Infarction is tissue death caused by ischaemia. Acute myocardial infarction (MI) occurs when localized myocardial ischaemia causes the development of a defined region of necrosis. MI is most often caused by rupture of an atherosclerotic lesion in a coronary artery. This causes the formation of a thrombus that plugs the artery, stopping it from supplying blood to the region of the heart that it supplies.
Role of Thrombosis in MI
Pivotal studies by DeWood and colleagues showed that coronary thrombosis is the critical event resulting in MI. Of patients presenting within 4 h of symptom onset with ECG evidence of transmural MI, coronary angiography showed that 87% had complete thrombotic occlusion of the infarct-related artery. The incidence of total occlusion fell to 65% 12–24 h after symptom onset due to spontaneous fibrinolysis. Fresh thrombi on top of ruptured plaques have also been demonstrated in the infarct-related arteries in patients dying of MI.
Mechanisms and Consequences of Plaque Rupture
Coronary plaques that are prone to rupture are typically small and non-obstructive, with a large lipid-rich core covered by a thin fibrous cap. These ‘high-risk’ plaques typically contain abundant macrophages and T lymphocytes which are thought to release metalloproteases and cytokines that weaken the fibrous cap, rendering it liable to tear or erode due to the shear stress exerted by the blood flow.
Plaque rupture reveals subendothelial collagen, which serves as a site of platelet adhesion, activation and aggregation. This results in:
The endothelium is often damaged around areas of coronary artery disease. The resulting deficit of antithrombotic factors such as thrombomodulin and prostacyclin enhances thrombus formation. In addition, the tendency of several platelet-derived factors (e.g. TXA2, 5-HT) to cause vasoconstriction is increased in the absence of endothelial-derived relaxing factors. This may promote the development of local vasospasm, which worsens coronary occlusion.
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