IHD is a consequence of inadequate coronary perfusion relative to myocardial demand, usually as a consequence of a preexisting (“fixed”) atherosclerotic occlusion of the coronary arteries and new, superimposed thrombosis and/ or vasospasm. Atherosclerotic narrowing can affect any of the coronary arteries—left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA)— singly or in combination. Clinically significant plaques tend to occur within the first several centimeters of the LAD and LCX takeoff from the aorta, and along the entire length of the RCA. Sometimes, secondary branches also are involved (i.e., diagonal branches of the LAD, obtuse marginal branches of the LCX, or posterior descending branch of the RCA).
Fixed obstructions that occlude less than 70% of a coronary vessel lumen typically are asymptomatic, even with exertion. In comparison, lesions that occlude more than 70% of a vessel lumen—resulting in so-called “critical stenosis”—generally cause symptoms in the setting of increased demand; with critical stenosis, certain levels of exertion predictably cause chest pain, and the patient is said to have stable angina. A fixed stenosis that occludes 90% or more of a vascular lumen can lead to inadequate coronary blood flow with symptoms even at rest—one of the forms ofunstable angina (see “ ” later in the chapter).
Of importance, if an atherosclerotic lesion progressively occludes a coronary artery at a sufficiently slow rate over years, other coronary vessels may undergo remodeling and provide compensatory blood flow to the area at risk; such collateral perfusion can subsequently protect against MI, even if the original vessel becomes completely occluded. Unfortunately, with acute coronary blockage, there is no time for collateral flow to develop and infarction results.
The following elements contribute to the development and consequences of coronary atherosclerosis:
Inflammation plays an essential role at all stages of atherosclerosis, from inception to plaque rupture (Chapter 10). It begins with the interaction of endothelial cells and circulating leukocytes, resulting in T-cell and macrophage recruitment and activation. These cells drive subsequent smooth muscle cell accumulation and proliferation, with associated matrix production, superimposed on an atheromatous core of lipid, cholesterol, calcification, and necrotic debris. At later stages, destabilization of atherosclerotic plaque can occur through macrophage metalloproteinase secretion.
Thrombosis associated with an eroded or ruptured plaque triggers the acute coronary syndromes. Partial vascular occlusion by a newly formed thrombus on a disrupted atherosclerotic plaque can wax and wane with time and lead to unstable angina or sudden death; alternatively, even partial luminal occlusion by a thrombus can compromise blood flow sufficiently to cause a infarction of the innermost zone of the myocardium (subendocardial infarct). Organizing thrombi produce potent activators of smooth muscle proliferation, which can contribute to the growth of atherosclerotic lesions. Mural thrombi in a coronary artery can also embolize; indeed, small emboli can be found in the distal intramyocardial circulation (along with associated microinfarcts) at autopsy of patients with unstable angina. In the most serious case, completely obstructive thrombus over a disrupted plaque can cause massive MI.
Vasoconstriction directly compromises lumen diameter; moreover, by increasing local mechanical shear forces, vessel spasm can potentiate plaque disruption. Vasoconstriction in atherosclerotic plaques can be stimulated by the following:
Imbalance between endothelial cell–relaxing factors (e.g., nitric oxide) and –contracting factors (e.g., endothelin) due to endothelial dysfunction http://ebooksmedicine.net