Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15°C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by Fluorocarbons at a concentration of 10% (O2 content: 5.5 vol %; group II) or 20% (O2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 ± 5.9% of control) than in group I (59.1 ± 5.4% of control, P < 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 ± 11.21% vs 74.12 ± 3.59%, at 3 min of reperfusion, P < 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate. The observation that the 10% fluorocarbon solution yielded a better recovery than the 20% solution tends to support the concept of an optimal amount of oxygen to be delivered during the early postischemic period to help minimizing reperfusion injury. © 1985.