Keller A M, Clancy R M, Barr M L, Marboe C C, Cannon P J
Department of Medicine, University College of Physicians and Surgeons.
Circ Res. 1988 Dec;63(6):1044-52. doi: 10.1161/01.res.63.6.1044.
Leukocyte-mediated myocardial reperfusion injury is characterized by the progressive migration and accumulation of polymorphonuclear leukocytes within the myocardium. In this study, we hypothesized that leukocytes normally resident to the myocardium also contribute to myocardial injury in the absence of migration and accumulation of peripheral polymorphonuclear leukocytes. In isolated crystalloid-perfused rat hearts, we found numerous resident cardiac leukocytes that were identified primarily as macrophages and mast cells, the latter staining avidly for peroxidase. When hypoxic perfused hearts (60 minutes, n = 16) were reoxygenated there was a prompt release of this peroxidase activity, the extent of which correlated closely with the degree of myocardial injury (total creatine kinase release, r = 0.96). When reoxygenation associated mast cell degranulation was prevented in six additional hypoxic hearts using 10 microM Lodoxamide Tromethamine, peroxidase release was reduced 7.8-fold (p less than 0.001) and creatine kinase release (injury) was reduced 5.9-fold (p less than 0.001). These results demonstrate that the isolated crystalloid-perfused rat heart is not a leukocyte-free preparation and suggest that mast cells resident to the heart play an important role in acute reoxygenation injury.
白细胞介导的心肌再灌注损伤的特征是多形核白细胞在心肌内进行性迁移和聚集。在本研究中，我们假设心肌中常驻的白细胞在缺乏外周多形核白细胞迁移和聚集的情况下也会导致心肌损伤。在离体晶体灌注大鼠心脏中，我们发现大量常驻心脏白细胞，主要鉴定为巨噬细胞和肥大细胞，后者对过氧化物酶染色强烈。当缺氧灌注心脏（60分钟，n = 16）复氧时，这种过氧化物酶活性迅速释放，其程度与心肌损伤程度密切相关（总肌酸激酶释放，r = 0.96）。当使用10 microM色甘酸二钠在另外6个缺氧心脏中防止复氧相关的肥大细胞脱颗粒时，过氧化物酶释放减少7.8倍（p < 0.001），肌酸激酶释放（损伤）减少5.9倍（p < 0.001）。这些结果表明，离体晶体灌注大鼠心脏并非无白细胞制剂，并提示心脏常驻肥大细胞在急性复氧损伤中起重要作用。
