Sustained cardiac beta adrenoceptor blockade in vitro and increased vulnerability to aconitine-induced arrhythmias in vivo after propranolol withdrawal in rats

A Hedberg, O Isaksson and B Lundgren

The present study was undertaken in order to investigate the possibility of cardiac hypersensitivity to norepinephrine (NE) after propranolol withdrawal in rats. The effect of NE was studied on heart rate and left intraventricular pressure development (maximal dP/dt) in the isolated perfused heart at various time periods after termination of the propranolol feeding. Also, the influence of propranolol withdrawal on vulnerability to aconitine-induced arrhythmias in vivo was evaluated in anesthetized rats. No hypersensitivity to NE was seen in the perfused rat heart 1 and 3 days after propranolol withdrawal. Rather, a depressed response to NE was registered suggesting a long half-life for the disappearance of beta adrenoceptor blockade. Increased vulnerability to aconitine-induced arrhythmias was observed 1 and 3 days after treatment with propranolol had ceased. Rats receiving propranolol continuously until experimentation exhibited an elevated threshold to aconitine-induced arrhythmias. These data indicate that a hypothetical rebound phenomenon after withdrawal of propranolol is not associated with an increase in mechanical performance of the heart in response to NE. A decreased threshold for development of arrhythmias appears, however, to be at hand, perhaps due to an inbalance in the transmembrane sodium flux in the heart in the early time course after propranolol withdrawal.

Volume 214, Issue 3, pp. 664-669, 09/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics