The Myocardial Depressant Effect of Beta-Receptor Blocking Agents

dl-Propranolol, d-propranolol, and practolol were administered in increasing doses to conscious dogs before and after acute coronary artery occlusion. dl-Propranolol and practolol caused dose-dependent decreases in cardiac output, stroke volume, stroke work, and maximum rate of left ventricular pressure rise before and after coronary artery occlusion. These parameters were reduced 25–40% after the largest cumulative doses—1.43 mg/kg for dl-propranolol and 52 mg/kg for practolol—were administered. The degree of beta-receptor blockade increased in proportion to the logarithm of plasma drug concentration. After occlusion, both drugs produced identical decreases in cardiac output at equivalent degrees of beta-receptor blockade. Neither drug affected resting heart rate before infarction, and neither drug reduced the tachycardia induced by coronary artery occlusion; this tachycrotic response probably resulted from cardiac vagal withdrawal. Mean systemic arterial blood pressure and total peripheral vascular resistance increased following beta-receptor blockade before infarction, most likely because of increased peripheral vascular alpha-adrenergic activity. These two effects did not occur after coronary artery occlusion, probably because vascular alpha-adrenergic activity had already been stimulated. d-Propranolol produced none of these effects. We concluded that the cardiodepressant effect of beta-receptor blocking agents in the doses administered was caused by their inhibition of endogenous sympathetic tone to the heart rather than by their quinidinelike action.