studied to determine if individuals of this breed with DCM are systemically taurine‐or carnitine‐deficient and to determine if they are responsive to taurine and carnitine supplementation. American Cocker Spaniels with DCM were identified using echocardiography, and plasma was analyzed for taurine and carnitine concentrations. Each dog was randomly assigned to receive either taurine and carnitine supplementation or placebos. Echocardiograms and clinical examinations were repeated monthly for 4 months. During this period, the investigators and owners were blinded with respect to the treatment being administered. Each dog was weaned off its cardiovascular drugs (furosemide, digoxin, and an angiotensin converting enzyme inhibitor) if an echocardio‐graphic response was identified. At the 4‐month time period, each investigator was asked to decide whether he or she thought his or her patient was receiving placebo or taurine/ carnitine, based on presence or absence of clinical and echocar‐diographic improvement. Unblinding then occurred, and dogs receiving placebos were switched to taurine and carnitine supplementation and followed monthly for 4 additional months. All dogs were reexamined 6 months after starting supplementation; survival time and cause of death were recorded for each dog. Data from 3 dogs were not included because of multiple protocol violations. Each dog had a plasma taurine concentration <50 nmol/mL (mean ±SD for the group 15 ± 17 nmol/ mL) at baseline; normal range, 50–180 nmol/mL. The plasma taurine concentration did not exceed 50 nmol/mL at any time in the dogs receiving placebos (n = 5), but increased to 357 ± 157 nmol/mL (range 140–621 nmol/mL) during taurine and carnitine supplementation (n = 11). Plasma carnitine concentration was within, only slightly below, or slightly above reported limits of normality at baseline (29 ± 15 μmol/L); did not change during placebo administration; and increased significantly during supplementation (349 ±119 μmol/L; n = 11). Echocardiographic variables did not change during placebo administration. During supplementation, left ventricular end‐dia‐stolic and end‐systolic diameters, and mitral valve E point‐to‐septal separation decreased significantly in both groups. Shortening fraction increased significantly but not into the normal range. Echocardiographic variables remained improved at 6 months. All dogs were successfully weaned off furosemide, an angiotensin converting enzyme inhibitor, and digoxin once an echocardiographic response was identified. Nine of the dogs have died since the onset of the study in 1992. One dog died of recurrence of DCM and heart failure 31 months after starting supplementation; six dogs died of noncardiac causes. Two dogs developed degenerative mitral valve disease and died of complications of this disease. Dogs less than 10 years of age lived for 46 ± 11 months, whereas dogs older than 10 years of age lived for 14 ± 7 months. Two of the 11 dogs were alive at the time of publication, having survived for 3.5 and 4.5 years, respectively. We conclude that ACS with DCM are taurine‐deficient and are responsive to taurine and carnitine supplementation. Whereas myocardial function did not return to normal in most dogs, it did improve enough to allow discontinuation of cardiovascular drug therapy and to maintain a normal quality of life for months to years.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Kittleson, MD and Keene, B and Pion, PD and Loyer, CG and Beardow, AW and Knight, DH and Bonagura, JD and Burgener, DC and DeLellis, LA and Goullaud, R and et al.}, year={1997}, pages={204–211} } @article{keene_1996, title={Management of canine dilated cardiomyopathy}, volume={21}, number={1}, journal={Canine Practice (Santa Barbara, Calif. : 1990)}, author={Keene, B. W.}, year={1996}, pages={27} } @article{keene_flammer_1991, title={ECG of the month}, volume={198}, number={3}, journal={Journal of the American Veterinary Medical Association}, author={Keene, B. W. and Flammer, K.}, year={1991}, pages={408} }