Unstable angina,an acute coronary syndrome,is said to be present when there are episodes of angina at rest and when there is a change in the character,frequency,and duration of chest pain as well as precipitating factors in patients with previously stable angina.Unstable angina is caused by episodes of increased epicardial coronary artery tone or small platelet clots occurring in the vicinity of an atherosclerotic plaque.In most cases,formation of labile nonocclusive thrombi at the site of a fissured or ulcerated plaque is the mechanism for reduction in flow.The course and the prognosis of unstable angina are variable,but this subset of acute coronary syndrome is associated with a high risk of myocardial infarction and death. PATHOPHYSIOLOGY OF ANGINA Determinants of Myocardial Oxygen Demand As a consequence of its continuous activity,the heart's oxygen needs are relatively high,and it extracts approximately 75%of the available oxygen even in the absence of stress.The myocardial oxygen requirement increases when there is an increase in heart rate,contractility,arterial pressure,or ventricular volume.These hemodynamic alterations frequently occur during physical exercise and sympathetic discharge, which often precipitate angina in patients with obstructive coronary artery disease. The heart favors fatty acids as a substrate for energy production.However,oxidation of fatty acids requires more oxygen per unit of ATP generated than oxidation of carbohydrates.Therefore,drugs that shift myocardial metabolism toward greater use of glucose(fatty acid oxidation inhibitors)have the potential of reducing the oxygen demand without altering hemodynamics. Determinants of Coronary Blood Flow Myocardial Oxygen Supply Increased myocardial demands for oxygen in the normal heart are met by augmenting coronary blood flow.Coronary blood flow is directly related to the perfusion pressure (aortic diastolic pressure)and the duration of diastole.Because coronary flow drops to negligible values during systole,the duration of diastole becomes a limiting factor for myocardial perfusion during tachycardia.Coronary blood flow is inversely proportional to coronary vascular bed resistance.Resistance is determined mainly by intrinsic factors including metabolic products and autonomic activity and by various pharmacologic agents.Damage to the endothelium of coronary vessels has been shown to alter their ability to dilate and to increase coronary vascular resistance. Determinants of Vascular Tone Arteriolar and venous tone (smooth muscle tension)both play a role in determining myocardial wall stress.Arteriolar tone directly controls peripheral vascular resistance and thus arterial blood pressure.In systole,intraventricular pressure must exceed 22 Unstable angina, an acute coronary syndrome, is said to be present when there are episodes of angina at rest and when there is a change in the character, frequency, and duration of chest pain as well as precipitating factors in patients with previously stable angina. Unstable angina is caused by episodes of increased epicardial coronary artery tone or small platelet clots occurring in the vicinity of an atherosclerotic plaque. In most cases, formation of labile nonocclusive thrombi at the site of a fissured or ulcerated plaque is the mechanism for reduction in flow. The course and the prognosis of unstable angina are variable, but this subset of acute coronary syndrome is associated with a high risk of myocardial infarction and death. PATHOPHYSIOLOGY OF ANGINA Determinants of Myocardial Oxygen Demand As a consequence of its continuous activity, the heart's oxygen needs are relatively high, and it extracts approximately 75% of the available oxygen even in the absence of stress. The myocardial oxygen requirement increases when there is an increase in heart rate, contractility, arterial pressure, or ventricular volume. These hemodynamic alterations frequently occur during physical exercise and sympathetic discharge, which often precipitate angina in patients with obstructive coronary artery disease. The heart favors fatty acids as a substrate for energy production. However, oxidation of fatty acids requires more oxygen per unit of ATP generated than oxidation of carbohydrates. Therefore, drugs that shift myocardial metabolism toward greater use of glucose (fatty acid oxidation inhibitors) have the potential of reducing the oxygen demand without altering hemodynamics. Determinants of Coronary Blood Flow  Myocardial Oxygen Supply Increased myocardial demands for oxygen in the normal heart are met by augmenting coronary blood flow. Coronary blood flow is directly related to the perfusion pressure (aortic diastolic pressure) and the duration of diastole. Because coronary flow drops to negligible values during systole, the duration of diastole becomes a limiting factor for myocardial perfusion during tachycardia. Coronary blood flow is inversely proportional to coronary vascular bed resistance. Resistance is determined mainly by intrinsic factors including metabolic products and autonomic activity and by various pharmacologic agents. Damage to the endothelium of coronary vessels has been shown to alter their ability to dilate and to increase coronary vascular resistance. Determinants of Vascular Tone Arteriolar and venous tone (smooth muscle tension) both play a role in determining myocardial wall stress. Arteriolar tone directly controls peripheral vascular resistance and thus arterial blood pressure. In systole, intraventricular pressure must exceed