Preliminary investigation of angiotensin-converting enzyme inhibitors and pimobendan in horses
Sanches Madeira Afonso, Tiago
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The overall objective of these studies was to characterize the pharmacodynamic effects of angiotensin-converting enzyme (ACE) inhibitors and pimobendan in horses. Both are considered standard of care in the management of congestive heart failure in dogs but the lack of data in horses has prevented the rationale use of these drugs in this species. First, the pharmacodynamic effects of 4 ACE inhibitors (benazepril, ramipril, quinapril, and perindopril) were investigated in healthy horses. Of these, oral benazepril (0.5 mg/kg) was the most effective at inhibiting serum ACE activity and its effect was not affected by feeding. In an attempt to determine the ideal dose and dosing interval for a clinical trial in horses, the lowest tested dose of benazepril that resulted in optimal attenuation in the response of systolic blood pressure to exogenous administration of angiotensin I administration was determined. The percentage of inhibition after administration of benazepril at 1.0 mg/kg was significantly greater than that achieved after 0.5 mg/kg but not significantly different from that achieved at higher doses. It was concluded that oral benazepril at a dose of 1.0 mg/kg every 12 h would be recommended for future investigations. Third, a prospective randomized double-blinded placebo-controlled trial was conducted to assess the echocardiographic and hormonal changes in response to 28 days of oral benazepril in horses with volume overload caused by mitral or aortic valve insufficiency. Treatment with benazepril resulted in a significant increase in cardiac output and fractional shortening, suggesting a decrease in afterload. Despite profound serum ACE inhibition, renin, angiotensin II, aldosterone, and chemistry variables were not significantly different between treatment groups or time points. Finally, the cardiovascular effects of intravenous (IV) and intragastric (IG) pimobendan at a dose of 0.25 mg/kg were investigated in healthy adult horses. Both IV and IG pimobendan had significant chronotropic effects but only the IV formulation had the desired inotropic effects. Collectively, the work reported herein provides the data necessary for the rationale use of benazepril in horses with valvular insufficiency and provides preliminary data for future investigations regarding the use of pimobendan in horses.