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PREVENTION OF ISCHEMIA-REPERFUSION INJURY AND ESTABLISHMENT OF THE METHODS FOR CARDIAC PRESERVATION AND REPERFUSION

缺血再灌注损伤的预防和心脏保护和再灌注方法的建立

基本信息

批准号：
03454334
负责人：
KOHNO Hiroyuki
金额：
$ 4.1万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

1. To prevent intracellular calcium overload, we investigated the hyperpolarizing cardioplegia which we had made in 1991. The hyperpolirizing cardioplegia consists of low potassium and contains adenosine and pinacidil (potassium channel opener). As it keeps cell membrane hyperpolirizing, we assume that L-type calcium channels on cardiac myocyte is kept close and that intracellular calcium overload was prevented. We compared the protective effect of the hyperpolarizing cardioplegia with that of ordinary high potassium cardioplegia in isolated rat heart model. The protective effect of hyperpolarizing cardioplegia was similar to that of the high potassium cardioplegia.2. We investigated the effects of cardioplegia containing angiotensin converting enzyme (ACE) inhibitor on ischemia/reperfusion in rat hearts. The cardioplegia contaning 2.5mmole/L captopril showed good myocardial protection during reperfusion but not during ischemia. Another ACE inhibitor, Enalapril and Lisinopril showed no effect during neither ischemia nor reperfusion. Because only captopril has a sulfhydryl, we considered myocardial protective effect of captopril might be due to free radical scavenging rather than ACE inhibition.3. We planed to measure intracellular calcium concentration and intracellular pH during ischemia and reperfusion in isolated cardiac myocytes. We succeeded to get enough myocytes from ventricular muscle of rat for experiments to measure both intracellular calcium concentration and pH by loading of Fura-2 and BCECF. Because we have not yet succeeded to keep isolated myocyte in ischemia, we cannot report fully about this experiment.4. Now, we are making a new experimental model in which we measure intracellular calcium concentration and pH in isolated rat of rabbit heart at global ischemia. When we establish this model, it might be one of the best model to examine calcium homeostasis during ischemia and reperfusion.

1.为防止心肌细胞内钙超载，我们于1991年研制了超极化停搏液。高极化心脏停搏液由低钾组成，并含有腺苷和吡那地尔（钾通道开放剂）。由于它保持细胞膜的高度极化，我们假设心肌细胞上的L-型钙通道保持关闭，从而防止细胞内钙超载。在离体大鼠心脏模型上，比较了超极化停搏液与普通高钾停搏液的保护作用。超极化停搏液对心肌的保护作用与高钾停搏液相似.本文观察了含血管紧张素转换酶（ACE）抑制剂的停搏液对大鼠心脏缺血再灌注的影响。含2.5mmol/L卡托普利的停搏液对再灌注心肌有较好的保护作用，但对缺血心肌无明显保护作用。另一种ACE抑制剂依那普利和赖诺普利在缺血和再灌注期间均无作用。由于卡托普利中只有一个巯基，我们认为其心肌保护作用可能是通过清除自由基而不是抑制ACE.我们计划在离体心肌细胞缺血和再灌注期间测量细胞内钙浓度和细胞内pH。通过Fura-2和BCECF的负载，我们成功地从大鼠心室肌中获得了足够的心肌细胞，用于测量细胞内钙浓度和pH的实验。由于我们还没有成功地将离体心肌细胞保持在缺血状态，因此我们不能对本实验进行全面报道。本实验建立了一种新的离体兔心缺血模型，测定了全脑缺血时心肌细胞内钙离子浓度和pH值。该模型的建立可能是研究缺血再灌注钙稳态的最佳模型之一。