Hemodynamic effects of orally administered carvedilol in healthy conscious dogs

Objective - To evaluate the hemodynamic effects of orally administered carvedilol in healthy dogs with doses that might be used to initiate treatment in dogs with congestive heart failure. Animals - 24 healthy dogs. Procedure - Dogs were randomly allocated to receive carvedilol PO at a dose of 1.56, 3.125, or 12.5 mg, twice daily for 7 to 10 days; 6 dogs served as controls. Investigators were blinded to group assignment. Hemodynamic variables were recorded prior to administration of the drug on day 1 and then 2, 4, and 6 hours after the morning dose on day 1 and days 7 to 10. Change in heart rate after IV administration of 1 μg of isoproterenol/kg and change in systemic arterial blood pressure after IV administration of 8 μg of phenylephrine/kg were recorded 2 and 6 hours after administration of carvedilol. Results - Administration of carvedilol did not significantly affect resting hemodynamic variables or response to phenylephrine. The interaction of day and carvedilol dose had a significant effect on resting heart rate, but a significant main effect of carvedilol dose on resting heart rate was not detected. Increasing carvedilol dose resulted in a significant linear decrease in heart rate response to isoproterenol. Conclusions and clinical relevance - In healthy conscious dogs, orally administered carvedilol at mean doses from 0.08 to 0.54 mg/kg given twice daily did not affect resting hemodynamics. Over the dose range evaluated, there was a dose-dependent attenuation of the response to isoproterenol, which provided evidence of β-adrenergic receptor antagonism.