Electrophysiologic Effects of Propranolol on the Human Heart

Effects of propranolol (10(-9) to 10(-4) Gm/ml) on various electrophysiologic properties of human papillary muscles obtained from patients undergoing corrective open heart surgery were studied to have an insight into the mechanism of its antiarrhythmic activity in man. Propranolol (10(-8) to 10(-6) Gm/ml) produced significant decreases in the action potential duration, effective refractory period and dv/dt of depolarization phase of action potential without significantly affecting the resting potential and amplitude of action potential. These effects were concentration dependent. High concentration (10(-4) Gm/ml) of propranolol not only produced greater decreases in the above parameters but also reduced the resting potential and amplitude of action potential. Although propranolol decreased both the action potential duration and effective refractory period, the shortening of the action potential duration was greater than the shortening of the effective refractory period. It shifted the membrane responsiveness curve to the right and down. It produced frequency dependent decreases in the dv/dt of phase 0 of action potential and the rate of repolarization. Propranolol also increased the threshold of stimulation. Propranolol produced electrophysiologic changes in the human myocardium qualitatively similar to those in canine myocardium. The probable mechanism of its antiarrhythmic activity in man has been discussed.