Dose-dependent effects of adenosine on interstitial fluid adenosine and postischemic function in the isolated rat...

Exogenous adenosine produces numerous beneficial effects in ischemic myocardium, but pharmacological doses of adenosine are required to exert these effects. This is thought to be due to the rapid metabolism of adenosine by coronary endothelium, although there is no direct evidence supporting this hypothesis in the ischemic/reperfused heart. The purpose of this study was to determine the relationship between vascular and interstitial fluid (ISF) adenosine levels during adenosine-induced cardioprotection. Isolated perfused rat hearts were submitted to 30-min global normothermic ischemia and 30- min reperfusion. Left ventricular developed pressure (LVDP) was measured with a fluid-filled latex balloon, and ISF adenosine was estimated with cardiac microdialysis. Control hearts were compared with hearts treated with increasing doses of adenosine (1, 10 and 100 microM) for 10 min immediately preceding ischemia. Adenosine produced dose-dependent increases in coronary effluent adenosine levels, but only 10 and 100 microM adenosine increased dialysate adenosine concentrations. All adenosine doses increased coronary flow to the same extent, but only the two higher doses decreased spontaneous heart rate. Control and 1 microM adenosine-treated hearts recovered 60 +/- 3% and 46 +/- 7% of preischemic LVDP, respectively, whereas 10 and 100 microM adenosine improved recovery to 80 +/- 5% and 90 +/- 4% of preischemic LVDP, respectively, after 30-min reperfusion. Because ISF bathes the cardiac myocytes, these results are consistent with the hypothesis that adenosine protects the ischemic rat heart via the activation of cardiac myocyte adenosine receptors.