Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol

Five patients who had received a transplanted human heart 1 to 3 years previously were studied to determine the effects of norepinephrine, isoproterenol and propranolol on the atrioventricular (A-V) conduction system. Using the His bundle technique, atrial, His bundle and ventricular electrograms were recorded, and central aortic pressure was monitored during the administration of these drugs. Norepinephrine was given by continuous infusion to four patients in doses ranging from 4 to 8 mug/min, with the systolic arterial pressure increasing by an average of 72 mm Hg. Concomitantly, there was an average increase in the rate of the donor atrium of 32 beats/min, and a reflex slowing of the recipient atrium of 23 beats/min. The A-H interval shortened by an average of 27 msec. Isoproterenol dose-response curves were performed in three patients, with the maximal dose being 5.2 mug by intravenous bolus infusion. The rate of the donor atrium increased by an average of 40 beats/min, and that of the recipient atrium by 18 beats/min. The A-H time shortened by an average of 25 msec, with a drop in systolic blood pressure averaging 23 mm Hg. Propranolol (7 mg intravenously) was given to three patients and the peak doses of norepinephrine and isoproterenol were again infused. Beta adrenergic blockade was achieved at this dose of propranolol since there was only a minimal increase in the donor atrial rate after infusion of the drug. The A-H interval was not altered by catecholamine infusion after achievement of beta blockade. However, the levels of systolic hypertension noted after infusion of norepinephrine was not altered by propranolol. The denervated transplanted human heart appears to respond normally to norepinephrine and isoproterenol, and the electrophysiologic effects of these agents are blocked by propranolol. Extensive investigative work in the denervated canine model has demonstrated the presence of the alpha and beta cardiovascular receptors. Although the automonic nervous system is important in cardiac performance, this work is the first validation in man that (1) the functional integrity of the beta receptor is maintained even when the autonomic nerves are absent, and (2) the intrinsic properties of the sinus and atrioventricular nodes are the keystone in stabilizing cardiac electrophysiology after denervation.