The dog model shows that a regional infarct is produced when flow is abolished in the artery subtending that region. This is also true of human infarction. The predominant cause of human arterial occlusion is thrombosis superimposed on pre-existing atherosclerosis. Rare causes are coronary spasm, either spontaneous or due to cocaine, coronary dissection, coronary emboli, and localized arteritis. About a quarter of major thrombi are due to superficial loss of the endothelium over a plaque with exposure of the underlying connective tissue matrix to platelets, leading to a thrombus which is attached to the luminal surface of the plaque. Plaque disruption is responsible for most thrombi (DaviesJ990) and is a complication of plaques (American Heart Association types IV and Va) (Stary.eta[ 1995) which have a core of extracellular lipid separated from the arterial lumen by a cap of fibromuscular tissue. The core contains abundant macrophages expressing tissue factor. In disruption the plaque cap tears (Fig 1), allowing blood from the lumen to enter the core where a platelet-rich thrombus forms. A second stage follows in which thrombus projects into but does not occlude the lumen; in the third stage thrombus occludes the lumen. Platelets are a major component of the first two stages; in the third stage the thrombus is rich in fibrin and enmeshed red cells. A range of factors may accelerate or inhibit this staged thrombotic response ( Fig 1), which is dynamic; intermittent occlusion is common (stuttering onset). Unstable angina is associated with non-occluding mural thrombus. Transient episodes of myocardial ischemia are caused by platelet emboli from the surface of the exposed mural thrombus impacting in the intramyocardial vascular bed. These microemboli cause microscopic foci of necrosis (Davies .etal 1986).
Plaques at high risk of disruption (i.e. vulnerable) can be angiographically invisible or cause any degree of stenosis. Total thrombotic occlusion of a coronary artery in which there is no prior stenosis, and therefore no collateral flow, is more likely to cause infarction than thrombosis at sites of previous high-grade stenosis. Previous angina also invokes preconditioning of the myocardium and limits infarction.
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