| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Purpose : For successful organ transplantation, it is important to preserve the donor organ with minimum loss of function. This study was carried out to investigate the tissue damage by the activation of calpain during prolonged hypothermic cardiac preservation in isolated rat heart using specific antibodies for calpain proenzyme, and to ensure the protective effect of calpain inhibitor 1 (N-acetyl-leucyl-leucyl-norleucinal). Methods : Excised rat hearts were divided into groups : in Group I,the heart was arrested and immersed in University of Wisconsin solution with 20 mu M of calpain inhibitor 1 (n=28) and in Group N,the heart was arrested and immersed in University of Wisconsin solution without calpain inhibitor (n=27). After 12-hr preservation under ischemic conditions at 4ﾟC,the hearts were reperfused on an isolated perfusion apparatus, and the cardiac function and leaked enzyme activity were assessed. Eight hearts in each group were attended in the following study without reperfusion. Separation of the myocardial calpain isozyme was carried out by DEAE cellulose column chromatography and mu-and m-calpain proenzymes were detected by immunoblotting. Results : The cardiac function was more satisfactorily maintained in Group I than Group N.Remarkable leakage of creatine kinase, glutamic-oxaloacetic transaminase and lactate dehydrogenase was detected in Group N,while it was efficiently suppressed in Group I (p<0.01, p<0.05, and p<0.01, respectively). During ischemia, mu-calpain proenzyme was decreased in Group N (p<0.01), but there was no significant change in m-calpain. However, during reperfusion, both mu-and m-calpains were more decreased in Group N (p<0.01). Conclusion : Activation of calpain proenzymes and decrease in cardiac function during preservation and reperfusion were demonstrated. The use of calpain inhibitor to protect tissue damage was suggested to be useful for the prolonged preservation of the heart.
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