Fig. 11.7 ). In most instances, disruption or erosion of preexisting atherosclerotic plaque serves as the nidus for thrombus generation, vascular occlusion, and subsequent infarction of the perfused myocardium. In 10% of MIs, however, transmural infarction occurs in the absence of occlusive atherosclerotic vascular disease; such infarcts are mostly ascribed to coronary artery vasospasm or to embolization from mural thrombi (e.g., in the setting of atrial fibrillation) or from valve vegetations. Occasionally, especially with infarcts limited to the innermost (subendocardial) myocardium, thrombi or emboli are absent. In such cases, severe fixed coronary atherosclerosis leads to marginal perfusion of the heart. In this setting, a prolonged period of increased demand (e.g., due to tachycardia or hypertension) can lead to ischemic necrosis of endomyocardium, the portion of the heart that is most distal to the epicardial vessels. Finally, ischemia without detectable atherosclerosis or thromboembolic disease can be caused by disorders of small intramyocardial arterioles, including vasculitis, amyloid deposition, or stasis, as in sickle cell disease.
In a typical MI, the following sequence of events takes place:
An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to the blood.
Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine diphosphate (ADP), and serotonin—causing further platelet aggregation and vasospasm (Chapter 4).
Activation of coagulation by exposure of tissue factor and other mechanisms adds to the growing thrombus.
Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen.
The evidence for this scenario derives from autopsy studies of patients dying of acute MI, as well as imaging studies demonstrating a high frequency of thrombotic occlusion early after MI. Angiography performed within 4 hours of the onset of MI demonstrates coronary thrombosis in almost 90% of cases. When angiography is performed 12 to 24 hours after onset of symptoms, however, evidence of thrombosis is seen in only 60% of patients, even without intervention. Thus, at least some occlusions clear spontaneously through lysis of the thrombus or relaxation of spasm. This sequence of events in a typical MI also has therapeutic implications: early thrombolysis and/or angioplasty can be highly successful in limiting the extent of myocardial necrosis.
Loss of blood supply has profound functional, biochemical, and morphologic consequences for the myocardium. Within seconds of vascular obstruction, aerobic metabolism ceases, leading to a drop in adenosine triphosphate (ATP) and accumulation of potentially noxious metabolites (e.g., lactic acid) in the cardiac myocytes. The functional consequence is a rapid loss of contractility, occurring within a minute or so of the onset of ischemia. Ultrastructural changes (including myofibrillar relaxation, glycogen depletion, cellular and mitochondrial swelling) are also seen. These early changes are reversible. Only prolonged ischemia lasting at least 20 to 40 minutes causes irreversible damage and coagulative necrosis of myocytes (Chapter 2). With longer periods of ischemia, vessel injury ensues, leading to superimposed microvascular thrombosis.