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

Fatty acid and glucose oxidation rates were measured in isolated rat h earts undergoing hypothermia and rewarming. The hearts were perfused i n the Langendorff mode with Krebs-Henseleit bicarbonate buffer contain ing 11.1 mm glucose plus 0.6 mm albumin-bound oleic acid as energy sub strates. The hearts were stabilized at 37-degrees-C and thereafter coo led 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-degre es-C during the next 30 min. Control hearts were perfused at 37-degree s-C throughout the whole perfusion period. Trace amounts of [C-14]gluc ose or [C-14]oleic acid were included in the perfusate, and the rate o f substrate oxidation was determined on the basis of the radioactive C O2 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 mu mol min-1 g-1 dry wt, respectively (mean +/- SEM). In response to hypo thermia (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 oxidati on 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 es sentially 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 conditi ons. The molar ratio between glucose and fatty acid oxidation was, how ever, significantly (P < 0.05) lower in hypothermic than in normotherm ic hearts. This finding indicates a shift in the metabolism of hypothe rmic hearts towards an even higher preference for fatty acids than tha t observed in normothermic hearts.