SELECTIVE SUPPRESSION OF NEURAL EXCITATION BY TETRODOTOXIN INJECTED INTO THE CANINE ATRIOVENTRICULAR NODE ARTERY

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

Effects of tetrodotoxin (TTX) on atrioventricular (A-V) conduction were studied by selective injection into the posterior septal artery of the canine heart in situ with the vagosympathetic trunks and the cardiac nerves cut bilaterally. After section of both cardiac nerves, the A-V conduction time was significantly prolonged. Small doses of TTX selectively blocked excitation of parasympathetic or sympathetic nerve fibers sparing cardiac tissues concerned in A-V conduction. Doses of TTX to cause 50% inhibition of the positive dromotropic effect of stimulation of the left cardiac nerves were approximately 3 nmol, whereas those to produce 50% inhibition of the negative effect of vagal stimulation were approximately 1 nmol. This suggests that the vagus nerve is more susceptible to TTX than the sympathetic nerve. Continuous infusion of TTX at a rate of 0.3 or 1 nmol/min maintained complete nerve block without any effects on A-V conduction, during which the negative dromotropic effect of methacholine, positive effects of l-norepinephrine and tyramine were hardly affected but the biphasic effect of nicotine was completely abolished. Large doses of TTX, 10 to 100 nmol, increased the A-V conduction time in a dose-dependent manner, and with 100 nmol of TTX ventricular fibrillation occurred in four out of nine preparations suddenly after the prolonged A-V conduction time reached a plateau.