Alpha-adrenoceptor stimulation with exogenous norepinephrine or release of endogenous catecholamines mimics ischemic preconditioning.

Abstract

BACKGROUNDBrief episodes of ischemia induced by proximal coronary artery occlusion can precondition the myocardium. Whether other stressful stimuli have the potential to protect the myocardium from subsequent ischemia remains controversial.METHODS AND RESULTSTo study the hypothesis that transient alpha-adrenoceptor stimulation mimics preconditioning, for 5 minutes we administered 0.25 micrograms.kg-1.min-1 norepinephrine or saline 10 minutes before a 30-minute coronary occlusion and 4 hours of reperfusion in an in vivo rabbit model. The area of necrosis (AN) and area of risk (AR) were measured. We found that norepinephrine pretreatment caused a reduction in infarct size when compared with controls (AN/AR, 0.17 +/- 0.04 versus 0.31 +/- 0.04; P < .02). Ischemic preconditioning also reduced infarct size (AN/AR, 0.22 +/- 0.03). The protection observed with norepinephrine treatment was entirely eliminated by pretreatment with alpha-adrenergic blockade using prazosin (AN/AR, 0.42 +/- 0.06). Tyramine, an agent t...