Galcia-Alves M, Kadowaki Y, Iwashita Y, Nishi K
Department of Pharmacology, Kumamoto University Medical School, Japan.
Jpn J Pharmacol. 1989 Oct;51(2):199-209. doi: 10.1254/jjp.51.199.
Effects of a newly introduced polyoxyethylene-modified superoxide dismutase (SOD-POE) on reperfusion induced arrhythmias were examined in the pentobarbital anesthetized rat. Reperfusion induced arrhythmias were elicited by occlusion of the left anterior descending coronary artery (LAD) for 15 min and subsequent release. The LAD occlusion was performed by compressing the artery using a suction cup of 2 mm in diameter placed on the LAD to which negative pressure was applied. The LAD occlusion and release was repeated at an interval of 30 min. SOD-POE or human SOD (h-SOD) (1000 U/kg) was injected intravenously 15 min prior to the occlusion at the second trial of the occlusion. In the control group, various types of arrhythmias including ventricular fibrillation (Vf), ventricular tachycardia (VT), premature ventricular contraction (PVC) and premature atrial contraction (PAC) were elicited immediately after release of the occlusion. In the SOD-POE-treated group, Vf and VT were completely prevented and the numbers of PVC and PAC significantly decreased, while pretreatment with h-SOD did not prevent the occurrence of reperfusion induced arrhythmias. The protective effects of SOD-POE lasted for more than 90-120 min. The plasma half life for SOD-POE was 10.8 hr, while that for h-SOD was 8.6 min. Results indicate that intravenous administration of SOD-POE would provide a new means of preventing reperfusion induced arrhythmias occurring in clinical situations.
在戊巴比妥麻醉的大鼠中,研究了新引入的聚氧乙烯修饰超氧化物歧化酶(SOD-POE)对再灌注诱导的心律失常的影响。通过闭塞左冠状动脉前降支(LAD)15分钟并随后松开引发再灌注诱导的心律失常。使用放置在LAD上的直径为2mm的吸盘施加负压来压迫动脉,从而进行LAD闭塞。LAD闭塞和松开以30分钟的间隔重复进行。在第二次闭塞试验中,在闭塞前15分钟静脉注射SOD-POE或人超氧化物歧化酶(h-SOD)(1000U/kg)。在对照组中,闭塞松开后立即引发包括心室颤动(Vf)、室性心动过速(VT)、室性早搏(PVC)和房性早搏(PAC)在内的各种类型的心律失常。在SOD-POE治疗组中,Vf和VT完全得到预防,PVC和PAC的数量显著减少,而用h-SOD预处理未能预防再灌注诱导的心律失常的发生。SOD-POE的保护作用持续超过90-120分钟。SOD-POE的血浆半衰期为10.8小时,而h-SOD的血浆半衰期为8.6分钟。结果表明,静脉注射SOD-POE将为预防临床情况下发生的再灌注诱导的心律失常提供一种新方法。