Electrophysiological effects of MS-551, a new class III agent: comparison with dl-sotalol in dogs.
Electrophysiological effects of MS-551, a new class III agent: comparison with dl-sotalol in dogs.
复制标题
MS-551（一种新的 III 类药物）的电生理效应：与狗体内的 dl-索他洛尔比较。
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
B. Singh
中科院分区：
文献类型：
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作者：
L. Sen;G. Cui;Y. Sakaguchi;B. Singh
MS-551是一种新合成的非特异性钾通道阻滞剂。为了阐明其相对于dl-索他洛尔在体内的电生理学和潜在的预防作用，在戊巴比妥麻醉开胸犬中同时测量了ECG、心内膜和心外膜单相动作电位持续时间以及左心室和右心室压力的系列变化。房室结内注射37%甲醛造成完全性心脏传导阻滞。MS-551静脉给药在输注开始后立即导致90%复极时间（APD 90）时的动作电位时程延长，并在10 min时达到平台期。MS-551（1 mg/kg）在700 msec的基础周期长度下导致APD 90增加73 +/- 8%，QTc增加28 +/- 5%。1 mg/kg MS-551诱导的APD_（90）最大延长量比同剂量索他洛尔增加39%（P <0.01）。MS-551延长心室有效不应期的量效曲线较索他洛尔明显左移。MS-551和索他洛尔的EC 50分别为0.5 +/- 0.1 mg/kg和1.2 +/- 0.2 mg/kg（P <0.05）。当使用0.5 mg/kg MS-551剂量时，在200 msec基本周期长度下刺激未诱导室性心律失常。当给予1.5 mg/kg索他洛尔时，5/15例发生尖端扭转型室速，2/15例发生室颤，5/15例发生持续性室性心动过速。索他洛尔可显著降低自主心室率和左心室压力，而MS-551则无此作用。总之，MS-551是一种有效的III类抗心律失常药，可选择性地抑制心室肌复极，似乎没有自主神经效应。在犬心脏传导阻滞模型中，剂量与剂量相比，它在延长APD 90和右心室有效不应期方面更有效，可能具有较低的致心律失常倾向。
MS-551 is a newly synthesized, nonspecific K+ channel blocker. To elucidate its electrophysiological and potential proarrhythmic effects relative to those of dl-sotalol in vivo, serial changes in ECGs, endocardial and epicardial monophasic action potential durations, and left and right ventricular pressures were measured simultaneously in pentobarbital-anesthetized open-chest dogs. Complete heart block was produced by the injection of 37% formaldehyde into the atrioventricular node. Intravenous administration of MS-551 produced prolongation of action potential duration at 90% repolarization time (APD90) immediately after the beginning of infusion and reached plateau at 10 min. MS-551 (1 mg/kg) caused 73 +/- 8% increase in APD90 and 28 +/- 5% increase in QTc at basic cycle length of 700 msec. The maximal prolongation of APD90 induced by 1 mg/kg MS-551 was 39% greater than that by the same dose of sotalol (P < .01). The dose-response curve of prolongation of ventricular effective refractory period produced by MS-551 was shifted significantly to the left compared with that induced by sotalol. The EC50 was 0.5 +/- 0.1 mg/kg and 1.2 +/- 0.2 mg/kg for MS-551 and sotalol, respectively (P < .05). When 0.5 mg/kg MS-551 doses were used, no ventricular arrhythmia was induced by stimulation at 200-msec basic cycle length. When 1.5 mg/kg sotalol was administered, 5 of 15 developed torsade de pointes, 2 of 15 developed ventricular fibrillation and 5 of 15 developed sustained ventricular tachycardia. The idioventricular rates and left ventricular pressures were reduced significantly by sotalol, not by MS-551. In conclusion, MS-551 is a potent class III antiarrhythmic agent that selectively prolongs repolarization in the ventricular myocardium and appears to be devoid of autonomic effects. Dose for dose, it is more potent in prolonging the APD90 and the right ventricular effective refractory period possibly with a lower tendency for the development of proarrhythmia in a canine heart-block model.
dl-索他洛尔的 β-肾上腺素能阻滞特性在异丙肾上腺素治疗后对豚鼠心室肌维持 III 级功效。
影响因子：
37.8
作者：
Groh,WJ;Gibson,KJ;McAnulty,JH;Maylie,JG
通讯作者：
Maylie,JG