Multifactorial actions of beta-adrenergic blocking drugs in ischemic heart disease: current concepts.

It is generally agreed that the conditions leading to myocardial ischemia occur when the oxygen demands of the myocardium exceed the oxygen supply. The major limitations of oxygen supply to the myocardium are atherogenic disease and vasospasm of the coronary arteries. The major hemodynamic determinants of myocardial oxygen consumption are systemic wall tension, heart rate and the inotropic state of the myocardium. Stimulation of beta-adrenergic receptors in the heart by endogenous catecholamines increases myocardial oxygen consumption, which can aggravate the ischemic process. Beta-adrenergic blocking drugs decrease myocardial oxygen requirements by reducing systemic arterial pressure, heart rate and myocardial contractility at rest and during exercise, making them useful for treating ischemia. The effects of these drugs on coronary blood flow are less well defined. Beta blockers may decrease coronary blood flow by allowing the unopposed influence of coronary vasoconstrictor impulses to prevail. However, the drugs may also augment overall coronary blood flow by slowing the heart rate and increasing diastolic perfusion time. Controversial studies have shown favorable effects of beta blockers on myocardial metabolism and energetics, the coronary microvasculature, collateral blood flow, the distribution of myocardial blood flow, oxygen-hemoglobin affinity and platelet function. Although their exact antiischemic mechanisms are not known, beta blockers have an overall pharmacologic profile that favors their use in the prevention and treatment of myocardial ischemia.