Adrenergic mechanisms in myocardial infarction: cardiac and systemic catecholamine release

Abstract

During myocardial ischemia high amounts of noradrenaline are released from the sympathetic nerve terminals of the heart and accumulate in the extracellular space of the ischemic area. This increase in local catecholamine concentrations within the still viable myocardium may induce further deterioration of myocardial function during the ischemic process, i.e., acceleration of cell damage and induction of arrhythmias. Three different mechanisms of local catecholamine release have been demonstrated to operate subsequently during the course of myocardial ischemia. Correspondingly, three phases of release must be considered. Phase 1 (ischemia up to 10 min): The release of catecholamines occurs by exocytosis and depends on the activity of the efferent cardiac sympathetic nerves. The extracellular accumulation of noradrenaline is limited by the activity of the neuronal reuptake process and by presynaptic inhibitory effects of adenosine. Phase 2 (10-40 min of ischemia): A massive accumulation of noradrenaline is found in the extracellular space of the ischemic myocardium. The release is determined by local energy exhaustion rather than by centrally originating factors. The release mechanism is different from exocytosis and demonstrates the characteristics of a carrier-mediated efflux using the neuronal uptake carrier in reverse of its normal transport direction. Phase 3 (ischemia longer than 40 min): The release occurs in parallel with the development of structural membrane defects within the ischemic area and the sympathetic neurons progressively deplete from noradrenaline. Among these mechanisms, the carrier-mediated release of noradrenaline appears to be of greatest significance since during Phase 2, extracellular noradrenaline concentrations reach micromolar concentrations capable of producing myocardial necrosis even in the nonischemic heart.