Effect of Verapamil on the Sinoatrial and Atrioventricular Nodes of the Rabbit and the Mechanism by Which it Arrests Reentrant Atrioventricular Nodal Tachycardia

Abstract

The effects of verapamil, an antiarrhythmic drug that apparently blocks slow inward currents, were studied on the isolated, superfused sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart with intracellular microelectrodes. Verapamil decreased the rate of spontaneous impulse initiation by the SA node. This effect could be overcome with epinephrine. Concomitantly, verapamil decreased the amplitude of SA node action potentials without reducing maximum diastolic potential. The peak of the action potential fell well short of reversal after exposure to the drug. Verapamil had similar effects on the action potentials of the upper and middle AV nodal regions, reducing action potential amplitude so that the overshoot vanished without significantly reducing maximum diastolic potential. Action potentials of fibers in the lower region of the AV node were not affected as greatly. Verapamil slowed conduction of atrial impulses through the AV node; such slowing increased when the atrial rate increased. Verapamil also prolonged the effective refractory period of the AV node, thus slowing or blocking conduction of premature impulses. Verapamil prevented AV nodal reentry and initiation of atrial tachycardia by causing premature impulses to block rather than to conduct with the delay needed to initiate reentry. Verapamil had no effect on the rate of depolarization, action potential amplitude, or maximum diastolic potential of atrial or His bundle fibers. The results are consistent with the hypotheses that fibers in the SA and AV nodes show slow response activity, that the slow response plays a crucial role in causing certain cardiac arrhythmias, and that drugs that block the slow response are therefore antiarrhythmic. KEY WORDSslow response cardiac antiarrhythmic drugs tachycardia overshoot calcium-dependent action potentials reentrant arrhythmias effective refractory period

Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle

“…These parameters, in sino-atrial node are known to depend on the slow inward current carried by Ca and/ or Na (Noble, 1984) and inhibited by calcium antagonists. Our results show that the effects of diclofurime on the AP of sinus node are similar to those of verapamil (Wit & Cranefield, 1974;Gautier & Guiraudou, 1978), diltiazem and nifedipine (Kawai et al, 1981). Our voltage clamp study on frog atrial fibres also shows that diclofurime decreases the slow inward current.…”

Electromechanical effects of bepridil on rabbit isolated hearts

“…In this respect, bepridil seems similar to these drugs. However, with verapamil and D-600, the threshold concentration for the development of fast channel inhibition are 20 to 100 times higher than those for slow channel inhibition (Rosen et al, 1974;Wit & Cranefield, 1974;Bayer et al, 1975;Hirata etal., 1979). Therefore, the former effect is considered to be negligible within the therapeutic concentration range (Singh & Mandel, 1980).…”

Increased dependency of cardiac pacemaker activity on extracellular Ca after adrenergic blockade in the frog heart.

“…Not only Ca entry blockers but also decreases in the extracellular Cat + concentration ([Ca2 +]e) are able to effectively suppress pacemaker action potentials of the heart (BROOKS and Lu,1972;KOHLHARDT and FLECKENSTEIN, 1976;SEIFEN et al, 1964;WIT and CRANEFIELD, 1974). In the frog heart, however, superfusing the sinus venosus with a Ca2+-free solution failed to arrest the regular pacemaker activity (FUKUDA, 1984).…”