ISCHEMIC PRECONDITIONING IN HUMAN AND RAT VENTRICLE

The signal transduction of ischemic preconditioning involves activatio n of endogenous receptor-based systems, including alpha(1)-adrenocepto rs and adenosine receptors. Whereas preconditioning protects against i schemia-reperfusion injury, it is unknown whether this protective stra tegy might be useful clinically. Furthermore, human atrium has been su ccessfully preconditioned, but it is unknown whether human ventricle c an be functionally protected against hypoxia-reoxygenation. To study t hese questions, isolated rat ventricle and human ventricular trabecula e were suspended in an organ hath and subjected to 30 min of hypoxia a nd 60 min of reoxygenation. In the rat ventricle, preconditioning was induced by 5 min of rapid pacing at 3 Hz in hypoxic buffer without glu cose (simulated ischemia), alpha(1)-adrenoceptor stimulation (phenylep hrine), or adenosine receptor stimulation (adenosine). In the human tr abeculae the effects of preceding simulated ischemia and alpha(1)-adre noceptor and adenosine receptor stimulation were examined against hypo xia-reoxygenation. In the rat, pretreatment with simulated ischemia an d alpha(1)-adrenoceptor and adenosine receptor stimulation improved re covery of developed tension (56 +/- 3, 56 +/- 4, and 58 +/- 2%, respec tively) compared with control trabeculae (25 +/- 2%) after hypoxia-reo xygenation (P < 0.05). in human trabeculae, simulated ischemic precond itioning and alpha(1)-adrenoceptor and adenosine receptor stimulation augmented recovery of developed tension (65 +/- 5, 59 +/- 6, and 60 +/ - 3%, respectively) compared with control (29 +/- 2%) after hypoxia-re oxygenation (P < 0.05). We conclude that functional cardioadaptation ( preconditioning) against hypoxia-reoxygenation injury in rat and human myocardium exists and that alpha(1)-adrenergic and adenosine receptor signaling participate in conferring this protection.