@article{ames_vaden_atkins_palerme_langston_grauer_shropshire_bove_webb_2022, title={Prevalence of aldosterone breakthrough in dogs receiving renin-angiotensin system inhibitors for proteinuric chronic kidney disease}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16573}, abstractNote={AbstractBackgroundThe influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin‐angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP) has not been determined in dogs.ObjectivesDetermine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment.AnimalsFifty‐six client‐owned dogs with CKDP and 31 healthy client‐owned dogs.MethodsProspective, multicenter, open‐label clinical trial. Dogs were treated with an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone‐to‐creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein‐to‐creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT).ResultsThirty‐six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2‐2.2).Conclusions and Clinical ImportanceAldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Ames, Marisa K. and Vaden, Shelly L. and Atkins, Clarke E. and Palerme, Jean-Sebastien and Langston, Catherine E. and Grauer, Gregory F. and Shropshire, Sarah and Bove, Christina and Webb, Tracy}, year={2022}, month={Nov} }
 @article{ames_vanvranken_evans_atkins_2020, title={Non-Arsenical heartworm adulticidal therapy using topical moxidectin-imidacloprid and doxycycline: A prospective case series}, volume={282}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2020.109099}, abstractNote={Abstract This prospective case series evaluated the adulticidal efficacy of topical 10 % moxidectin/2.5 % imidacloprid (M/I; Advantage Multi®, Bayer, Shawnee Mission, KS, USA) and doxycycline in dogs with naturally occurring heartworm infection (HWI). Twenty-two dogs with HWI whose owners declined melarsomine were treated with M/I at the preventive dosage twice monthly for 90 days then monthly thereafter and doxycycline (median [interquartile range; IQR] dosage 12.6 [12.0–16.1] mg/kg/day) for the first 15 days. Although strict activity restriction was not imposed, owners were asked to prevent their dogs from exercising strenuously. This protocol was referred to as the MOXY protocol. Antigen testing was performed every 30–60 days, until dogs had ‘no antigen detected’ (NAD). Twenty-one of the 22 dogs ultimately converted to NAD by 434 days (median [IQR]), 234 (179–303). One dog remained positive 701 days after MOXY initiation and was considered a treatment failure. All sera which converted to NAD on HW antigen testing were retested after heat-treatment. Twelve dogs had NAD on the heat-treated test on the same day as having their first NAD on the conventional test. Six of 9 dogs testing positive after heat-treatment were retested and all 6 had NAD on a heat-treated test within 2–3 months. Microfilaremia was cleared in all 8 dogs re-tested. Four dogs required treatment for cough, thought due to heartworm (HW) death, an average of 89 days after initiation of MOXY. This cough was most likely due to pneumonitis with heartworm-pulmonary thromboembolism. One dog required hospitalization for 24 -h and recovered fully with corticosteroid therapy and supportive care and 2 dogs were treated in an outpatient fashion with steroids. The MOXY protocol was tolerated and 96 % (21/22) of dogs converted to NAD, though 2 dogs required greater than 1 year to achieve this result. Nonaresenical-adulticide therapy may result in pneumonitis and heartworm-pulmonary thromboembolism at unpredictable times, potentially months after initiation of macrocyclic lactone therapy and exercise restriction should be considered when using a nonarsenical protocol. Although not currently recommended by the American Heartworm Society (AHS), non-arsenical strategies are in use and the goal of this study was to evaluate the efficacy, duration of therapy, and safety of an accelerated dosing protocol of M/I with doxycycline.}, journal={VETERINARY PARASITOLOGY}, author={Ames, Marisa K. and VanVranken, Philip and Evans, Chelsea and Atkins, Clarke E.}, year={2020}, month={Jun} }
