Transgenic A1Adenosine Receptor Overexpression Markedly Improves Myocardial Energy State During Ischemia-Reperfusion

A1adenosine (A1AR) activation may reduce ischemia-reperfusion injury. Metabolic and functional responses to 30 min global normothermic ischemia and 20 min reperfusion were compared in wild-type and transgenic mouse hearts with 100-fold overexpression of coupled cardiac A1ARs.31P-NMR spectroscopy revealed that ATP was better preserved in transgenicvwild-type hearts: 53±11% of pre-ischemic ATP remained after ischemia in transgenic heartsvonly 4±4% in wild-type hearts. However, recovery of ATP after reperfusion was similar in transgenic (46±5%) and wild-type hearts (37±12%). Reductions in phosphocreatine (PCr) and cytosolic pH during ischemia were similar in both groups. However, recovery of PCR on reperfusion was higher in transgenic (67±8%)vwild-type hearts (36±8%), and recovery of pH was greater in transgenic (pH=7.11±0.05)vwild-type hearts (pH=6.90±0.02). Bioenergetic state ([ATP]/[ADP].[Pi]) was higher in transgenicvwild-type type hearts during ischemia-reperfusion. Time to ischemic contracture was prolonged in transgenic (13.6±0.8 min)vwild-type hearts (10.4±0.3 min). Degree of contracture was lower and recovery of function in reperfusion higher in transgenicvwild-type hearts. In conclusion, A1AR overexpression reduces ATP loss and improves bioenergetic state during severe ischemic insult and reperfusion. These changes may contribute to improved functional tolerance.