Tang L D, Tang Z M
Department of Pharmacology, Academy of Military Medical Sciences, Beijing, China.
Yao Xue Xue Bao. 1991;26(2):91-5.
Protective effects of cysteine (Cys), N-acetylcysteine (NAC), cysteamine (MEA), cystamine (CSSC) and aminopropylmethylisothiourea (APMT) on ischemia/reperfusion induced arrhythmias were studied in isolated Langendorff perfused rat hearts. The arrhythmias were caused by ligation of the anterior descending branch of the left coronary artery for 10 min and reperfused for 5 min. The drugs were dissolved in saline (NS) and perfused through a peristaltic pump system at 0.1, 0.6 or 3.6 mumol/min (n = 10), starting from 10 min before ligation up to 5 min after reperfusion. The control hearts were perfused with NS. The results showed that Cys, NAC and MEA pursued at 0.6-3.6 mumol/min significantly reduced the incidence of ventricular fibrillation (VF), which were 80-90% in control and 0-20% in 3 treated groups, with P less than 0.01-0.001. The duration of ventricular tachycardia (VT) + VF was 3.0 +/- 1.6 min in control and were 0.2 +/- 0.2, 0.2 +/- 0.1 and 1.2 +/- 2.1 min in Cys, NAC and MEA groups, respectively (with P less than 0.01-0.001). Coronary flow (CF) were remarkably reduced to about 50% during ligation in NS, but remained at normal levels in three treated groups. There were no significant protective effects on arrhythmias in CSSC and APMT perfused hearts. CF of CSSC and APMT groups were even less than those of control. The structure-activity analysis suggested that the SH group may play a crucial role in the protective effect of SH compounds on ischemia/reperfusion induced arrhythmias. The mechanism of protection was briefly discussed in this paper.
在离体Langendorff灌注大鼠心脏中研究了半胱氨酸(Cys)、N-乙酰半胱氨酸(NAC)、半胱胺(MEA)、胱胺(CSSC)和氨丙基甲基异硫脲(APMT)对缺血/再灌注诱导的心律失常的保护作用。心律失常通过结扎左冠状动脉前降支10分钟并再灌注5分钟诱导产生。将药物溶解于生理盐水(NS)中,通过蠕动泵系统以0.1、0.6或3.6 μmol/分钟的速度灌注(n = 10),从结扎前10分钟开始直至再灌注后5分钟。对照心脏用NS灌注。结果显示,以0.6 - 3.6 μmol/分钟灌注的Cys、NAC和MEA显著降低了室颤(VF)的发生率,对照组中VF发生率为80 - 90%,三个治疗组中为0 - 20%,P < 0.01 - 0.001。对照组室性心动过速(VT) + VF的持续时间为3.0 ± 1.6分钟,Cys、NAC和MEA组分别为0.2 ± 0.2、0.2 ± 0.1和1.2 ± 2.1分钟(P < 0.01 - 0.001)。在NS灌注组中,结扎期间冠状动脉血流量(CF)显著降低至约50%,但在三个治疗组中保持在正常水平。CSSC和APMT灌注的心脏对心律失常无显著保护作用。CSSC和APMT组的CF甚至低于对照组。构效关系分析表明,SH基团可能在含SH化合物对缺血/再灌注诱导的心律失常的保护作用中起关键作用。本文简要讨论了保护机制。