In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 20, No. 10 ( 2000-10), p. 2226-2232
Abstract:
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 (10×10 6 cells, 3 mL), platelets (400×10 6 , 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 (aMβ2, 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 H 2 O 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/cm 2 without versus 1.2±0.3/cm 2 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.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.20.10.2226
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
1494427-3
