Pathophysiology of Myocardial Ischemia & Acute Coronary Syndromes

Advanced coronary atherosclerosis and even complete occlusion may remain clinically silent. There is only a modest correlation between the clinical symptoms and the anatomic extent of disease. At present, the only means of determining the location and extent of narrowing is coronary arteriography, although ischemia can be recognized by other less invasive studies.

Myocardial ischemia may be provoked by either increased myocardial oxygen requirements (exercise, mental stress, or spontaneous fluctuations in heart rate and blood pressure) or by decreased oxygen supply (caused by coronary vasospasm, platelet plugging, or partial thrombosis).

Abnormal endothelial function appears to play a role in the fluctuating threshold for ischemia; impaired release of nitric oxide (endothelium-derived relaxing factor) may permit unopposed vasoconstriction and facilitate platelet adhesion.

In angina pectoris, increased oxygen demand is the most frequent mechanism. In contrast, the acute coronary syndromes of unstable angina and myocardial infarction are caused by plaque disruption, platelet plugging, and coronary thrombosis. Of interest is the predilection for these episodes to occur in the early morning or shortly after arising. The outcome of this series of events is determined by whether the vessel becomes occluded or whether thrombolysis occurs, either spontaneously or as a result of treatment, and whether the plaque subsequently becomes stabilized. Thus, therapy is primarily directed toward inhibition of platelet activity (aspirin, clopidogrel, IIb/IIIa receptor antagonists), antithrombotic agents (the heparins), and thrombolysis in acute syndromes and toward minimizing myocardial oxygen requirements - as well as preventive measures - in chronic angina.

Some episodes of myocardial ischemia are painful, causing angina pectoris; others are completely silent. Many silent episodes are brought on by emotional and mental stress. In patients with diagnosed coronary disease, as evidenced by prior myocardial infarction or angina, silent ischemic episodes have the same prognostic import as painful ones. The prognosis for patients with only silent ischemia is not well established, nor is the potential benefit of preventing silent ischemia.

Brogan GX Jr: Bench to bedside: pathophysiology of acute coronary syndromes and implications for therapy. Acad Emerg Med 2002;9:1029.
Servoss SJ et al: Triggers of acute coronary syndromes. Prog Cardiovasc Dis 2002;44:369.
Shah PK: Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis 2002; 44:357.

Myocardial Hibernation & Stunning

Areas of myocardium that are persistently underperfused but still viable may develop sustained contractile dysfunction. This phenomenon, which is termed myocardial hibernation, appears to represent an adaptive response but may lead to left ventricular failure. It is important to recognize this phenomenon, since this form of dysfunction is reversible following coronary revascularization. Hibernating myocardium can be identified by radionuclide testing, positron emission tomography, contrast-enhanced MRI, or its retained response to inotropic stimulation with dobutamine. A related phenomenon, termed myocardial stunning, is the occurrence of persistent contractile dysfunction following prolonged or repetitive episodes of myocardial ischemia.