| Research Abstract |
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.
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