Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention (original) (raw)

CUTE ST-ELEVATION MYOCARdial infarction (STEMI) constitutes a major public health problem, not only in western countries but increasingly in developing countries. 1 In the United States, there are estimated to be more than half a million STEMI events annually and these have provided strong impetus for efforts to improve both the process whereby care is delivered and the treatment elements administered. 2 Although reperfusion with primary percutaneous transluminal coronary intervention (PCI) is highly effective, especially if delivered promptly in an expert facility, it is now appreciated that not all PCIs adequately restore myocardial or tissue perfusion. 3 Reperfusion achieved through primary PCI and coronary stenting may be associated with distal coronary embolization, endothelial dysfunction, and impaired ventricular function. 4 A concomitant inflammatory reaction, participating in the accompanying reperfusion injury may mediate apoptosis in the periinfarction area and unfavorable left ventricular remodeling. 5 Poor tissue perfusion and the intensity of the inflammatory response are related to subsequent mortality. 4,6 Complement is known to be both activated and a potential mediator of these processes, and activation of the terminal components of the complement cascade leads to cleavage of the C5 component: this in turn results in formation of both C5a, a potent anaphylatoxin and proinflammatory substance, and C5b-9 or the membrane attack complex (MAC), which causes vesiculation of platelets and endothelial cells, formation of prothrombotic microparticles, and activation of leu-kocytes and endothelial cells. Hence, inhibition of C5 constitutes an attractive therapeutic target. 7 For editorial comment see p 91.

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