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Hemodynamic effects of orally administered carvedilol in healthy conscious dogs

Jonathan A. AbbottDepartment of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

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Richard V. BroadstoneDepartment of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

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Daniel L. WardDepartment of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

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R. Lee PyleDepartment of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

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Abstract

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. (Am J Vet Res 2005;66:637–641)

Abstract

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. (Am J Vet Res 2005;66:637–641)