@article{kaplan_rivas_walker_grubb_farrell_fitzgerald_kennedy_pjauregui_crofton_pmclaughlin_et al._2023, title={Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic results of the RAPACAT trial}, volume={261}, ISSN={["1943-569X"]}, url={https://publons.com/wos-op/publon/65523912/}, DOI={10.2460/javma.23.04.0187}, abstractNote={Abstract

OBJECTIVE
Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.


ANIMALS
43 client-owned cats with subclinical HCM.


METHODS
Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.


RESULTS
No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.


CLINICAL RELEVANCE
Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.
}, number={11}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Kaplan, Joanna L. and Rivas, Victor N. and Walker, Ashley L. and Grubb, Louise and Farrell, Aisling and Fitzgerald, Stuart and Kennedy, Susan and Pjauregui, Carina E. and Crofton, Amanda E. and Pmclaughlin, Chris and et al.}, year={2023}, month={Nov}, pages={1628–1637} }
 @article{mclaughlin_marks_dorman_motsinger-reif_hanel_2017, title={Thromboelastographic monitoring of the effect of unfractionated heparin in healthy dogs}, volume={27}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12526}, abstractNote={AbstractObjectiveTo characterize the correlation between thromboelastography (TEG) variables using strong activators and anti‐Xa (AXa) activity in healthy dogs administered subcutaneous unfractionated heparin (UFH).DesignProspective experimental study.SettingUniversity research facility.AnimalsEight adult random‐source male dogs.InterventionDogs were randomized to receive subcutaneous UFH at 200, 250, or 300 IU/kg every 8 hours for a total of 10 injections. Blood samples were collected at time 0 (preheparin) and 3, 6, and 8 hours after the 1st (Day 1) and 10th (Day 4) UFH injection.  After the 8‐hour blood sample was obtained on day 4, a 100 IU/kg IV bolus of UFH was administered and an additional blood sample was collected 1 hour later (hour 9). AXa activity, activated partial thromboplastin time (aPTT), and TEG (with up to 5 activators) were performed at each time point.  Modes of activation for TEG included  recalcified (Ca), Ca with heparinase (CaH), CaH and tissue factor 1:3600 (CTF3600H), Ca with tissue factor 1:100 (CTF100), and RapidTEG. Spearman rank correlations were calculated for each of the aforementioned parameters and the AXa activity. P‐values were corrected for multiple comparisons with a Bonferroni correction.Measurements and Main ResultsSignificant correlations were found between AXa activity and the TEG R values generated with CTF100 (R = 0.83, P ≤ 0.0001) and RapidTEG (R = 0.90, P < 0.0001), as well as both forms of aPTT measurement (R = 0.86 and 0.84, P < 0.0001).ConclusionsThis study demonstrates that TEG variables derived using robust activation correlate with AXa activity as well as aPTT and have the potential to be used for monitoring UFH therapy in healthy dogs.  Future studies are warranted to evaluate its diagnostic utility in critically ill animals.}, number={1}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={McLaughlin, Christopher M. and Marks, Steven L. and Dorman, David C. and Motsinger-Reif, Alison and Hanel, Rita M.}, year={2017}, pages={71–81} }