title: Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender.
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 [U-(13) C]glucose and [3-(13) C]lactate in hearts preserved in Celsior (Cs) and histidine buffer solution (HBS) for 4 or 6 h and subsequently perfused with a Krebs-Henseleit solution (KH) containing [U-(13) C]glucose and [3-(13) C]lactate. We also assessed gender-specific metabolic modulation in our I/R experimental conditions. Hearts from male and female Wistar rats (6-8 weeks) were subjected to moderate (0-240 min) or prolonged (240-360 min) cold ischemia whilst immersed in Cs and HBS, and perfused for 30 min with KH containing [U-(13) C]glucose and [3-(13) C]lactate. After perfusion, hearts were freeze-clamped 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 6 h of preservation in Cs, lactate origin was mostly from [U-(13) C]glucose in hearts from males and from [3-(13) C]lactate in hearts from females. During the 6 h of organ preservation in HBS, the lactate pool showed a strong contribution from unenriched sources in male hearts and from [U-(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.
authors.affiliation: Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: Rui A
authors.initials: RA
authors.lastname: Carvalho
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002021:Buffers; D002210:Caprylates / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects; D004187:Disaccharides / Q000494:pharmacology; D004573:Electrolytes / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006639:Histidine / Q000494:pharmacology; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D012996:Solutions; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D002021:Buffers; D002210:Caprylates; D002314:Cardioplegic Solutions; C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D012996:Solutions; D019344:Lactic Acid; D008353:Mannitol; D006639:Histidine; D005978:Glutathione; C031492:octanoic acid