Electrophysiologic actions of d,l-sotalol and GLG-V-13 in ischemically injured canine epicardium.
The electrophysiologic actions of the class III antiarrhythmic agents, GLG-V-13 and d,l-sotalol, were examined in superfused normal and ischemically injured epicardium. Both drugs produced concentration and reverse-use dependent prolongation of the action potential duration in normal myocardium without altering resting potential, action potential amplitude, or Vmax. Both drugs increased the slope of restitution curves in normal epicardium but prevented action potential alternans at short cycle lengths. The response of superfused ischemically injured left ventricular epicardium to drug 4 days after coronary artery ligation was determined by the extent of ischemic injury, with no electrophysiologic changes produced within epicardial cells characterized by prominent action potential shortening and no further action potential shortening with pacing. Cells demonstrating less severe injury (as evidenced by less severely depressed action potential amplitudes, Vmax, and action potential durations) retained a limited ability to respond to drug administration with action potential prolongation. A concentration-dependent, increased disparity of action potential duration was observed concurrent with the ability of single premature stimuli to induce monomorphic tachycardia. The present data demonstrate a variable response of ischemically injured canine epicardial cells to action potential prolongation with GLG-V-13 and d,l-sotalol, facilitating localized reentry in vitro, despite a failure of the same drugs to facilitate reentrant tachycardia in vivo.
Patterson
Eugene
E
University of Oklahoma Health Sciences Center, Oklahoma State University, Stillwater, OK, USA. eugene-patterson@ouhsc.edu
Scherlag
Benjamin J
BJ
Lazzara
Ralph
R
Garrison
Gregory L
GL
Berlin
K Darrell
KD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010496:Pericardium / Q000187:drug effects; D013015:Sotalol / Q000008:administration & dosage / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; C095121:GLG-V 13; D013015:Sotalol