HYPOXIA PRECONDITIONS RABBIT MYOCARDIUM VIA ADENOSINE AND CATECHOLAMINE RELEASE

it has been proposed that brief hypoxia can substitute for ischemia in the preconditioning of cardiac tissue and salvage of ischemic myocard ium. To elucidate a possible mechanism isolated rabbit hearts were sub jected to a 30-min period of regional ischemia by occluding a previous ly snared coronary artery. Following 2 h of reperfusion infarct size w as measured by staining left ventricular slices with triphenyltetrazol ium chloride. In control hearts infarction averaged 28.7 +/- 1.9% of t he risk zone, If the hearts were preconditioned with 5 min global isch emia/10 min reperfusion prior to the regional ischemia, then infarctio n was significantly reduced to 7.2 +/- 2.0% (P<0.01). When global hypo xia (pO(2) of perfusate 42.0 +/- 2.1 mmHg) for ten min substituted for the five min period of global ischemia, protection was comparable to that observed after ischemic preconditioning (10.2 +/- 1.5% infarction , P<0.01 v central). During hypoxic perfusion adenosine release increa sed 16-fold over baseline levels. This protection could not be blacked by adding either the adenosine antagonist 8-(p-sulfophenyl)theophylli ne or the alpha(1)-adrenergic blocker phenoxybenzamine to the hypoxic perfusate. However, co-administration of both agents to the hypoxic pe rfusate successfully aborted protection (22.6 +/- 2.9% infarction, P N .s. v control). Therefore, 10 min of hypoxia releases both norepinephr ine and adenosine in sufficient quantities such that either can comple tely precondition the heart. (C) 1995 Academic Press Limited