Insights into the pathogenesis of acute ischemic syndromes.

OVER THE LAST few years clinical/pathologic observations and experimental investigation have led us to a better understanding of the pathogenetic factors leading to the acute coronary syndromes: unstable angina , myocardial infarction, and ischemic sudden death. The elegant pathologic studies of Falk' and Da-vies and Thomas2 have emphasized that thrombus formation secondary to plaque rupture and fissuring in the atherosclerotic coronary artery play a major and frequent role in the acute coronary syndromes. Indeed, their observations and the observations of others have established that this pathologic phenomenon is a common link between the three acute coronary syndromes in man.3 This review focuses on three areas of recent progress: (1) the interaction between platelets, thrombosis , and blood rheology in experimental vessel wall injury, (2) the relevance of these blood vessel interactions to the acute coronary syndromes in man, and briefly (3) the usefulness of antithrombotic therapy in reducing morbidity and mortality due to the acute coronary syndromes. Interaction of platelets, thrombosis, and blood rheology in experimental vessel wall injury Platelet adhesion in experimental mild superficial vessel wall injury (figure 1). After removal of the endothelial lining of a normal blood vessel by a mild or superficial injury , the subendothelium becomes coated by a layer of adherent platelets. Adhesion, the process by which platelets attach to the exposed subendothelium, is dependent on platelet receptors and adhesive membrane glycoproteins, and on exposure of activating sites in the subendothelium4 (figure 1). Glycoprotein lb in the platelet membrane appears to be important for normal initial contact of platelets with von Willebrand factor in the subendothelial surface. binds directly to exposed subendothelial collagen, may also be important. Glycoprotein IIb/IIla in the platelet membrane is the receptor for a variety of circulating proteins, including von Willebrand factor and fibro-nectin, and aside from being important in platelet ag-gregation (see later), it indicates platelet adhesion. In the clinical context, subtle injury of the endotheli-al cell layer, for example that produced by flowing blood at arterial branch points or through stenoses, may trigger platelet adhesion. The release of platelet-derived growth factors after platelet adhesion may contribute to the slow process of atherogenesis. Platelet aggregation and thrombosis in experimental deep vessel wall injury (figure 1). Severe injury exposes components of the arterial media, particularly fibrillar colla-gen (with type I being more prevalent in diseased vessels and type III in normal vessels5), which in addition to other mediators, induces platelet …