Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.
BACKGROUND
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.


RESULTS
Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial 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 heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused 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 be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.
Spear
J F
JF
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA.
Hook
B G
BG
Josephson
M E
ME
Moore
E N
EN
D000200:Action Potentials / Q000187:drug effects; D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D002450:Cell Communication / Q000187:drug effects*; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D019850:Heptanol; D066298:In Vitro Techniques; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D011342:Procainamide / Q000494:pharmacology*; D011817:Rabbits
D000438:Alcohols; D000889:Anti-Arrhythmia Agents; D019850:Heptanol; D011342:Procainamide