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
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)
OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours.
ANIMALS 20 healthy dogs.
PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 μg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi.
RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr.
CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.