 @article{ames_atkins_2020, title={Treatment of dogs with severe heartworm disease}, volume={283}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2020.109131}, abstractNote={Fortunately, the majority of dogs diagnosed with heartworm infection are asymptomatic (or have only mild symptoms such as intermittent cough) and go through adulticide therapy without complication. Complications occurring with heartworm infection and during its treatment most often directly reflect the pulmonary vascular and parenchymal injury inflicted by Dirofilaria immitis. Clinical signs may include exercise intolerance, frequent cough, hemoptysis, tachypnea, and dyspnea. Severe manifestations such as heart failure and caval syndrome may prove fatal. Acute hypersensitivity reactions after initiation of macrocyclic lactone preventive therapy in microfilaremic dogs or after melarsomine injection during adulticide therapy do occur, but are uncommon. This article reviews complications associated with heartworm infection.}, journal={VETERINARY PARASITOLOGY}, author={Ames, Marisa K. and Atkins, Clarke E.}, year={2020}, month={Jul} }
 @misc{ames_atkins_pitt_2019, title={The renin-angiotensin-aldosterone system and its suppression}, volume={33}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15454}, abstractNote={Chronic activation of the renin‐angiotensin‐aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro‐fibrotic, ‐inflammatory, and ‐hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Ames, Marisa K. and Atkins, Clarke E. and Pitt, Bertram}, year={2019}, pages={363–382} }
 @article{ames_atkins_eriksson_hess_2017, title={Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease}, volume={19}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2017.03.001}, abstractNote={Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation.This study includes 39 dogs with myxomatous mitral valve disease. A UAldo:C cut-off definition (derived from a normal population of healthy, adult, and client-owned dogs) was used to determine the prevalence of ABT in this population. Spearman analysis and univariate logistic regression were used to evaluate the relationship between UAldo:C and ABT (yes/no) and eight variables (age, serum K+ concentration, serum creatinine concentration, ACEI therapy duration and ACEI dosage, furosemide therapy duration and furosemide dosage, and urine sample storage time). Finally, the UAldo:C in dogs receiving spironolactone, as part congestive heart failure (CHF) therapy, was compared to dogs with CHF that were not receiving spironolactone.The prevalence of ABT was 32% in dogs with CHF and 30% in dogs without CHF. There was no relationship between either the UAldo:C or the likelihood of ABT and the eight variables. Therapy with spironolactone lead to a significant elevation of the UAldo:C.Using the UAldo:C and a relatively stringent definition of ABT, it appears that incomplete RAAS blockade is common in dogs with MMVD receiving an ACEI. The prevalence of ABT in this canine population mirrors that reported in humans. While the mechanism of ABT is likely multifactorial and still poorly understood, the proven existence of ABT in dogs offers the potential to improve the prognosis for MMVD with the addition of a mineralocorticoid receptor blocker to current therapeutic regimens.Approximately 30% of dogs being treated for heart disease and CHF satisfied the definition of ABT. Identifying patient subpopulations experiencing ABT may help guide future study design and clinical decision-making.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Ames, M. K. and Atkins, C. E. and Eriksson, A. and Hess, A. M.}, year={2017}, month={Jun}, pages={218–227} }
 @article{ames_atkins_lee_lantis_zumbrunnen_2015, title={Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs}, volume={76}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.76.12.1041}, abstractNote={Abstract
OBJECTIVE To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS).
ANIMALS 6 healthy Beagles.
PROCEDURES 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days −1, 3, and 7; serum aldosterone concentration on days −2, −1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days −2, −1, 1, 3, and 7.
