PROTECTIVE EFFECTS OF ADENOSINE IN THE REVERSIBLY INJURED HEART

Background. There is substantial evidence that the nucleoside adenosin e reduces postischemic ventricular dysfunction (ie, myocardial stunnin g). Studies performed in our laboratory have attempted to address the mechanism of adenosine-mediated protection of the reversibly injured h eart. Methods. Experiments were performed in isolated perfused rat and rabbit hearts and in in situ canine and porcine preparations. The rol e of adenosine A(1) receptors was assessed by using adenosine A(1) rec eptor agonists and antagonists, and by measuring interstitial fluid pu rine levels with the cardiac microdialysis technique. Results. In isol ated perfused hearts, treatment immediately before ischemia with adeno sine and adenosine A(1) receptor analogues significantly improved post ischemic ventricular function, effects that were blocked by a selectiv e adenosine A, receptor antagonist. In in situ canine and porcine prep arations, pretreatment with adenosine and an adenosine deaminase inhib itor increased preischemic interstitial fluid adenosine levels and att enuated regional myocardial stunning. Adenosine treatment was also ass ociated with improved myocardial phosphorylation potential in isolated guinea pig hearts and in the in situ porcine preparation. Conclusions . These results suggest that adenosine-induced attenuation of myocardi al stunning is mediated via adenosine A, receptor activation and enhan cement of postischemic myocardial phosphorylation potential.