Electropharmacologycal therapy for lethal arrhythmias

致死性心律失常发生的电生理机制是预防心源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学家组成，试图用各种方法寻找治疗致命性心律失常的解决方案。Nakaya博士研究了胺碘酮对心肌细胞乙酰胆碱敏感钾通道和钠激活钾通道的影响，并证明了这些通道的改变在动作电位延长中的作用，这对胺碘酮治疗致死性室性心律失常的效果是重要的。Iijima博士发现，在缺血损伤过程中，NO对依赖于ATP的K通道的开放有增强作用。菅野博士检查了延迟整流K通道上的硫胺素衍生物。Taira博士在非洲爪哇卵母细胞中表达了心脏K通道，并证明了该方法在筛选K通道作用药物方面的有效性。在牵张诱发的心动过速中，小玉博士证实了氯通道和肌浆钙通道的作用，这也可能在室性心动过速中起作用。Nishi博士还展示了氯通道阻滞剂可能的抗心律失常作用。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心律失常作用。在使用钠、钾和钙通道阻滞剂治疗心脏性猝死的临床结果为阴性的时代，我们的结果表明，心脏通道、受体和α交换器的药理调节在治疗致死性心律失常方面是可能的。

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.