Davy J M, Weissenburger J, Ertzbischoff O, Lainée P, Chezalviel F, Poirier J M, Cheymol G, Motte G
Service de cardiologie, hôpital Antoine-Béclère, Clamart.
Arch Mal Coeur Vaiss. 1988 Sep;81(9):1117-24.
Sotalol is a beta-blocking agent endowed with class III electrophysiological properties. It has proved clinically effective in the treatment of arrhythmia, but episodes of torsades de pointe have been observed, particularly (though not exclusively) in the presence of hypokalaemia. The effect of sotalol with or without hypokalaemia was studied on a recently developed model for experimental torsades de pointe. Conscious dogs with complete atrioventricular block (ventricular cycle RR = 1530 +/- 170 ms) and provided with permanent atrial and ventricular epicardial electrodes were given sotalol intravenously either as a 4.5 mg/kg bolus injection or as a 1.5 mg/kg/h infusion. Group I dogs (n = 8) had normal blood potassium levels (4.3 +/- 0.1 mEq/1); following sotalol (plasma concentration 3.7 +/- 0.2 micrograms/ml) the ventricular rhythm was electrically driven to 25/min (RR = 240 ms) and QT was increased by 68 +/- 11 ms; torsades de pointe occurred in 5/8 animals (62 p. 100). Group II dogs (n = 6) had diuretic-induced hypokalaemia (2.6 +/- 0.1 mEq/1); following sotalol (plasma concentrations 3.8 +/- 0.3 micrograms/ml) the ventricular rhythm also depended on an external pacemaker to reach 25/min (in all but 1 dog) and QT increased by 46 +/- 11 ms; torsades de pointes were obtained in 5/6 animals (83 p. 100). These torsades de pointe were prevented in every case by rapid ventricular pacing (100-120/min). Thus, the pro-arrhythmic effects of sotalol were very frequent on this experimental model, but hypokalaemia was not necessary for torsades de pointe to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
索他洛尔是一种具有Ⅲ类电生理特性的β受体阻滞剂。它已被证明在治疗心律失常方面临床有效,但已观察到尖端扭转型室性心动过速发作,特别是(但不限于)在低钾血症情况下。在最近开发的实验性尖端扭转型室性心动过速模型上研究了索他洛尔在有或无低钾血症时的作用。给有意识的、完全房室传导阻滞(心室周期RR = 1530±170毫秒)并配备永久性心房和心室心外膜电极的犬静脉注射索他洛尔,剂量为4.5毫克/千克推注或1.5毫克/千克/小时输注。第一组犬(n = 8)血钾水平正常(4.3±0.1毫当量/升);给予索他洛尔后(血浆浓度3.7±0.2微克/毫升),心室节律被电驱动至25次/分钟(RR = 240毫秒),QT间期增加68±11毫秒;8只动物中有5只(62%)发生尖端扭转型室性心动过速。第二组犬(n = 6)因利尿导致低钾血症(2.6±0.1毫当量/升);给予索他洛尔后(血浆浓度3.8±0.3微克/毫升),心室节律同样依赖外部起搏器达到25次/分钟(除1只犬外所有犬),QT间期增加46±11毫秒;6只动物中有5只(83%)出现尖端扭转型室性心动过速。每次通过快速心室起搏(100 - 120次/分钟)可预防这些尖端扭转型室性心动过速。因此,索他洛尔的促心律失常作用在该实验模型中非常常见,但低钾血症并非尖端扭转型室性心动过速发生的必要条件。(摘要截断于250字)