The greater incidence of anginal attacks in the morning hours may be indirect evidence of increased coronary artery tone. The sympathetic stimulation that takes place upon awakening and arising is an important mediator of the increase in blood pressure, heart and myocardial contractility which occur in the morning causing an increase in oxygen consumption and changes in vasomotor tone.
Added factors in the etiology of painful and painless episodes are the transient alterations in coronary blood flow (inadequate supply), in contrast to a disproportionate increase in myocardial demand. Since approximately 75 percent of plaques are eccentric and pliable, the “free” vessel wall devoid of rigid atheromata experience changes in tone and contractility adding a dynamic component to a stable flow limiting lesion.
Attention has been focused on factors controlling coronary arterial blood flow. The paramount role of the coronary arteries in modulating myocardial perfusion is the basis for a new understanding of the pathophysiology of myocardial ischemia. The vessel wall is now viewed as the center of multiple and complex interactions between neurohumeral, hemodynamic and vascular factors which may result in static or dynamic artery stenosis. Changes in resistance at the site of the flow-limiting stenosis have been postulated to explain the variability of coronary flow reserve and consequently the changes in ischemic threshold. These changes are likely a reflection of alterations in coronary vessel “basal” tone, compliance and reactivity in response to various stimuli. The most conspicuous segment of the vessel wall, the endothelium, has been the subject of extensive research. The growing understanding of its role in regulating vascular tone and reactivity has resulted in a more comprehensive delineation of the potential mechanisms of coronary ischemia. By virtue of its strategic location at the vessel lining, the endothelial cell interacts with the humeral and cellular elements of the blood as well as with the adjacent components of the vessel wall. The endothelial cells possess multiple metabolic properties that act as a permeability barrier, processing circulating hormones, and releasing bioactive substances with great efficiency and selectivity. In addition to the multiple surface properties and physiologic functions of the endothelial cell there is concrete evidence for active interactions with adjacent cells. Their role in regulating vascular smooth muscle tone and permitting the unified operation of all the components of the vessel wall has been clearly established. viagra jelly online
The vascular endothelium, when stimulated, can generate a number of vasoactive substances. In the presence of a normal endothelium, in situ platelet activation and aggregation and subsequent release of vasoactive mediators (vasopressin, adenosine triphosphate, adenosine diphosphate, platelet activating factor, serotonin, and thromboplastin) stimulate the endothelial production of relaxing factors (endothelial-derived relaxing factor) that inhibit the contractility of the adjacent smooth muscle. Simultaneous activation of the prostaglandin cascade (cyclo-oxygenase pathway) leads to the formation of prostacyclin, a potent vasodilator and antiaggregatory substance, thereby providing synergistic protection against coronary vasospasm. In addition, an intact endothelial lining is an effective biologic barrier that prevents the diffusion of vasoactive agents into the vessel wall.
The evidence that links endothelial injury to fixed obstructive ischemic heart disease is well established. In atherosclerotic coronary artery disease, the formation and progression of an atheromatous plaque produce both functional and morphologic disruption of the endothelial cell monolayer causing critical alterations in mechanisms of cell-to- cell interactions. A number of recent studies have demonstrated that endothelial dysfunction may be present even at the early stages of atheromatous transformation of the vessel wall. Impaired formation of endothelial-derived relaxing factor in response to acetylcholine has been postulated as the mechanism responsible for the paradoxic vasoconstrictive effect of this substance in patients with atherosclerosis.
Moreover, acute anoxia inhibits the release of endothelial- derived relaxing factor and triggers the generation of endothelial-derived contracting factors, which may enhance and perpetuate vasoconstriction. With more advanced atheromatous lesions, endothelial damage leads to cell death and denudation of the vessel lining, allowing the exposure of collagen, remnants of basement membrane, and myocytes to the circulation, which in turn triggers platelet aggregation. The consequences of the unopposed action of platelet- derived vasoconstriction agents and procoagulant substances superimposed on a fixed subocclusive coronary lesion are predictable, that is, local vasospasm and thrombosis. Further tissue anoxia perpetuates this vicious cycle. Finally, a complex interaction between circulating blood elements, physical factors and the vessel wall may lead to local thrombogenesis. As described by Virchow, intravascular thrombosis can result from abnormalities in blood components, circulatory stasis and disruption of the integrity of the vessel wall.
The limitation of coronary flow by a synergetic action of semi-rigid subintimal atheroma and segmental vascular contractions results in greater stenosis, local turbulence and stagnation. In situ activation of platelets by mechanical factors and physiochemical interactions with the vessel wall enhances the thrombogenic potential of acute circulatory impairment, and results in coronary artery thrombosis distal to the atherosclerotic site. Other mechanisms, such as rupture of an atherosclerotic plaque may not represent the triggering events for local thrombogenesis. In situ coronary thrombosis of the artery supplying the affected area can be found in up to 90 percent of patients with transmural myocardial infarction and in 20-50 percent of nontransmural myocardial infarction. It is also highly prevalent in syndromes of unstable angina where it may be found in up to 80 percent of patients.
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Additionally, changes in autonomic tone associated with the awakening-arousing phenomenon have been clearly implicated in the pathogensis of a hypercoagulable state during the morning hours, and in the generation of a transmural pressure gradient which could potentially cause intramural hemorrhage and plaque rupture.
Incidence of silent ischemia
a. asymptomatic middle age men <10 (35-60 years)
f myocardial infarction 20-30
g. post myocardial infarction with >50 poor left ventricular function andJ or arrhythmias.
Silent myocardial ischemia is a frequent finding in patients with known coronary artery disease. The Framingham study has shown that of all new infarcts, the incidence of acute silent myocardial infarction ranged from 27.7 percent in men to 34.7 percent in women. Silent ischemia is also common following acute myocardial infarction. Early postinfarction stress testing has shown that in Q-wave infarction the incidence of silent ischemia is about 18 percent and in non-Q wave infarction as high as 60 percent. Furthermore, in selected populations, episodes of silent ischemia may represent up to 90 percent of ischemic events. In patients unable to undergo exercise stress testing due to severe sequelae following myocardial infarction (poor left ventricular function or arrhythmias) ambulatory monitoring has shown that the incidence of silent ischemia can be as high as 50 percent. In patients with exertional angina, silent episodes may outnumber painful attacks by three to four, and the overall incidence of silent ischemia ranges from 40 to 50 percent.
In contrast, the highest incidence of silent ischemia occurs in patients with unstable angina. Sixty percent of these patients have silent ischemia and 90 percent of ischemic events are painless. Moreover, in patients with coronary artery disease hospitalized for unstable angina, the duration of silent ischemia has been shown to be a marker for adverse outcome. Finally, the incidence of asymptomatic coronary artery disease detected by a 24-hour ambulatory electrocardiographic recording is estimated to be 2.5 to 10 percent in males between the age of 35 to 60 years.
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