Protection from myocardial stunning by ischaemia and hypoxia with the adenosine A3 receptor agonist, IB-MECA

Guinea pig isolated working hearts were exposed to 30-min ischaemia by reducing coronary flow to 10%, followed by reperfusion. Aortic output fell to 4.5±4.5% of the pre-ischaemic value at reperfusion, recovering to 48.2±14.6% at 20-min post-reperfusion; the index of myocardial stunning. IB-MECA (N6-(3-iodobenzyl)adenosine-5′-N-methyluronamide, 3×10−7 M), infused from 10 min into ischaemia, did not affect recovery of aortic output 20 min after reperfusion (41.9±1.9%). IB-MECA infused at reperfusion, however, significantly protected against stunning, aortic output recovering to 79.6±3.9% at 20-min post-reperfusion. Hypoxic gassing (5% CO2 in nitrogen, 30 min) of guinea pig isolated paced left atria and papillary muscles reduced the developed tension, recovering to 75% 5 min after re-oxygenation. This myocardial stunning was unaffected by IB-MECA (3×10−7 M) added 10 min into hypoxia. IB-MECA added at reoxygenation significantly improved recovery, which was prevented by the adenosine A3 receptor antagonist, 1-propyl-3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenylxanthine (I-ABOPX, 1×10−5 M). Thus, stimulation of adenosine A3 receptors at reperfusion/reoxygenation in guinea pig cardiac preparations protects against myocardial stunning.