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。为了防止细胞内钙超负荷，我们研究了我们在1991年制造的超极化心脏病。过度透明的心脏杂志由低钾组成，并含有腺苷和腺苷（钾通道开瓶器）。由于它保持细胞膜过度溶质化，因此我们假设心肌细胞上的L型钙通道保持近距离，并且可以防止细胞内钙过载。我们比较了超极化心脏的保护作用与分离的大鼠心脏模型中普通高钾心脏的保护作用。超极化心脏的保护作用类似于高钾心脏杂志的保护作用。2。我们研究了含有血管紧张素转化酶（ACE）抑制剂对大鼠心脏缺血/再灌注的影响。心脏杂草脉的2.5mmole/l卡托普利在再灌注过程中表现出良好的心肌保护，但在缺血期间没有表现出良好的心肌保护。另一种ACE抑制剂，依那普利和丽索普利在缺血和再灌注期间均未表现出任何作用。由于只有卡托普利具有硫酰亚胺素，因此我们认为卡托普利的心肌保护作用可能是由于自由基的清除而不是ACE抑制作用。3。我们计划在缺血期间测量细胞内钙浓度和细胞内pH，并在分离的心肌细胞中再灌注。我们成功地从大鼠的心室肌肉中获得足够的肌细胞进行实验，以通过Fura-2和BCECF的负载来测量细胞内钙浓度和pH值。因为我们尚未成功地保持缺血中孤立的肌细胞，所以我们无法充分报告有关此实验的4。现在，我们正在制作一个新的实验模型，其中我们在全球缺血的兔心脏分离的大鼠中测量细胞内钙浓度和pH值。当我们建立此模型时，它可能是检查缺血和再灌注期间钙稳态的最佳模型之一。