SUBSTRATE COMPETITION IN POSTISCHEMIC MYOCARDIUM - EFFECT OF SUBSTRATE AVAILABILITY DURING REPERFUSION ON METABOLIC AND CONTRACTILE RECOVERY IN ISOLATED RAT HEARTS

Normal myocardium can derive energy for contraction and relaxation fro m oxidative metabolism of a variety of substrates. This investigation examined the influence of substrate availability early during reperfus ion on the substrate pattern of oxidative metabolism and recovery of c ontractile function. For this purpose, isovolumically beating isolated rat hearts, perfused retrogradely with erythrocyte-supplemented buffe r containing 0.4 mmol/L palmitate and 11 mmol/L glucose, were subjecte d to 40 minutes of no-flow ischemia. Hearts were reperfused with mediu m containing selected concentrations of palmitate and glucose. The sub strate pattern for oxidative metabolism was determined on the basis of myocardial release of (CO2)-C-14 after equilibration of the hearts du ring the initial 15 minutes of reperfusion with either [1-C-14]palmita te or [U-C-14]glucose. In continuously perfused control hearts, glucos e oxidation was largely inhibited by palmitate. During postischemic re perfusion, oxidation of glucose was increased by 59% (P<.05) and 467% (P<.01) in hearts reperfused after the ischemic period with 11 mmol/L glucose plus 0.4 or 1.2 mmol/L palmitate, respectively. Oxidation of p almitate was concomitantly reduced during reperfusion at low (0.4 mmol /L) but not at high (1.2 mmol/L) palmitate concentration. Compared wit h hearts reperfused with medium containing 0.4 mmol/L, palmitate as so le substrate, hearts reperfused with medium containing 11 mmol/L gluco se with 0.4 mmol/L palmitate exhibited lower left ventricular diastoli c pressure (69+/-5 versus 90+/-3 mm Hg [mean+/-SEM], P<.05), less rele ase of creatine kinase (31+/-5 versus 59+/-7 U/g wet wt, P<.05), and b etter recovery of left ventricular pressure development (26+/-9 versus 6+/-4 mm Hg, P<.05). Omission of palmitate or increasing the palmitat e concentration to 1.2 mmol/L did not significantly alter postischemic myocardial contracture and enzyme release. The findings support the v iew that glucose oxidation early during reperfusion may be crucial for functional recovery. The results further indicate that interaction of substrates of oxidative metabolism is altered in severely injured pos tischemic myocardium. Inhibition of glucose oxidation by fatty acids w as partially reversed during reperfusion.