致死性不整脈の成立機序

致死性心律失常的机制

• 批准号: 06304030
• 负责人: TOYAMA Junji
• 金额: $ 2.18万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06304030/
• 关键词: re-entry of excitation; ischemia and K^+ accumulation; inhomogeneous excitability; modulation of ventricular repolarization; 致死性不整脈; 心室細動; 興奮伝導異方向性; Kチャネルブロッカー; 電気ショック; 細胞間結合

This study was aimed to investigate the mechanisms of life-threatening ventricular tachyarrhythmias complicated with the acute and chronic phase of ischemia, and to find clues to develop pharmacologic and non-pharmacologic treatments for such arrhythmias.In acute ischemia, potassium ion (K^+) was released from ATP-depleted myocytes by opening the ATP-dependent potassium channel and inhibition of Na-K pump, and was thus accumulated in the extracellular space. Such K^+ accumulation was not homogeneous but dependent on the severity of the ischemia, thereby leading to re-entrant arrhythmias caused by inhomogeneous depression of excitability and conductivity in the ischmic region. Administration of Mg ion or potassium channel opener could prevent such ventricular arrhythmias experimentally, but a further study should be done before clinical application.In the chronic phase of ischemia, inhomogeneities of excitiation couduction were developed through remodelings of failing heart such as healing and/or apoptotic processes of muscle fibers in association with reactive proliferation of connective fibers. Thus, such complicated processes and reactions of the cardiac tissue shoud be taken into account in order to develop new pharmacological and non-pharmacological treatments for ventricular arrhythmias in the chronic phase of ischemia.

本研究旨在探讨急性和慢性缺血时出现的危及生命的室性快速心律失常的机制，并为此类心律失常的药物和非药物治疗提供线索。并因此在细胞外空间中积累。这种K^+的积累并不是均匀的，而是依赖于缺血的严重程度，从而导致缺血区域兴奋性和传导性的不均匀抑制引起折返性心律失常。在缺血慢性期，心肌细胞兴奋传导的不均匀性是通过衰竭心脏的重塑，如肌纤维的愈合和/或凋亡过程，以及结缔组织的反应性增生而形成的。因此，为了开发新的治疗缺血慢性期室性心律失常的药物和非药物治疗方法，应考虑心脏组织的这种复杂过程和反应。

项目成果

Ebato M,Tsunakawa H,Kobayashi T,Nakayama M,Mashima S: "Effects of early coronary reperfusion on the time course of signal-averaged electrocardiogram after myocardial infarction and its relation to late arrhythmic events." Jpn Circ J. 59. 264-273 (1995)

Ebato M、Tsunakawa H、Kobayashi T、Nakayama M、Mashima S：“早期冠状动脉再灌注对心肌梗死后信号平均心电图时程的影响及其与晚期心律失常事件的关系。”

Arai A, Kodama I, Toyama J: "Roles of Cl-channels and Ca2+ mobilization in the stretchinduced increase of SA node pacemaker activity." Am J Physiol. (in press). (1995)

Arai A、Kodama I、Toyama J：“Cl 通道和 Ca2 动员在拉伸诱导的 SA 节点起搏器活动增加中的作用。”

Taniguchi A,Toyama J,Kodama I,Anno T,Shirakawa M,Usui S: "Inhomogeneity of cellular activation time and Vmax in normal myocardial tissue under electrical field stimulation." Am J Physiol. 267. H696-705 (1994)

Taniguchi A、Toyama J、Kodama I、Anno T、Shirakawa M、Usui S：“电场刺激下正常心肌组织中细胞激活时间和 Vmax 的不均匀性。”

TOYAMA Junji: "Ca2_<+->calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig heart." Journal of Molecular and Cellular Cardiology. 26. 1007-1015 (1994)

TOYAMA Junji：“Ca2_<->钙调蛋白介导的从豚鼠心脏分离的心室肌细胞电耦合的调节。”

笠間正文: "代謝抑制後の心筋活動電位持続時間の一過性延長について" Jpn J Electrocardiol. 14. 242-252 (1994)

Masafumi Kasama：“代谢抑制后心肌动作电位持续时间的短暂延长”Jpn J Electrocardiol。14. 242-252 (1994)