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)