Electropharmacologycal therapy for lethal arrhythmias

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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.