Adenosine protects against hypoxic injury at hypothermia in guinea pig papillary muscles

Objectives. To investigate the protective effects of adenosine against hypoxic injury at hypothermia; both magnitude and mechanisms. Design. Receptor versus non-receptor dependent mechanisms in cardioprotection by adenosine were examined in guinea pig papillary muscles exposed to glucose free hypoxia at 24 degrees C. Contractile force amplitude (CFA) and action potential duration (APD) during increasing concentrations of adenosine at 37 degrees C, 30 degrees C and 24 degrees C normoxia were also examined. Results. CFA was significantly improved after adenosine treatment during hypothermic hypoxia compared to control (80.7 +/- 17.4% vs 40.5 +/- 10.7%, p < 0.001). Adenosine receptor antagonist SPT did not antagonize (64.6 +/- 21.1%), and adenosine receptor agonists (APNEA + NECA) could not mimic the cardioprotection (53.8 +/- 9.3%). MitoK(Ca) blocker paxilline antagonized the cardioprotection (40.0 +/- 7.7%). During normoxic conditions hypothermia-induced increase in CFA was significantly decreased by adenosine (0.12-12 mM) whereas the increase in action potential duration was potentiated. Conclusion. Adenosine (1.2 mM) had marked cardioprotective effect in hypothermic substrate free hypoxia. Possible mechanisms are non-receptor dependent and related to mitoK(Ca) channels. The cardiodepressive effect at hypothermia may contribute to cardioplegia.