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钾通道开放剂克罗卡林对离体全心缺血再灌注大鼠心脏的心脏保护作用

[Cardioprotective effect of cromakalim, a K+ channel opener, on isolated globally ischemic and reperfused rat hearts].

作者信息

Taki H, Masuda Y, Yoshizumi M, Kitagawa T, Katoh I

机构信息

Department of Cardiovascular Surgery, University of Tokushima, School of Medicine, Japan.

出版信息

Nihon Kyobu Geka Gakkai Zasshi. 1993 Mar;41(3):438-44.

PMID:8478573
Abstract

Examination was made of cardioprotective effect related to the ATP-sensitive K+ (KATP) channel on isolated globally ischemic reperfused rat hearts using cromakalim, a putative ATP-sensitive K+ channel opener. The hearts were subjected to 20 min Langendorff perfusion with Krebs Henseleit Bicarbonate Buffer (KHBB) (70 cmH2O, 37 degrees C), followed by 30 min ischemia at 36 degrees C, and 30 min reperfusion with KHBB, with (cromakalim group) or without (control group) pretreatment by 10 microM cromakalim added to KHBB for 5 min prior to ischemia. Before ischemia, no significant change in heart rate (HR), left ventricular developed pressure (LVDP) or coronary flow (CF) by 10 microM cromakalim could be detected. The two groups were the same in CF during reperfusion, but recovery of HR and LVDP significantly improved in the cromakalim group. Creatine kinase (CK) leakage in the cromakalim group was significantly less than in the control group during reperfusion. Cromakalim is thus shown to reduce the myocardial injury during ischemia and reperfusion. Intracellular Ca2+ content of the cromakalim group appeared lower than that of the control group at 30 min of reperfusion. At 5-30 min of reperfusion, in the cromakalim group, intracellular Ca2+ storage was prevented, leading to a good recovery of cardiac function, while in the control group, intracellular Ca2+ increased and recovery of cardiac function was poor. After pretreatment with 10 microM cromakalim, intracellular K+ content of the cromakalim group was significantly lower than in the control group before ischemia. At 5 min of reperfusion, intracellular K+ content of the cromakalim group was slightly less than that of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

使用可能的ATP敏感性钾离子(KATP)通道开放剂克罗卡林,研究了其对离体全心缺血再灌注大鼠心脏的心脏保护作用。心脏先经Krebs-Henseleit碳酸氢盐缓冲液(KHBB)进行20分钟的Langendorff灌注(70 cmH₂O,37℃),接着在36℃下缺血30分钟,然后再用KHBB进行30分钟再灌注,缺血前5分钟,在KHBB中加入10微摩尔克罗卡林进行预处理(克罗卡林组)或不进行预处理(对照组)。缺血前,未检测到10微摩尔克罗卡林对心率(HR)、左心室舒张末压(LVDP)或冠脉流量(CF)有显著变化。再灌注期间两组的CF相同,但克罗卡林组HR和LVDP的恢复明显改善。再灌注期间,克罗卡林组的肌酸激酶(CK)漏出明显少于对照组。因此,克罗卡林可减轻缺血和再灌注期间的心肌损伤。再灌注30分钟时,克罗卡林组的细胞内Ca²⁺含量似乎低于对照组。再灌注5 - 30分钟时,克罗卡林组可防止细胞内Ca²⁺蓄积,从而使心脏功能良好恢复,而对照组细胞内Ca²⁺增加,心脏功能恢复较差。用10微摩尔克罗卡林预处理后,缺血前克罗卡林组的细胞内K⁺含量明显低于对照组。再灌注5分钟时,克罗卡林组的细胞内K⁺含量略低于对照组。(摘要截短于250字)

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