c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated byfibrinogen - Implications for myocardial reperfusion injury

Citation
C. Kupatt et al., c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated byfibrinogen - Implications for myocardial reperfusion injury, ART THROM V, 20(10), 2000, pp. 2226-2232
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
20
Issue
10
Year of publication
2000
Pages
2226 - 2232
Database
ISI
SICI code
1079-5642(200010)20:10<2226:CRPLIM>2.0.ZU;2-V
Abstract
Reperfusion injury after coronary occlusion is in part mediated by leukocyt e activation and adhesion. Platelets may interact with polymorphonuclear gr anulocytes (PMNs), causing aggravated reperfusion injury. We studied whethe r c7E3Fab, a chimeric Fab fragment blocking platelet glycoprotein (GP) IIb/ IIIa, decreases PMN-platelet-dependent myocardial dysfunction after ischemi a. isolated guinea pig hearts (n=5 per group) perfused at a constant flow o f 5 mL/min were subjected to ischemia (15 minutes, 37 degreesC) and reperfu sion. Human PMNs (10 x 10(6) cells, 3 mL), platelets (400 x 10(6), 3 mL), a nd fibrinogen (1 mg/mL) were infused for 3 minutes after 2 minutes of reper fusion, with or without c7E3Fab. Flow cytometry detected GPIIb/IIIa (platel ets) and MAC-1 (aM beta2, PMNs) as well as coaggregates of both in the effl uent, whereas double-fluorescence microscopy visualized intracoronary PMN-p latelet coaggregates. Postischemic recovery of pressure-volume work (12-cm H2O preload and 60-mm Hg afterload) was defined as the ratio of postischemi c to preischemic external heart work (mean+/-SEM). c7E3Fab reduced platelet GPIIb/IIIa detection to 10% of controls. blocked a transcoronary MAC-1 inc rease (+25% without versus -23% with c7E3Fab), and inhibited PMN-platelet c oaggregation 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 hea rt work (83+/-5% in cell-free hearts) declined to 46+/-4% after postischemi c PMN-platelet infusion, but not in the presence of c7E3Fab (74+/-11%) or L PM19c (71+/-6%). We conclude that c7E3Fab inhibits formation of PMN-platele t aggregates during myocardial reperfusion, an effect that protects against PMN-platelet-dependent stunning.