Ischemic Reperfusion Myocardial Injury ; Its Mechanism and Prevention.

通过以下两组研究探讨了再灌注心肌损伤的机制和预防：1。本文研究了别普利醇（AL）对离体大鼠心脏缺氧复氧的保护作用及其机制。在预缺氧、缺氧和复氧期间向灌流液中加入AL（100 M），心脏在缺氧时虽有微弱搏动，但仍能继续搏动，复氧30 min时，张力恢复到对照水平的18%。无AL时，缺氧灌注20 min内张力发展消失，复氧后不能恢复。缺氧时，AL处理组心肌组织ATP含量明显高于未处理组。AL明显促进缺氧早期糖酵解。AL可抑制再给氧过程中CPK的释放、Na，KATP酶活性的降低和丙二醛的形成。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还通过在缺氧期间维持显著高水平的ATP来保护缺氧-再氧化的心脏。在Fura-2负荷的新生大鼠心脏上，研究了钙超载与钙反常心肌损伤的关系。在8日龄以下大鼠的心脏中，在无钙灌注期间（Ca）i降低并达到平台水平，并且在5分钟后的Ca-补充时，（Ca）i恢复到正常对照水平。未观察到Ca超载或CPK释放。在9 ~ 14日龄大鼠心脏中，Ca-补充后，（Ca）i增加，观察到Ca超载。然而，80%的心脏保持收缩性，CPK释放很少。因此，除了钙超载，成熟的肌膜功能和结构是一个先决条件，充分发展的Ca-反常损伤的心脏。

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.