Cardioprotective effects of nucleoside transport inhibition in rabbit hearts

Abstract

The cardioprotective effects of a nucleoside transport inhibitor, R75231, were investigated in the isolated rabbit heart. The hearts were subjected to 20 minutes of global normothermic ischemia followed by reperfusion. Before ischemia either solvent (group 1), 5 mumol/L of adenosine (group 2), or 0.64 mg/L R75231 (group 3) was added to the perfusate. Preischemic hemodynamics were not changed by treatment, except for an increase in coronary flow in the adenosine group (126% of control; p less than 0.05). Upon reperfusion, coronary flow was depressed in the controls (72% of the preischemic control values), increased in the adenosine group (113%) and unchanged in the R75231 group (89%). Functional recovery was significantly better in the adenosine group as well as in the R75231 group as compared with the controls (p less than 0.05). Cardiac output was 74% of the preischemic control value in the R75231 group, 67% in the adenosine group, and only 38% in the controls. Analysis of the coronary effluent after reperfusion showed a significant inhibition of rapid release of purines and a reverse of the adenosine/inosine ratio in the R75231 group as compared with the others. We conclude that R75231 has a cardioprotective effect that is probably related to accumulation of endogenous adenosine.