Electropharmacologycal therapy for lethal arrhythmias

致死性心律失常发生的电生理机制是预防心脏性猝死的药物治疗的基础。我们的小组由对心律失常和机械故障感兴趣的电药理学家组成，试图用各种方法找到治疗致命性心律失常的解决方案。Nakaya博士研究了胺碘酮对分离心肌细胞的乙酰胆碱敏感性K通道和Na激活K通道的影响，并显示了这些通道变化在动作电位延长中的作用，这对于胺碘酮治疗致死性室性心律失常的有效性很重要。Iijima博士表明，在缺血性损伤期间，NO对ATP依赖性K通道的开放具有增强作用。Kanno博士检查了延迟整流钾通道上的硫胺素衍生物。Taira博士在非洲爪蟾卵母细胞中表达了心脏K通道，并展示了这种方法在筛选K通道作用药物方面的有用性。Kodama博士表明Cl通道和肌浆Ca通道在牵张诱导的心动过速中的作用，这也可能在心室兴奋性中起作用。Nishi博士还显示了Cl通道阻滞剂可能的抗肿瘤作用。Endoh、Tsujimoto、Kimura和Hashimoto博士提出了Na/Ca交换或Na/H交换α_1受体抑制剂可能的抗肿瘤作用。在用Na、K、Ca通道阻滞剂治疗心脏性猝死的临床效果不佳的时代，我们的研究结果显示了药物调节心脏通道、受体和α交换剂治疗致死性心律失常的可能性。

Electrophysiological mechanisms of generation of lethal arrhythmias are the basis of the pharmacological treatment of the prevention of cardiac sudden deaths. Our group consisted of electropharmacologists interests in cardiac arrhythmias and mechanical failure tried to find solutions to treat lethal arrhythmias using variousmethods. Dr.Nakaya studied effects of amiodarone on the acetylcholine sensitive K channels and Naactivated K channels of isolated cardiac myocytes and showed a role of these channel changes in the action petential prolongation, which is important for amiodarone's effectiveness on lethal ventricular arrhythmias. Dr.Iijima showed potentiating effect of NO on the opening of ATP dependent K channels during ischemic insults. Dr.Kanno examined thiamine derivatives on the delayd rectifier K channels. Dr.Taira expressed cardiac K channels in Xenopus oocytes and showed the usefulness of this method to screen K channel acting drugs. Dr.Kodama showed a role of Cl channels and sarcoplasmic Ca channels in the stretch induced tachycardia, which may also play a role in the ventricular excitability. Dr.Nishi also showed a possible antiarrhythmic effect of Cl channel blockers. Dr.Endoh, Tsujimoto, Kimura and Hashimoto proposed possible antiarrhythmic effects of inhibitors of Na/Ca exchange or Na/H exchage, alpha_1 receptors. In the era of negative clinical results of using Na, K andCa channel blockers to treat sudden cardiac deaths, our results showed possibilities of pharmacological modulations of cardiac channels, receptors and alpha exchagers on treating lethal arrhythmias.