Influence of AQ-A39, a bradycardic agent, on cardiovascular responses to isoproterenol in the anesthetized dog.

The effects of AQ-A39, a selective bradycardic agent, on cardiovascular responses to beta-adrenergic stimulation with isoproterenol were investigated in open-chest, anesthetized dogs. Verapamil and timolol were also studied and compared with AQ-A39. All three compounds decreased basal heart rate and significantly decreased the chronotropic potency of isoproterenol. At 1.0 and 3.0 mg/kg, AQ-A39 reduced the relative potency of isoproterenol on heart rate to 0.730 and 0.312, respectively (control potency = 1.0). AQ-A39 enhanced the isoproterenol-mediated increases in cardiac output without affecting the potency of isoproterenol on mean arterial blood pressure or left ventricular dP/dtmax. Timolol reduced the potency of isoproterenol on all parameters studied. Verapamil decreased the left ventricular dP/dtmax response but did not change the mean arterial blood pressure or cardiac output responses to isoproterenol. Therefore, AQ-A39 demonstrated greater selectivity for inhibiting the chronotropic responses to beta-adrenergic stimulation in vivo than verapamil or timolol. Selective inhibition of positive chronotropic but not positive inotropic responses, as observed with AQ-A39, could be beneficial in the treatment of ischemic heart disease.