Yamashita N, Hoshida S, Taniguchi N, Kuzuya T, Hori M
First Department of Medicine, Osaka University Medical School, Japan.
J Mol Cell Cardiol. 1998 Jun;30(6):1181-9. doi: 10.1006/jmcc.1998.0682.
We and others found that cardioprotection is acquired not only soon after, but also 24 h after ischemic preconditioning in canine and rabbit myocardial infarction models (second window of protection). However, a second window phenomenon against myocardial infarction was dependent on species limitations and has not been observed in porcine hearts. In this study, we examined whether the "second window of protection" against myocardial infarction is observed in the rat heart. In the ischemic preconditioning (IP) group, the left main coronary artery (LCA) of rats was occluded four times for 3 min. each separated by reperfusion for 10 min. After 0, 3, and 24 h, the rats were subjected to a 20-min LCA occlusion followed by 48-h reperfusion. At 0 and 24 h after IP, infarct size and the incidence of ventricular fibrillation (VF) during ischemia were significantly reduced compared with corresponding sham-operated groups without preconditioning. After 3 h of IP, there were no differences either in the incidence of VF during ischemia or in infarct size. Manganese superoxide dismutase (Mn-SOD) content in ischemic (LCA) region of myocardium significantly increased as compared with that of sham-operated rats 24 h after IP. Treatment with N-2-mercaptopropionyl glycine, an antioxidant and a hydroxyl radical scavenger, during IP abolished the early-phase (0 h after IP) and late-phase (24 h after IP) cardioprotection and the corresponding late increase in Mn-SOD content. These results indicate that a "second window of protection" against myocardial infarction also exists in rat hearts and the induction of an intrinsic scavenger, Mn-SOD, via free radical production during IP may be important in the second window of protection.
我们和其他研究人员发现，在犬类和兔类心肌梗死模型中，心肌保护不仅在缺血预处理后很快获得，而且在24小时后也能获得（保护的第二窗口）。然而，针对心肌梗死的第二窗口现象取决于物种限制，在猪心脏中尚未观察到。在本研究中，我们研究了在大鼠心脏中是否能观察到针对心肌梗死的“保护第二窗口”。在缺血预处理（IP）组中，大鼠的左冠状动脉（LCA）被阻断4次，每次3分钟，每次阻断后再灌注10分钟。在0、3和24小时后，对大鼠进行20分钟的LCA阻断，随后再灌注48小时。与未进行预处理的相应假手术组相比，IP后0小时和24小时，梗死面积和缺血期间室颤（VF）的发生率显著降低。IP 3小时后，缺血期间VF的发生率和梗死面积均无差异。与假手术大鼠相比，IP 24小时后，心肌缺血（LCA）区域的锰超氧化物歧化酶（Mn-SOD）含量显著增加。在IP期间用抗氧化剂和羟基自由基清除剂N-2-巯基丙酰甘氨酸治疗，消除了早期（IP后0小时）和晚期（IP后24小时）的心脏保护作用以及相应的Mn-SOD含量的后期增加。这些结果表明，大鼠心脏中也存在针对心肌梗死的“保护第二窗口”，并且在IP期间通过自由基产生诱导内源性清除剂Mn-SOD可能在保护的第二窗口中起重要作用。
