Beta-adrenergic mechanisms during severe myocardial ischemia and evolving infarction.

Severe myocardial ischemia and infarction cause release of catecholamines, with exposure of injured myocardial cells to relatively high concentrations during the transitional period in which myocyte injury worsens. In experimental animals, the number of beta-adrenergic receptors increases markedly without any change in affinity within one hour of coronary artery occlusion, and the number of alpha-adrenergic receptors also increases. Stimulation by exogenous cate-cholamines during a period of reperfusion one hour after temporary coronary occlusion is associated with an enhanced biochemical response in the ischemic myocardium. Administration of beta-adrenergic blockers prior to or within a few minutes after occlusion limits the extent of myocardial necrosis. In clinical studies, administration of propranolol, timolol, or metoprolol has been shown to significantly reduce the mortality rate after myocardial infarction (MI). Administration of timolol or metoprolol also reduces the frequency of recurrent MI. Beta-adrenergic blockers may prolong life and reduce the risk for recurrent MI by antagonizing and/or preventing basic biologic alterations in injured myocytes and/or by antagonizing detrimental effects of the relatively high concentrations of catecholamines to which these cells are exposed. Increased number of beta-adrenergic receptors, the ability to translate adrenergic stimulation into intracellular metabolic events, and increased local concentrations of catecholamines may be important factors in arrhythmogenesis and myocyte injury during severe myocardial ischemia and evolving MI.