Mediation of Platelet and Coagulation Events by Blood Flow: Basic Mechanisms of Thrombosis in Cerebral Ischemia

Abstract

Atherosclerosis is the principal underlying disease process in myocardial and cerebral infarction and is the major cause of death in the United States and Western Europe [22]. Recent studies have delineated the importance of thrombosis in the latter stages of atherosclerotic disease [1, 10, 11]. While there is limited evidence that thrombotic events contribute to the progression of atherosclerotic narrowing of the vessel lumen [18, 44], there is little doubt that in a majority of cases, final vascular occlusion is associated with thrombotic deposits [11]. The mechanisms by which thrombi form in the vicinity of a stenotic lesion are not fully understood, but clearly involve the local blood flow conditions, the composition of the underlying vascular material, and the participation of certain blood factors [14, 35, 36]. While considerable effort has been expended in uncovering the biochemical mechanisms in the blood and vascular wall which lead progressively to atherosclerotic disease, little emphasis has been focused on the fluid dynamic factors which modulate the disease process. It has long been known that initiation and progression of vascular lesions occur at sites which are distinguished primarily by the local fluid dynamic conditions; that is, lesions are characterized by their focal, rather than ubiquitous nature [19, 21]. Both high and low shear stresses have been implicated in the pathogenesis of arterial disease [12, 15, 18, 45, 46], and early fluid dynamic studies were primarily directed at a delineation of local flow disturbances at vascular bifurcations and sinuses or in geometrical models of atherosclerotic lesions.