Dual Effect of Verapamil on Sinus Node Function in Man

Abstract

Verapamil is the prototype of slow-channel inhibiting drugs which exert their effect mainly on the sinus and atrioventricular node (Bayer et al., 1975; Kohlhardt et al., 1976; Wit and Cranefield, 1974; Zipes and Fischer, 1974). Experimental studies in the isolated sinoatrial preparation have shown that it has a marked depressant effect on sinus node activity (Bayer et al., 1975; Chiba, 1975; Obayashi et al., 1975; Wit and Cranefield, 1974). Verapamil causes a decrease in the amplitude of the action potential and a small decline in the maximal diastolic potential (Wit and Cranefield, 1974). Sinus node discharge is decreased and may be followed by subtreshold oscillations leading to irregular failure of impulse initiation (Bayer et al., 1975; Kohlhardt et al., 1976; Wit and Cranefield, 1974). Selective injections of verapamil into the right coronary artery of the dog also caused a decrease in heart rate with appearance of nodal rhythms which was not the case if it was administered intra- venously (Garvey, 1969). In contrast to the experiments in isolated preparations, studies in the intact animal have failed to demonstrate a depressant effect of verapamil on the sinus node at therapeutic doses (Garvey, 1969; Obayashi et al., 1975). Heart rate increases after iv injection of verapamil (Garvey, 1969). However, after high doses not used in the clinical setting, marked sinus suppression also ensued in the conscious dog (Obayashi et al., 1975).

Supported in part by Landesamt fur Forschung, NRW.