Elsevier

American Heart Journal

Volume 122, Issue 5, November 1991, Pages 1245-1251
American Heart Journal

Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: Beneficial effects on myocardial histology

https://doi.org/10.1016/0002-8703(91)90562-VGet rights and content

Abstract

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.

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Supported by a Veterans Administration Merit Review and by Clinical Investigator Awards (J. L. M.); by an American Heart Association Research Fellowship (F. A. N.); and by the Swedish Medical Research Council.

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