The effects of a purine precursor, AICAriboside (5-aminoimidazole-4-carboxamide riboside), on postischemic recovery of myocardial function and adenine nucleotides have been studied in the isolated blood-perfused cat heart. The isolated hearts received either AICAriboside or saline prior to 60 min of global ischemia and during 60 min of subsequent reperfusion. After 60 min of global ischemia and reperfusion, left ventricular function of the AICAriboside-treated hearts approached preischemic values, whereas contractile function of the saline-treated hearts remained depressed. At 60 min postischemia, recovery of left ventricular developed pressure (LVDP) was 62 +/- 10% for the saline-treated hearts as compared to 93 +/- 8% for the AICAriboside-treated hearts. Left ventricular compliance of the saline-treated hearts was decreased slightly at 60 min postischemia. In contrast, left ventricular compliance was increased in the isolated hearts which received AICAriboside. Myocardial ATP concentrations were decreased significantly at 60 min postischemia in both the saline-treated hearts and in the AICAriboside-treated hearts relative to nonischemic hearts. Similarly, total adenine nucleotides (TAN = ATP + ADP + AMP) were decreased significantly in both the saline-treated hearts and AICAriboside-treated hearts relative to nonischemic hearts. The present study demonstrates that AICAriboside protected globally ischemic hearts from the mechanical dysfunction associated with an ischemic insult but did not restore ATP or the total adenine nucleotide pool of the postischemic myocardium.