© 1974 American Heart Association, Inc.
Effect of Verapamil on the Sinoatrial and Atrioventricular Nodes of the Rabbit and the Mechanism by Which it Arrests Reentrant Atrioventricular Nodal Tachycardia
1 The Rockefeller University, New York, New York 10021
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 Words: slow response • calcium-dependent action potentials • cardiac antiarrhythmic drugs • reentrant arrhythmias • tachycardia • overshoot • effective refractory period
Accepted on May 24, 1974
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