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 myocardium. To elucidate a possible mechanism isolated rabbit hearts were subjected to a 30-min period of regional ischemia by occluding a previously snared coronary artery. Following 2 h of reperfusion infarct size was measured by staining left ventricular slices with triphenyltetrazolium chloride. In control hearts infarction averaged 28.7 +/- 1.9% of the risk zone. If the hearts were preconditioned with 5 min global ischemia/10 min reperfusion prior to the regional ischemia, then infarction was significantly reduced to 7.2 +/- 2.0% (P < 0.01). When global hypoxia (pO2 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 control). During hypoxic perfusion adenosine release increased 16-fold over baseline levels. This protection could not be blocked by adding levels either the adenosine antagonist 8-(p-sulfophenyl)theophylline or the alpha 1-adrenergic blocker phenoxybenzamine to the hypoxic perfusate. However, co-administration of both agents to the hypoxic perfusate successfully aborted protection (22.6 +/- 2.9% infarction, P N.S. v control). Therefore, 10 min of hypoxia releases both norepinephrine and adenosine in sufficient quantities such that either can completely precondition the heart.