We have previously studied the relation between long-chain fatty acid and pyruvate metabolism in reperfused myocardium and noted a rapid return of fatty acid oxidation to at least preischemic values accompanied by a marked decrease in pyruvate oxidation. The purpose of the present report is to further characterize carbohydrate metabolism during reflow by describing rates of glucose oxidation using [6-14C]glucose. Chddative performance was determinedwith and without preserved fatty acid utilization; the latter condition was effected byoxfenicine, which inhibits palmitoylcarnitine transferase I. In the main protocol, two groups ofworking swine hearts (n=18) were perfused aeroblcaUy for 30 minutes, rendered regionallyischemic (−60 Δ% in anterior descending coronary flow) for 45 minutes, and reperfused atcontrol flows for a final 50 minutes of perfusion. An emulsion of Intralipid with heparin wasadministered systemically throughout the studies to augment serum fatty acids (average fattyacid values, 1.05 ± 0.05 μmol/ml for both groups). Serum glucose was monitored and maintainedat or about 100 rag/dl with additional infusions of glucose as needed. Oxfenicine (33mg/kg) was administered systemically by bolus injection at time 0 and 60 minutes of perfusionin nine animals. Decreased mechanical performance, that is, stunning, during reflow wasevident in both groups (−50 Δ% in regional systolic shortening,p< .0.05 compared with aerobicvalues in the control group, and -32 Δ%,p≤ 0.05 compared with aerobic values in treatedhearts). This stunning was associated with concordant reductions in myocardial oxygenconsumption during recovery (−15 Δ%,p≤ 0.02 for the control group, and -21 Δ%,p≤ 0.01 for the treated group).14CO2production from labeled glucose was strongly suppressed duringpreischemic perfusion in both groups, rose slightly during ischemia, and continued to rise in theoxfenicine group during reperfusion to twice the values measured in control hearts (p≤ 0.01).These responses were contrasted with data from five additional, similarly perfused hearts thatdid not receive Intralipid. Reducing fatty acids twofold In the perfusate caused no majorchanges in glucose oxidation as compared with control hearts. Tissue glycogen was detected inboth aerobic and reperfused myocardium and was unaffected by oxfenicine treatment. Thesedata confirm previous findings and do not support an argument for increased glucose oxidation. Rather, the results support the concept of competitive inhibition of glucose and/or itsintermediates by the preferred use of fatty acids.