Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender

NMR Biomed. 2011 Nov;24(9):1029-37. doi: 10.1002/nbm.1640. Epub 2011 Jan 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Buffers
  • Caprylates / pharmacology
  • Cardioplegic Solutions / pharmacology*
  • Citric Acid Cycle / drug effects
  • Disaccharides / pharmacology
  • Electrolytes / pharmacology
  • Female
  • Glutamates / pharmacology
  • Glutathione / pharmacology
  • Heart / drug effects*
  • Histidine / pharmacology
  • In Vitro Techniques
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Mannitol / pharmacology
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology*
  • Perfusion
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Solutions
  • Substrate Specificity


  • Amino Acids
  • Buffers
  • Caprylates
  • Cardioplegic Solutions
  • Celsior
  • Disaccharides
  • Electrolytes
  • Glutamates
  • Solutions
  • Lactic Acid
  • Mannitol
  • Histidine
  • Glutathione
  • octanoic acid