Comparison of cardiovascular responses to the bradycardic drugs, alinidine, AQ-A 39, and mixidine, in the anesthetized dog.

Cardiovascular responses to three bradycardic drugs, alinidine, AQ-A 39, and mixidine, were studied in open-chest, anesthetized dogs. All three drugs produced a dose-related decrease in heart rate at 0.3-10 mg/kg i.v. At 2.5 mg/kg i.v., spontaneous heart rates were decreased by 59 +/- 7, 52 +/- 6, and 39 +/- 6 beats/min with alinidine, AQ-A 39, and mixidine, respectively. The sinus node was an important site of action, because direct injection of alinidine, AQ-A 39, or mixidine to the sinus node via the sinus node artery (50 micrograms) elicited a negative chronotropic response. On systemic administration, total peripheral resistance was significantly increased with alinidine, significantly decreased with AQ-A 39, and not affected with mixidine. Increases in stroke volume accompanied bradycardic responses to AQ-A 39 and mixidine, and were prevented when heart rate was held constant by electrical pacing. Despite the production of similar effects on heart rate, AQ-A 39 differed from alinidine and mixidine in that it did not depress cardiac contractility in dogs with spontaneous heart rates. Therefore, all three drugs were effective and relatively selective in reducing heart rate; however, responses at the systemic vasculature and myocardium differed.