Modulation of Procainamide's Effect on Conduction by Cellular Uncoupling in Perfused Rabbit Hearts

• Published in: Journal of cardiovascular electrophysiology Vol. 8; no. 2; pp. 199 - 214
• Main Authors: SPEAR, JOSEPH F., HOOK, BRUCE G., JOSEPHSON, MARK E., NET MOORE, E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.1997
• Subjects: Action Potentials - drug effects; activation sequence maps; Alcohols - pharmacology; Animals; anisotropic conduction; Anti-Arrhythmia Agents - pharmacology; Cardiac Pacing, Artificial; Cell Communication - drug effects; Electrocardiography; Electrophysiology; Female; gap junctions; Heart Conduction System - drug effects; Heptanol; In Vitro Techniques; intracellular potentials; Male; Muscle Fibers, Skeletal - drug effects; myocardial anisotropy; Myocardium - cytology; Procainamide - pharmacology; Rabbits
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.1997.tb00781.x

Cellular Uncoupling and Procainamide's Effect. Introduction: How cell‐to‐cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell‐to‐cell electrical coupling induced by graded doses of heptanol. Methods and Results: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm × 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocar dial fiber orientation in Langendorff‐perfused rabbit hearts. The effects of procainamide (15 mg/L.) on conduction velocity were determined in the presence of increasing doses of heptanot (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated super‐refused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L, procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. Conclusions: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell‐to‐cell electrical coupling. The present model should he useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.