Abstract
In conditions of ischemia/reperfusion (I/R), the relative use of all available substrates by the heart has a significant effect on the recovery of the organ. This substrate preference in perfused hearts is influenced by ischemia. We followed the metabolic fate of [Uโ^13^C]glucose and [3โ^13^C]lactate in hearts preserved in Celsior (Cs) and histidine buffer solution (HBS) for 4 or 6โh and subsequently perfused with a KrebsโHenseleit solution (KH) containing [Uโ^13^C]glucose and [3โ^13^C]lactate. We also assessed genderโspecific metabolic modulation in our I/R experimental conditions. Hearts from male and female Wistar rats (6โ8 weeks) were subjected to moderate (0โ240โmin) or prolonged (240โ360โmin) cold ischemia whilst immersed in Cs and HBS, and perfused for 30โmin with KH containing [Uโ^13^C]glucose and [3โ^13^C]lactate. After perfusion, hearts were freezeโclamped and metabolites were extracted for ^13^C NMR isotopomer analysis. In control conditions, there were no differences with regard to lactate origin in hearts from males and females. After 6โh of preservation in Cs, lactate origin was mostly from [Uโ^13^C]glucose in hearts from males and from [3โ^13^C]lactate in hearts from females. During the 6โh of organ preservation in HBS, the lactate pool showed a strong contribution from unenriched sources in male hearts and from [Uโ^13^C]glucose in female hearts. The glutamate C2/C4 ratio was stable or increased in hearts from females after I/R, and the alanine index increased in hearts from both males and females. Octanoate was, as predicted, the preferential substrate during perfusion. Glucose and lactate suffer a distinct metabolic fate in our I/R conditions, which is related to the cardioplegic solution used during organ storage, and the gender. Hearts from females appear to be less sensitive to I/R injury, and heart preservation in HBS proved to be effective in enhancing anaplerosis during perfusion, especially in hearts from females. Copyright ยฉ 2011 John Wiley & Sons, Ltd.