Hemodynamic effects of two beta-adrenergic blocking drugs in anesthetized intact dogs

The hemodynamic effects of two beta-blocking drugs were evaluated in intact dogs anesthetized with chloralose-urethane. Nethalide (5 mg. per kilogram intravenously in 15 minutes) significantly increased cardiac output, heart rate, and stroke volume, and decreased end-systolic volume/end-diastolic volume ratio and systemic vascular resistance. The decrease in calculated end-systolic force per unit of end-systolic circumference suggests a negative inotropic effect. The preponderant effect of the drug was arterial dilatation, which cannot be explained by beta-adrenergic blockade. Better ventricular emptying was probably secondary to decreased afterload, since end-diastolic volume did not change.The chief site of activity of propranolol (0.5 mg. per kilogram intravenously in 5 minutes) was on the myocardium; left ventricular end-diastolic pressure increased without a change in end-diastolic volume, which indicates that diastolic distensibility was reduced. In addition, mean circumferential shortening velocity decreased, which suggests a negative inotropic effect; end-diastolic volume and stroke work were unchanged, and end-systolic force per unit of end-systolic circumference increased. The latter is perhaps due to an increased contribution of elasticity to end-systolic tension. We do not know whether these results are due to inhibition of beta-adrenergic activity or to direct effects on the myocardium.