DROMOTROPIC EFFECTS OF OPTICAL ISOMERS OF BETA BLOCKERS ON THE CROSS-CIRCULATED CANINE ATRIOVENTRICULAR NODE PREPARATION

¹ Department of Pharmacology and Experimental Therapeutics, Tohoku University School of Medicine, Sendai, Japan

The effects of l-norepinephrine (l-NE) and both optical isomers of propranolol and alprenolol on atrioventricular (A-V) conduction were studied in the isolated and cross-circulated A-V node preparation of the dog (consisting of the right atrium and the ventricular septum). The A-V conduction time was measured by an A-V interval graph to which atrial and ventricular electrograms were provided. The right atrium was paced at 2.5 Hz, at which the A-V conduction time was about 125 msec. All drugs were injected into the posterior septal (A-V node) artery. l-NE (0.01-3 nmol) caused does-dependent decreases in the A-V conduction time down to 80 msec and in higher doses caused A-V nodal tachycardia. The l-isomers of propranolol and alprenolol fully antagonized the positive dromotropic effect of l-NE at an antagonist/agonist ratio of 30, while their d-isomers antagonized only about 10% of the positive dromotropic effect at that ratio. When compared at the dose level causing 50% antagonism, the d-isomers were 100 to 300 times less potent than the l-isomers. In doses above 100 nmol, all of these compounds caused an increase in the A-V conduction time, which was reversible. In this dose range, there were no significant differences in negative dromotropic action between the l- and the d-isomers or between propranolol and alprenolol. This indicates that the negative dromotropic action does not relate to beta adrenergic blockade.