The effect of dipyridamole (DYP) on postischemic myocardial function and metabolism was studied using the isolated rabbit heart model. Twenty-one isolated rabbit heart preparations were divided into two groups: KH (control N = 10) were reperfused after 24 min normothermic hyperkalemic arrest with modified Krebs-Henseleit buffer (KH) while DYP (N = 11) were reperfused with KH and 5 X 10(-6) M DYP. Hearts were analyzed for myocardial function (DP, developed pressure, +dp/dt, -dp/dt) and metabolic function (ATP, CrP, ADP, AMP, purines, and lactate levels). Data analysis revealed significant reperfusion depression in DYP myocardial function compared with KH (P less than 0.05): DP (42 +/- 6 vs 89 +/- 7 mm Hg), +dp/dt (390 +/- 21.6 vs 1227 +/- 48.4), and -dp/dt (280 +/- 20.1 vs 677 +/- 19.8). Comparison of DYP to KH metabolic parameters was also significantly different (P less than 0.05): ATP (5.8 +/- 0.7 vs 9.5 +/- 1.4), ADP (2.1 +/- 0.2 vs 3.2 +/- 0.6), CrP (9.6 +/- 0.3 vs 17.2 +/- 1.3). Tissue purines (adenosine and inosine) were significantly elevated (P less than 0.01) in the DYP group, while coronary sinus purines and lactate loss were similar. Thus, the data suggest that DYP, present during postischemic reperfusion, depresses myocardial function by inhibiting adenosine phosphorylation, thereby decreasing the generation of high-energy phosphates without increased substrate loss or ischemia.