Hypoxia preconditions rabbit myocardium by an adenosine receptor-mediated mechanism.

ABSTRACT

OBJECTIVES: To test the ability of hypoxia without reoxygenation to precondition myocardium and to test a possible involvement of adenosine receptors in that response. DESIGN: Isolated rabbit hearts were perfused with oxygenated Krebs-Henseleit buffer. Control hearts underwent 30 min regional ischemia followed by 2 h reperfusion. A second group received 10 min global perfusion with hypoxic buffer (PO2 = 33 +/- 3 mmHg) immediately before coronary occlusion. A third group was subjected to a similar protocol as group 2, with the adenosine receptor blocker 8-(p-sulfophenyl) theophylline (SPT) (100 microM) added to the buffer immediately before and throughout hypoxia. At the end of reperfusion the area at risk for infarction was determined by fluorescent particles while infarction size was measured by triphenyltetrazolium staining. RESULTS: Hearts without hypoxic perfusion preceding ischemia experienced 38.2 +/- 2.4% infarction. The hypoxic group, despite a longer total period of oxygen deprivation, had only 21.0 +/- 4.2% infarction (P < or = 0.05). SPT blocked the protection (42.1 +/- 6.9% infarction). CONCLUSIONS: Hypoxia without subsequent reoxygenation before ischemia protected the heart from infarction, indicating that reoxygenation may not be the critical feature of reperfusion typically employed in an ischemic preconditioning protocol. Because adenosine receptor blockade abolishes the protection from hypoxic perfusion, the mechanism of this protection may be similar to that seen with ischemic preconditioning.