Ischemic Reperfusion Myocardial Injury ; Its Mechanism and Prevention.

主要研究内容如下：1.在大鼠离体心模型上，研究了别丙素醇(AL)对缺氧-复氧的保护作用机制。当在低氧前、低氧和复氧期间向灌流液中加入AL(100M)时，心脏在低氧期间继续跳动，尽管很弱，但在复氧30分钟时，张力发展恢复到对照水平的18%。在无AL的情况下，低氧灌流后20min内血压发展完全消失，复氧后不能恢复。低氧时，AL处理组大鼠心脏组织中的ATP含量明显高于未处理组。在低氧早期，铝显著促进糖酵解。Al可抑制复氧过程中CPK的释放、Na、KATPase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还通过在低氧期间保持显著的高水平的ATP来保护缺氧再氧损伤的心脏。在Fura-2负荷的新生大鼠心脏上，研究了钙悖论中钙超载与心肌损伤的关系。8日龄以下大鼠心脏无钙灌流时，(Ca)i下降并达到平台期水平，5min后恢复至正常对照水平。未观察到钙超载和CPK释放。在9日龄至14日龄大鼠心脏中，缺钙时，(Ca)i升高，并出现钙超载现象。然而，80%的心脏保持了收缩能力，CPK几乎没有释放。因此，除钙超载外，心肌细胞膜功能和结构的成熟是心肌钙悖论损伤充分发展的先决条件。

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.