CELLULAR MECHANISM UNDERLYING THE EFFICACY OF THE SOTALOL-QUINIDINE COMBINATION

被引:6
作者
BERMAN, ND
DORIAN, P
机构
[1] UNIV TORONTO,DIV CARDIOL,TORONTO M5S 1A1,ONTARIO,CANADA
[2] UNIV TORONTO,DIV CARDIOL,TORONTO M5S 1A1,ONTARIO,CANADA
[3] UNIV TORONTO,DIV CLIN PHARMACOL,TORONTO M5S 1A1,ONTARIO,CANADA
关键词
QUINIDINE; SOTALOL; SUSTAINED VENTRICULAR TACHYCARDIA; GUINEA PIG PAPILLARY MUSCLE; CONDUCTION IMPAIRMENT; ACTION POTENTIAL DURATION;
D O I
10.1097/00005344-199304000-00015
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The combination of quinidine and sotalol is very effective in prevention of recurrent sustained ventricular tachycardia (SVT). The cellular mechanisms underlying this efficacy were examined in guinea pig papillary muscle, using standard microelectrode techniques and stimulation frequencies of 1, 2, and 3 Hz. Action potential duration (APD) and effective refractory period (ERP) were measured under control conditions, after 30-min perfusion with quinindine (5 muM) or sotalol (6 muM), and after an additional 30 min of quinidine + sotalol (5 and 6 muM, respectively). Quinidine, sotalol, and quinidine + sotalol all prolonged APD at 90% repolarization (APD90) by 9 +/- 1, 13 +/- 1, and 15 +/- 2%, respectively (at 3 Hz; p = NS, comparison of the three drugs; p < 0.05 for each drug as compared with control). Quinidine + sotalol prolonged ERP (at 3 Hz) by 27 +/- 2% as compared with 11 +/- 2% after sotalol and 18 +/- 2% after quinidine alone (p < 0.05). As a result, the ERP/APD ratio was increased by the combination to 0.87 +/- 0.2 (p < 0.05) as compared with 0.78 +/- 0.2 for control 0.79 +/- 0.1 for sotalol, and 82 +/- 0.1 for quinidine (at 3 Hz). Although sotalol alone decreased the maximum rate of depolarization of phase 0 of the AP (V(max)) by only 3 +/- 2% (p = NS), sotalol attenuated V(max) decrease of quinidine (at 3 Hz) from 40 +/- 4 to 16 +/- 3% (p < 0.05). Effects at 1 and 2 Hz were similar. As compared with sotalol or quinidine alone, quinidine + sotalol markedly increased ERP without causing additional increases in APD, leading to an increased ERP/APD ratio, possibly accounting for the clinical efficacy of this combination. These changes were accompanied by less impairment of conduction than that which occurs after quinidine alone, even at a high stimulation frequency.
引用
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页码:609 / 614
页数:6
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