Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium.
The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia-dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)
Patterson
E
E
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
Scherlag
B J
BJ
Lazzara
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D008012:Lidocaine