SUBSTRATE PREFERENCE OF ISOLATED-PERFUSED RAT HEARTS DURING HYPOTHERMIA AND REWARMING

Fatty acid and glucose oxidation rates were measured in isolated rat hearts undergoing hypothermia and rewarming. The hearts were perfused in the Langendorff mode with Krebs-Henseleit bicarbonate buffer containing 11.1 mm glucose plus 0.6 mm albumin-bound oleic acid as energy substrates. The hearts were stabilized at 37-degrees-C and thereafter cooled progressively to 15-degrees-C over a period of 60 min. The hearts were kept at this temperature for 10 min and then rewarmed to 37-degrees-C during the next 30 min. Control hearts were perfused at 37-degrees-C throughout the whole perfusion period. Trace amounts of [C-14]glucose or [C-14]oleic acid were included in the perfusate, and the rate of substrate oxidation was determined on the basis of the radioactive CO2 production. In normothermic hearts steady state oxidation rates of glucose and oleate were found to be 0.17 +/- 0.01 and 0.51 +/- 0.07 mumol min-1 g-1 dry wt, respectively (mean +/- SEM). In response to hypothermia (15-degrees-C) glucose oxidation was reduced by 76% (from 0.17 +/- 0.01 to 0.04 +/- 0.01 /mumol min-1 g-1 dry wt) and oleate oxidation by 47% (from 0.51 +/- 0.07 to 0.27 +/- 0.02 mumol min-1 g-1 dry wt). Upon rewarming glucose and fatty acid oxidation rates returned to essentially the same values (0.12 +/- 0.02 and 0.45 +/- 0.04 mumol min-1 g-1 dry wt) as those observed under steady state normothermic conditions. The molar ratio between glucose and fatty acid oxidation was, however, significantly (P < 0.05) lower in hypothermic than in normothermic hearts. This finding indicates a shift in the metabolism of hypothermic hearts towards an even higher preference for fatty acids than that observed in normothermic hearts.