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Impact of lactate in the perfusate on function and metabolic parameters of isolated working rat heart

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Abstract

The goal of this study was to investigate the effect of 1 mM exogenous lactate on cardiac function, and some metabolic parameters, such as glycolysis, glucose oxidation, lactate oxidation, and fatty acid oxidation, in isolated working rat hearts. Hearts from male Sprague-Dawley rats were isolated and perfused with 5 mM glucose, 1.2 mM palmitate, and 100 μU/ml insulin with or without 1 mM lactate. The rates of glycolysis, glucose, lactate, and fatty acid oxidation were determined by supplementing the buffer with radiolabeled substrates. Cardiac function was similar between lactate+ and lactate− hearts. Glycolysis was not affected by 1 mM lactate. The addition of lactate did not alter glucose oxidation rates. Interestingly, palmitate oxidation rates almost doubled when 1 mM lactate was present in the perfusate. This study suggests that subst rate supply to the heart is crucially important when evaluating the data from metabolic studies.

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References

  1. Lopaschuk GD: Advantages and limitations of experimental techniques used to measure cardiac energy metabolism. J Nucl Cardiol 4:316–328, 1997

    Article  PubMed  CAS  Google Scholar 

  2. Barr RL, Lopaschuk GD: Methodology for measuring in vitro/ex vivo cardiac energy metabolism. J Pharmacol Toxicol Methods 43(2):141–152, 2000

    Article  PubMed  CAS  Google Scholar 

  3. Rosier CD, Llyod S, Comte B, Chatham JC: A critical perspective of the use of 13C-isotopomer analysis by GCMS and NMR as applied to cardiac metabolism. Metab Eng 6: 44–58, 2004

    Article  CAS  Google Scholar 

  4. Chatham JC, Bouchard B, Des Rosiers C: A comparison between NMR and GCMS 13C-isotopomer analysis in cardiac metabolism. Mol Cell Biochem 249:105–112, 2003

    Article  PubMed  CAS  Google Scholar 

  5. Stanley WC, Recchia FA, Lopaschuk GD: Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129, 2005

    Article  PubMed  CAS  Google Scholar 

  6. Jeffrey FMH, Diczku V, Sherry AD, Malloy CR: Substrate selection in the isolated working heart: effects of reperfusion, afterload and concentration. Basic Res Cardiol 90: 388–396, 1995

    Article  PubMed  CAS  Google Scholar 

  7. Chatham JC, Forder JR: Relationship between cardiac function and substrate oxidation in hearts of diabetic rats. Am J Physiol 273:H52–H58, 1997

    PubMed  CAS  Google Scholar 

  8. Chatham JC, Gao ZP, Bonen A, Forder JR: Preferential inhibition of lactate oxidation relative to glucose oxidation in the rat heart following diabetes. Cardiovasc Res 43:96–106, 1999

    Article  PubMed  CAS  Google Scholar 

  9. Chatham JC, Gao ZP, Forder JR: Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation. Am J Physiol 277:E342–E351, 1999

    PubMed  CAS  Google Scholar 

  10. Chatham JC, Seymour AM: Cardiac carbohydrate metabolism in Zucker diabetic fatty rats. Cardiovasc Res 55:104–112, 2002

    Article  PubMed  CAS  Google Scholar 

  11. Lloyd SG, Wang P, Zeng H, Chatham JC: Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart. Am J Physiol 287:H351–H362, 2004

    CAS  Google Scholar 

  12. Wang P, Lloyd SG, Zeng H, Bonen A, Chatham JC: Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats. Am J Physiol 288:H2102–H110, 2005

    Article  CAS  Google Scholar 

  13. Wang P, Lloyd SG, Chatham JC: Impact of high glucose/high insulin and dichloroacetate treatment on carbohydrate oxidation and functional recovery after low-flow ischemia and reperfusion in the isolated perfused rat heart. Circulation 111:2066–2072, 2005

    Article  PubMed  CAS  Google Scholar 

  14. Lopaschuk GD, Collins-Nakai RL, Itoi T: Developmental changes in energy substrate use by the heart. Cardiovasc Res 26:1172–1180, 1992

    Article  PubMed  CAS  Google Scholar 

  15. Onay-Besikci A: Regulation of cardiac energy metabolism in newborn. Mol Cell Biochem, in press

  16. Medina JM: The role of lactate as an energy substrate for the brain during the early neonatal period. Biol Neonate 48:237–244, 1985

    Article  PubMed  CAS  Google Scholar 

  17. Mazer CD, Stanley WC, Hickey RF, Neese RA, Cason BA, Demas KA, Wisneski JA, Gertz EW: Myocardial metabolism during hypoxia: maintained lactate oxidation during increased glycolysis. Metabolism 39:913–918, 1990

