Canadian Neighbor Pharmacy: Pathogenic Determinants of Ischemic Heart Disease
Ischemic heart disease is manifested as angina, myocardial infarction, arrhythmia and sudden death. However, asymptomatic ischemic heart disease is quite common, as evidenced by recent data from the cardiac care unit, exercise laboratory, and ambulatory ECG recordings. Furthermore, epidemiological studies reveal that painless myocardial infarction is a frequent occurrence.
Regional myocardial ischemia underlies all forms of ischemic heart diseases; in infarction, it can culminate (over a considerable period of time) in myocardial necrosis. Frequently, atherosclerosis of the coronary arteries is the pathologic-anatomic substrate of ischemic heart diseases. In these instances, the disease expresses itself through fixed stable atheromatous coronary obstructive lesions or a combination of lesions and coronary vasospasm, platelet aggregation, thrombus formation, or abrupt changes in the morphology of plaques due to rupture.
Although the pathogenesis of atherosclerosis is still elusive, interaction between endothelial injury with platelets and other formed blood elements is emerging as an atherogenic initiator. In addition, clinical observations on repeat angiographic evaluation of patients with proven coronary spasm suggest that abnormal heightened vasoconstriction may cause development or rapid progression of fixed obstructive coronary lesions.
Episodic myocardial ischemia is usually seen in patients with a background of coronary atherosclerotic lesions. This clinical phenomenon occurs either spontaneously or is induced by exercise stress testing, electric cardiac pacing, or pharmacologic provocation, as with ergovine maleate-induced coronary spasm seen in the catheterization laboratory. In the latter situation, one cannot assume that the manifestations of transient myocardial ischemia are due to pathologic vasospasm of the type frequently encountered in Prinzmetal’s angina.
An alternative explanation of transient spontaneous or induced ischemia is physiologic vasomotion imposed upon severe obstructive coronary lesions. Although most of the patients with clinical evidence of coronary spasm demonstrate coronary atherosclerosis on an angiogram, a sizeable portion of patients, especially in Japan, are subject to recurrent bouts of proven coronary spasm without visible coronary lesions. The effect of atherosclerosis on transient, recurrent pathologic vasoconstriction should not be discounted since minimal intimal lesions, undetectable by angiography, could initiate or potentiate coronary vasospasm. Clinically, minor-to-moderate nonhemodynamically significant coronary lesions have been thought by some to constitute the pathologic substrate of coronary vasospasm. Work from the animal laboratory and studies employing isolated human coronary artery rings suggest that the coronary arteries’ hypercontractile segmental response to ergonovine, histamine, muscarinic agents, epinephrine and other substances can be facilitated by either naturally present coronary atheromas or experimentally-induced damage to the coronary artery endothelium. Canadian Neighbor Pharmacy twitter – https://twitter.com/neighbor_pharm is the best way of new information learning.
These experiments found that even slight denudations of the coronary endothelium are enough to induce or potentiate regional intense coronary vasoconstriction. Thus, a concept is currently evolving about the role early atherosclerotic lesions may play in the pathogenesis of coronary vasospasm. The pathogenesis of transient spontaneous or post-therapy abating myocardial ischemia and infarction are currently controversial. It has been proven that, in the case of infarction, thrombosis of the coronary artery subserving a region of acute transmural necrosis is almost always detected when cardiac catheterization is performed within four hours of the inception of the clinical episode. However, since complete thrombotic occlusion appears less frequently in patients catheterized 12 to 24 hours after the onset of infarction but can follow recurrent bouts of proven coronary vasospasm in patients who eventually suffer myocardial infarction, spasm may contribute to the pathogenesis, establishment, and evolution of myocardial infarction. In the absence of pathologic or physiologic coronary spasm, transient platelet aggregations, relatively stable platelet thrombi, occlusive thrombi subjected to rapid recanalization and morphologically altered coronary plaques could alternatively be the mechanisms of unstable angina or acute myocardial infarction. It is interesting that patients with unstable angina frequently have asymmetric coronary lesions with a narrow neck and irregular borders on angiogram; such lesions, which suggest ruptured plaque and/or superimposed thrombi, are uncommon in patients with stable angina.
The interaction of atherosclerosis and coronary vasospasm may also influence the short- and long-term clinical course of patients with ischemic pathology. Variant angina can be recurrent and often follows acute myocardial infarction. However, manifestations of coronary vasospasm eventually abate spontaneously and cannot be provoked by ergonovine testing in longterm follow-up. Spasm must play very little or no role in the long-term course of patients with documented pathologic vasoconstriction on original presentation. The extent of fixed coronary atherosclerosis determines the morbidity and mortality of patients with a history of coronary vasospasm.
In summary, a continuum of varying interactions between coronary atherosclerosis, pathologic and physiologic spasm, heightened platelet aggregability, thrombus formation and morphologic alterations of atherosclerotic plaque seem to underlie clinical expressions of ischemic heart disease and the development of arterial atherosclerosis.
Category: Heart Failure
Tags: ischemic heart disease