Differences in coupling interval‐dependent effects of sotalol on infarcted and noninfarcted areas of dog hearts after myocardial infarction

Abstract

We examined the coupling interval-dependence of the effects of sotalol (dl-sotalol) on effective refractory periods (ERPs) and epicardial activation in ventricles of dog hearts after myocardial infarction, and clarified their differences between infarcted and noninfarcted areas. Myocardial infarction was produced by the two-stage ligation of left anterior descending coronary artery in dogs. At 7 to 9 days after ligation, bipolar electrodes were sutured on the ventricular surface of the noninfarcted and the infarcted areas. Single (S1) or double (S1/S2) electrical stimulations with various coupling intervals were applied on the ventricle during atrial pacing. S1 was triggered by a prior R wave of pacing rhythm with coupling interval of 300 ms (S1[300]) or 180 ms (S1 [180]). Coupling intervals of S1 and S2 were between 250 and 130 ms. ERPs, activation delay, and functional refractory periods (FREPs) in ventricles were measured after S1(180) or S1(300). Ventricular activation delay was a time interval from the artifact of S1 or S2 to the most delayed measurable wave. The coupling interval of S1-S2 was 170 or 160 ms. RT intervals were measured in the bipolar ECGs after S1(300) or S1(180). Sotalol was administered intravenously in dosages of 2, 4, and 8 mg/kg. Sotalol prolonged the ERPs in noninfarcted areas in a lesser extent after S1(180) than after S1(300), whereas in infarcted areas the ERP prolongation was in a similar extent after S1(180) and S1(300). Sotalol prolonged the RT intervals in a lesser extent after S1(180) than after S1(300) in noninfarcted areas, but in a similar extent after S1(180) and after S1(300) in infarcted areas. FERPs were also prolonged by sotalol in infarcted areas in a similar extent after S1(180) and after S1(300). Sotalol prolonged ventricular activation delay after S1/S2 in the infarcted areas, which was greater after S1/S2(180/170) than after (300/170). Delayed activation was blocked more frequently after the S1/S2(180/ 160) than after S1/S2(300/160). These results indicate that the effects of sotalol on ventricular activation delay are reverse-use dependent in noninfarcted areas but use-dependent in infarcted areas, which may contribute to suppression of ventricular tachyarrhythmias in patients with coronary heart disease. Drug Dev. Res. 58:258-267, 2003.