Plaque formation occurs through repetitive injury to the vessel wall. Macrophages and smooth muscle cells are the main cellular elements in plaque development, whereas lipids are the predominant in the extracellular milieu. Plaque fissuring and rupture is affected by features inherent to the plaque, such as its composition and shape, as well as local factors such as shear forces, coronary arterial tone, coronary arterial perfusion pressure, and movements of the artery in response to myocardial contractions. When plaque rupture occurs, potent thrombogenic substances are exposed to circulating platelets.
The platelet response involves adhesion, activation, and aggregation. Platelet adhesion occurs through the weak platelet interactions with subendothelial adhesion molecules such as collagen, fibronectin, and laminin and the binding of the glycoprotein 1b receptor to the subendothelial form of Von Willebrand factor. Adherent platelets are strongly thrombogenic. Subendothelial collagen is a potent inducer of platelet activation. Lipid-laden macrophages in the plaque core and adventitia of the vessel wall release tissue factor, which stimulates the conversion of prothrombin to thrombin. Thrombin, collagen, and the local shear forces are all potent platelet activators. Platelet secretion of adenosine diphosphate, thromboxane A2, and serotonin are autostimulatory agonists of platelet activation. Activated platelet glycoprotein Ilb/IIIa receptors become cross-linked by fibrinogen or Von Willebrand factor in the final common pathway of platelet aggregation.
The extent of oxygen deprivation and thus clinical presentation of acute coronary syndromes, depends upon the limitation of O 2 delivery imposed by thrombus adhering to fixed, fissured, or eroded atherosclerotic plaque. Myocardial ischemia can be manifest by chest discomfort, dyspnea, characteristic or nonspecific electrocardiographic changes, depressed myocardial function, reduced central and peripheral perfusion, or any combination. In stable angina, ischemia occurs only when activity induces O2 demands beyond the supply restrictions imposed by a partially occluded coronary vessel. This occurs at a relatively fixed and predictable point and changes slowly over time. Atherosclerotic plaque has not ruptured and there is little if any superimposed thrombus. In unstable angina and acute myocardial infarction, atherosclerotic plaque rupture and platelet-rich thrombus develops. Coronary blood flow is reduced and myocardial ischemia occurs. The degree and duration of the oxygen supply-demand mismatch determines whether the patient develops reversible myocardial ischemia without injury (unstable angina) or myocardial ischemia with injury (myocardial infarction). More severe obstruction and prolonged obstruction is related to an increased likelihood of myocardial injury.
Acute myocardial ischemia may inhibit myocardial contractability, affecting both central and peripheral perfusion. In acute myocardial infarction, the fundamental alteration is loss of functioning myocardium. When an area of the myocardium does not receive adequate O 2, the functional deterioration is progressive through four sequentially abnormal contraction patterns. Dyssynchrony, the dissociation in time course of contraction of adjacent segments of myocardium, occurs first. Hypokinesis, the reduction in the extent of shortening with contraction, occurs next. Akinesis, the cessation of shortening with systolic contraction follows. Finally dyskinesis, the paradoxical expansion of infarcted tissue, occurs during systole. With increasing size of the infarcted myocardium, left ventricular pump function decreases. Left ventricular end-diastolic pressure increases and left ventricular end-systolic volume increases. Cardiac output, stroke volume, and blood pressure may decrease. When left atrial and pulmonary capillary wedge pressures increase, congestive heart failure may develop. Poor perfusion to the brain and kidneys can result in altered mental status and impaired renal function, respectively.
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