Nicolini F A, Mehta J L, Nichols W W, Donnelly W H, Luostarinen R, Saldeen T G
Department of Medicine, University of Florida, College of Medicine, Gainesville.
Am Heart J. 1991 Nov;122(5):1245-51. doi: 10.1016/0002-8703(91)90562-v.
Leukocyte-derived elastase is released following coronary artery occlusion and reperfusion and may contribute to reperfusion-related myocardial injury. Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury.
白细胞衍生的弹性蛋白酶在冠状动脉闭塞和再灌注后释放，可能导致与再灌注相关的心肌损伤。白细胞浸润到再灌注的心肌中也可能导致再灌注后的缺血性损伤。在本研究中，我们在电诱导冠状动脉血栓形成的犬中，研究了静脉注射组织型纤溶酶原激活剂（t-PA，20分钟内1mg/kg）联合生理盐水或白细胞弹性蛋白酶抑制剂（ICI 200,880，5mg/kg）的效果。给予ICI 200,880可增加弹性蛋白酶抑制活性，而不影响t-PA和纤溶酶原激活剂抑制剂（PAI-1）的活性。给予t-PA联合生理盐水或弹性蛋白酶抑制剂的犬，其再灌注时间、冠状动脉血流峰值幅度和再灌注持续时间并无差异。然而，给予弹性蛋白酶抑制剂可减少经组织学确定的白细胞浸润以及冠状动脉血栓形成和随后溶栓的犬的心肌损伤严重程度。这些早期观察结果表明，再灌注期间弹性蛋白酶的释放可能是缺氧-复氧介导的组织损伤的重要介质。
