Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats.
OBJECTIVE
To determine the pharmacodynamic effects of oral ivabradine in cats.


METHODS
Eight healthy, adult domestic short hair cats.


METHODS
Each cat underwent four study periods of 24 h, receiving either one dose of placebo or ivabradine (0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) in a single-blind randomized crossover study. Clinical tolerance was assessed hourly for the first 8 h, at 12 h, and at the end of the 24-h study period. Heart rate and blood pressure were monitored continuously for 18-24 h via radiotelemetry after each treatment. Response to stress (acoustic startle) was studied before (t = 0) and after treatment (t = 4 h). Statistical comparisons were made using a linear mixed models and 1-way and 2-way repeated measures ANOVA.


RESULTS
Heart rate (min(-1)) decreased significantly (P < 0.05) in a dose-dependent manner with peak negative chronotropic effects observed 3 h after ivabradine (mean ± SD; placebo, 144 ± 20; ivabradine 0.1 mg/kg, 133 ± 22; ivabradine 0.3 mg/kg, 112 ± 20; and ivabradine 0.5 mg/kg, 104 ± 11). Heart rate (min(-1)) was still reduced (P < 0.05) 12 h after ivabradine (0.3 mg/kg; 128 ± 18 and 0.5 mg/kg; 124 ± 16) compared to placebo (141 ± 21). The tachycardic response to acoustic startle was significantly (P < 0.01) blunted at all 3 doses of ivabradine. Myocardial oxygen consumption estimated by the rate-pressure product was significantly reduced (P < 0.05) for all doses of ivabradine. No effect of ivabradine on systolic, diastolic, and mean blood pressure was identified and no clinically discernable side effects were observed.


CONCLUSIONS
These findings indicate that a single oral dose of ivabradine predictably lowers heart rate, blunts the chronotropic response to stress, and is clinically well tolerated in healthy cats. This makes ivabradine potentially interesting in the treatment of feline heart disease where ischemia is of pathophysiologic importance.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Richard E
RE
Cober
Karsten E
KE
Schober
Tony C A
TC
Buffington
Xiaobai
X
Li
Sabine C
SC
Riesen
John D
JD
Bonagura
D000284:Administration, Oral; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats / Q000502:physiology*; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D000077550:Ivabradine; D008297:Male; D008991:Monitoring, Physiologic / Q000662:veterinary; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D016037:Single-Blind Method; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors
D001552:Benzazepines; D002316:Cardiotonic Agents; D000077550:Ivabradine