Objective: Dosing intervals of 12 and 24 hours for atenolol have been recommended, but an evidentiary basis is lacking. To test the hypothesis that repeated, once-daily oral administration of atenolol attenuates the heart rate response to isoproterenol for 24 hours, we performed a double-blind, randomized, placebo-controlled cross-over experiment. Animals: Twenty healthy dogs Procedures: Dogs were randomly assigned to receive either placebo (P) and then atenolol (A), [1 mg/kg PO q24h] or vice versa. Treatment periods were 5-7 days; time between periods was 7 days. Heart rates (bpm) at rest (HRr) and during constant rate [0.2 μg/kg/min] infusion of isoproterenol (HRi) were electrocardiographically obtained 0, 0.25, 3, 6, 12, 18, and 24 hours after final administration of drug or placebo. A mixed model ANOVA was used to evaluate the effects of treatment (Tr), time after drug or placebo administration (t), interaction of treatment and time (Tr*t) as well as period and sequence on HRr and HRi. Results: Sequence or period effects were not detected. There was a significant effect of Tr (p <0.0001) and Tr*t (p <0.0001) on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares means ± SE, A: 146±5 bpm, P: 208±5 bpm); the effect at 24 hours was small (A: 193±5, P: 206±5). Atenolol had a small but significant effect (p <0.0001) on HRr. Conclusions and Clinical Relevance: The results of this study support a dosing interval that is less than 24 hours. / MS / This thesis was designed to test the effects of the drug atenolol on heart rate in dogs. Atenolol is used to reduce the heart rate of dogs with cardiovascular disease. The study used 20 dogs that were given oral capsules in both a placebo (no drug) and atenolol phase of the experiment. The study was designed to control for other causes of slower heart rate and make sure that the investigator did not know which treatment was given to a dog. Placebo dogs had a high heart rate response to the drug isoproterenol whereas atenolol treated dogs had a statistically significant lower heart rate response compared to placebo over a 24 hours period of time. The difference between treatments was small after 24 hours and further work is needed to determine the best time interval between doses of medication.

Abstract Not Provided. / Thesis / Master of Science (MSc)