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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2226.)
© 2000 American Heart Association, Inc.

Vascular Biology

c7E3Fab Reduces Postischemic Leukocyte-Thrombocyte Interaction Mediated by Fibrinogen

Implications for Myocardial Reperfusion Injury

Christian Kupatt; Helmut Habazettl; Peter Hanusch; Reinhard Wichels; Daniela Hahnel; Bernhard F. Becker; Peter Boekstegers

From Internal Medicine I (C.K., P.H., R.W., D.H., P.B.), Klinikum Grosshadern, the Institute for Surgical Research (H.H.), and the Department of Physiology (B.F.B.), Ludwig-Maximilians-University of Munich, Munich, Germany.

Correspondence to Christian Kupatt, MD, Internal Medicine I, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany. E-mail c.kupatt{at}lrz.uni-muenchen.de

Abstract—Reperfusion injury after coronary occlusion is in part mediated by leukocyte activation and adhesion. Platelets may interact with polymorphonuclear granulocytes (PMNs), causing aggravated reperfusion injury. We studied whether c7E3Fab, a chimeric Fab fragment blocking platelet glycoprotein (GP) IIb/IIIa, decreases PMN-platelet–dependent myocardial dysfunction after ischemia. Isolated guinea pig hearts (n=5 per group) perfused at a constant flow of 5 mL/min were subjected to ischemia (15 minutes, 37°C) and reperfusion. Human PMNs (10x10⁶ cells, 3 mL), platelets (400x10⁶, 3 mL), and fibrinogen (1 mg/mL) were infused for 3 minutes after 2 minutes of reperfusion, with or without c7E3Fab. Flow cytometry detected GPIIb/IIIa (platelets) and MAC-1 (aMß2, PMNs) as well as coaggregates of both in the effluent, whereas double-fluorescence microscopy visualized intracoronary PMN-platelet coaggregates. Postischemic recovery of pressure-volume work (12–cm H₂O preload and 60–mm Hg afterload) was defined as the ratio of postischemic to preischemic external heart work (mean±SEM). c7E3Fab reduced platelet GPIIb/IIIa detection to 10% of controls, blocked a transcoronary MAC-1 increase (+25% without versus -23% with c7E3Fab), and inhibited PMN-platelet coaggregation in the effluent (49±12% without versus 17±2% with c7E3Fab) as well as in the hearts themselves (5.0±0.7/cm² without versus 1.2±0.3/cm² surface area with c7E3Fab). Postischemic recovery of external heart work (83±5% in cell-free hearts) declined to 46±4% after postischemic PMN-platelet infusion, but not in the presence of c7E3Fab (74±11%) or LPM19c (71±6%). We conclude that c7E3Fab inhibits formation of PMN-platelet aggregates during myocardial reperfusion, an effect that protects against PMN-platelet–dependent stunning.

Key Words: abciximab • polymorphonuclear neutrophils • platelets • myocardial stunning • microcirculation • fibrinogen

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