RESULTS High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Ames, Marisa K. and Atkins, Clarke E. and Lee, Seunggon and Lantis, Andrea C. and zumBrunnen, James R.}, year={2015}, month={Dec}, pages={1041–1050} }
 @article{lantis_ames_werre_atkins_2015, title={The effect of enalapril on furosemide-activated renin-angiotensin-aldosterone system in healthy dogs}, volume={38}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12216}, abstractNote={Studies in our laboratory have revealed that furosemide‐induced RAAS activation, evaluated via the urine aldosterone‐to‐creatinine ratio (UAldo:C), was not attenuated by the coadministration of benazepril, while enalapril successfully suppressed amlodipine‐induced urinary aldosterone excretion. This study was designed to evaluate the efficacy of enalapril in suppressing ACE activity and furosemide‐induced circulating RAAS activation. Failure to do so would suggest that this failure may be a drug class effect. We hypothesized that enalapril would suppress ACE activity and furosemide‐induced circulating RAAS activation. Sixteen healthy hound dogs. The effect of furosemide (2 mg/kg PO, q12 h; Group F) and furosemide plus enalapril (0.5 mg/kg PO, q12 h; Group FE) on circulating RAAS was determined by plasma ACE activity, 4–6 h post‐treatment, and urinary A:C on days −1, −2, 1, 4, and 7. There was a significant increase in the average urine aldosterone‐to‐creatinine ratio (UAldo:C) after administration of furosemide (P < 0.05). Enalapril inhibited ACE activity (P < 0.0001) but did not significantly reduce aldosterone excretion. A significant (P < 0.05) increase in the UAldo:C was maintained for the 7 days of the study in both groups. Enalapril decreased plasma ACE activity; however, it did not suppress furosemide‐induced RAAS activation, as determined by the UAldo:C. While enalapril blunts ACE activity, the absence of circulating RAAS suppression may be due to angiotensin II reactivation, alternative RAAS pathways, and furosemide overriding concurrent ACE inhibition, all indicating the existence of aldosterone breakthrough (ABT). Along with similar findings with benazepril, it appears that failure to suppress aldosterone suppression with furosemide stimulation may be a drug class effect. The discrepancy between the current data and the documented benefits of enalapril likely reflects the efficacy of this ACE inhibitor in suppressing tissue RAAS, variable population responsiveness to ACE‐inhibition, and/or providing additional survival benefits, possibly through as yet unknown mechanisms.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lantis, A. C. and Ames, M. K. and Werre, S. and Atkins, C. E.}, year={2015}, month={Oct}, pages={513–517} }
 @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{schneider_ames_dicicco_savage_atkins_wood_gookin_2015, title={Recovery of normal esophageal function in a kitten with diffuse megaesophagus and an occult lower esophageal stricture}, volume={17}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x14542451}, abstractNote={ An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture. }, number={6}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Schneider, Jaycie and Ames, Marisa and DiCicco, Michael and Savage, Mason and Atkins, Clarke and Wood, Michael and Gookin, Jody L.}, year={2015}, month={Jun}, pages={557–561} }
 @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{ames_atkins_lantis_were_2013, title={Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs}, volume={74}, DOI={10.2460/ajvr.74.8.1084}, abstractNote={Abstract
Objective—To determine whether a high dosage of pimobendan, when administered concurrently with moderate-dosage furosemide to healthy dogs, would activate the renin-angiotensin-aldosterone system (RAAS) more than furosemide alone.
Animals—12 healthy dogs.
Procedures—6 dogs received furosemide (2.0 mg/kg, PO, q 12 h) only, as an RAAS activator, for 10 days. The other 6 dogs received furosemide (2.0 mg/kg, PO, q 12 h) and pimobendan (0.6 mg/kg, PO, q 12 h) for 10 days. The effect of these drugs on the RAAS was determined by measurement of the aldosterone-to-creatinine ratio (A:C) in urine collected in the morning and evening of study days −2, −1, 1, 5, and 10.
Results—Although there was an increase in the urine A:C during the study period in both groups, it was significant only for dogs that received both drugs. The urine A:C only differed significantly between groups on day 1, at which time A:C was greater in the group that received both drugs.
Conclusions and Clinical Relevance—High-dosage pimobendan administration neither substantially suppressed nor potentiated the RAAS when administered with furosemide in healthy dogs.}, number={8}, journal={American Journal of Veterinary Research}, author={Ames, M. K. and Atkins, C. E. and Lantis, A. C. and Were, S. R.}, year={2013}, pages={1084–1090} }