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Ischemic Reperfusion Myocardial Injury ; Its Mechanism and Prevention.

缺血再灌注心肌损伤；

基本信息

批准号：
61570422
负责人：
KANAIDE Hideo
金额：
$ 1.47万
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 (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

The mechanism and the prevention of reperfusion myocardial injuries were investigated in the following two sets of studies:1. Mechanism of a protective effect of alloprinol(AL) on hypoxia-reoxygenation was investigated in isolated rat hearts. When AL(100 M) was added to the perfusate during prehypoxic, hypoxic and reoxy-genation periods, hearts continued to beat, though weak, during hypoxia, and tension development recover 18% of control level at 30 min of reoxygenation. Without AL, the tension development was abolished within 20 min of hypoxic perfusion, and not recovered by reoxygenation. During hypoxia, tissue ATP of AL treated hearts was much higher than that of non-treated groups. AL markedly accelerated the glycolysis during the early hypoxia. AL prevented the CPK release, reduction of Na, KATPase activity, and malondialdehyde formation during reoxygenation. Thus, in addition to the well-known inhibitory effect on oxygen radicals mediated injury, AL protects hypoxic-reoxypenated hearts by maintaining ATP at markdly high levels during hypoxia.2. The relation between Ca overload and myocardial injury in Ca-paradox was examined in naonatal rat hearts loaded with fura-2. In hearts from rats under 8 days of age, (Ca)i decreased and reached a plateau level during Ca-free perfusion, and upon Ca-repletion after 5 min, (Ca)i returned to the normal control level. Neither Ca overload nor CPK release was observed. In hearts from 9- to 14- day old rats, upon Ca-repletion, (Ca)i increased and Ca overload was observed. However, 80% of the hearts maintained contractility and there was little release of CPK. Thus, in addition to Ca overload, the maturity of sarcolemmal functions and structure is a pre-requisite for the full development of Ca-paradox injury of hearts.

通过以下两组研究探讨了再灌注心肌损伤的机制和预防措施：研究了别丙醇（AL）对离体大鼠心脏缺氧再氧化保护作用的机制。在缺氧前、缺氧和复氧期间向灌注液中加入AL(100 M)，心脏在缺氧期间继续搏动，虽然微弱，在复氧30分钟时，张力发展恢复到对照水平的18%。无AL时，低氧灌注20 min内张力发展消失，再氧不能恢复。缺氧时，AL处理组心脏组织ATP明显高于未处理组。早期缺氧时，AL明显加速糖酵解。AL阻止CPK的释放、Na的减少、KATPase活性和再氧化过程中丙二醛的形成。因此，除了众所周知的对氧自由基介导的损伤的抑制作用外，AL还通过在缺氧时将ATP维持在显著的高水平来保护缺氧再氧心脏。在载fura-2的新生大鼠心脏中研究钙超载与心肌损伤的关系。在8日龄大鼠的心脏中，（Ca）i在无Ca灌注期间下降并达到平台水平，5min后Ca充满后（Ca）i恢复到正常对照水平。没有观察到Ca超载和CPK释放。在9 ~ 14日龄大鼠心脏中，钙补充后，（Ca）i增加，出现钙超载。然而，80%的心脏保持收缩力，CPK几乎没有释放。因此，除了钙超载外，肌层功能和结构的成熟是心脏钙悖论损伤充分发展的先决条件。