Protective effects of adenosine in the reversibly injured heart.

Abstract

There is substantial evidence that the nucleoside adenosine reduces postischemic ventricular dysfunction (ie, myocardial stunning). Studies performed in our laboratory have attempted to address the mechanism of adenosine-mediated protection of the reversibly injured heart. Experiments were performed in isolated perfused rat and rabbit hearts and in in situ canine and porcine preparations. The role of adenosine A1 receptors was assessed by using adenosine A1 receptor agonists and antagonists, and by measuring interstitial fluid purine levels with the cardiac microdialysis technique. In isolated perfused hearts, treatment immediately before ischemia with adenosine and adenosine A1 receptor analogues significantly improved postischemic ventricular function, effects that were blocked by a selective adenosine A1 receptor antagonist. In in situ canine and porcine preparations, pretreatment with adenosine and an adenosine deaminase inhibitor increased preischemic interstitial fluid adenosine levels and attenuated regional myocardial stunning. Adenosine treatment was also associated with improved myocardial phosphorylation potential in isolated guinea pig hearts and in the in situ porcine preparation. These results suggest that adenosine-induced attenuation of myocardial stunning is mediated via adenosine A1 receptor activation and enhancement of postischemic myocardial phosphorylation potential.