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.


METHODS
24 healthy dogs.


METHODS
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 1microg of isoproterenol/kg and change in systemic arterial blood pressure after IV administration of 8 microg 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
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 beta-adrenergic receptor antagonism.
Abbott
Jonathan A
JA
Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442, USA.
Broadstone
Richard V
RV
Ward
Daniel L
DL
Pyle
R Lee
RL
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004285:Dogs / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000662:veterinary; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011897:Random Allocation
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D010656:Phenylephrine; D007545:Isoproterenol