    Article  PubMed  CAS  Google Scholar 

  18. Connolly CC, Stevenson RW, Neal DW, Wasserman DH, Cherrington AD: The effects of lactate loading on alanine and glucose metabolism in the conscious dog. Metabolism 42:154–161, 1993

    Article  PubMed  CAS  Google Scholar 

  19. Large V, Soloviev M, Brunengraber H, Beylot M: Lactate and pyruvate isotopic enrichments in plasma and tissues of postabsorptive and starved rats. Am J Physiol 268:E880–E888, 1995

    PubMed  CAS  Google Scholar 

  20. Lopaschuk GD, Spafford MA, Marsh DR: Glycolysis is predominant source of myocardial ATP production immediately after birth. Am J Physiol 261:H1698–H1705, 1991

    PubMed  CAS  Google Scholar 

  21. Werner JC, Sicard RE: Lactate metabolism of isolated, perfused fetal, and newborn pig hearts. Pediatr Res 22:552–556, 1987

    PubMed  CAS  Google Scholar 

  22. Bartelds B, Knoester H, Smid GB, Takens J, Visser GH, Penninga L, van der Leij FR, Beaufort-Krol GC, Zijlstra WG, Heymans HS, Kuipers JR: Perinatal changes in myocardial metabolism in lambs. Circulation 102: 926–931, 2000

    PubMed  CAS  Google Scholar 

  23. Bartelds B, Knoester H, Beaufort-Krol GC, Smid GB, Takens J, Zijlstra WG, Heymans HS, Kuipers JR: Myocardial lactate metabolism in fetal and newborn lambs. Circulation 99:1892–1897, 1999

    PubMed  CAS  Google Scholar 

  24. Bartelds B, Gratama JW, Knoester H, Takens J, Smid GB, Aarnoudse JG, Heymans HS, Kuipers JR: Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs.Am J Physiol 274:H1962–H1969, 1998

    PubMed  CAS  Google Scholar 

  25. Lloyd S, Brocks C, Chatham JC: Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart. Am J Physiol 285:H163–172, 2003

    CAS  Google Scholar 

  26. Schönekess BO. Competition between lactate and fatty acids as sources of ATP in the isolated working rat heart. J Mol Cell Cardiol 29:2725–2733, 1997

    Article  PubMed  Google Scholar 

  27. Ferdinandy P, Panas D, Schulz R. Peroxynitrite contributes to spontaneous loss of cardiac efficiency in isolated working rat hearts. Am J Physiol 276:H1861–H1867, 1999

    PubMed  CAS  Google Scholar 

  28. Lopaschuk GD, Collins-Nakai R, Olley PM, Montague TJ, McNeil G, Gayle M, Penkoske P, Finegan BA. Plasma fatty acid levels in infants and adults after myocardial ischemia. Am Heart J 128:61–67, 1994

    Article  PubMed  CAS  Google Scholar 

  29. Atkinson LL, Fischer MA, Lopaschuk GD: Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J Biol Chem 277:29424–29430, 2002

    Article  PubMed  CAS  Google Scholar 

  30. Longnus SL, Wambolt RB, Barr RL, Lopaschuk GD, Allard MF: Regulation of myocardial fatty acid oxidation by substrate supply. Am J Physiol 281:H1561–H1567, 2001

    CAS  Google Scholar 

  31. Taniguchi M, Wilson C, Hunter CA, Pehowich DJ, Clanachan AS, Lopaschuk GD: Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak. Am J Physiol 280:H1762–H1769, 2001

    CAS  Google Scholar 

  32. McCormack JG, Barr RL, Wolff AA, Lopaschuk GD: Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation 93:135–142, 1996

    PubMed  CAS  Google Scholar 

  33. Kudo N, Barr AJ, Barr RL, Desai S, Lopaschuk GD: High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5’-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270:17513–17520, 1995

    Article  PubMed  CAS  Google Scholar 

  34. Saddik M, Gamble J, Witters LA, Lopaschuk GD: Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem 268:25836–25845, 1993

    PubMed  CAS  Google Scholar 

  35. Broderick TL, Quinney HA, Lopaschuk GD: Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart. J Biol Chem 267:3758–3763, 1992

    PubMed  CAS  Google Scholar 

  36. Lopaschuk GD, Spafford MA, Davies NJ, Wall SR: Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66:546–553, 1990

    PubMed  CAS  Google Scholar 

  37. Wambolt RB, Lopaschuk GD, Brownsey RW, Allard MF: Dichloroacetate improves postischemic function of hypertrophied rat hearts. J Am Coll Cardiol 36:1378–1385, 2000

    Article  PubMed  CAS  Google Scholar 

  38. Halestrap AP, Price NT: The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343:281–299, 1999

    Article  PubMed  CAS  Google Scholar 

  39. McClelland GB, Khanna S, Gonzalez GF, Butz CE, Brooks GA: Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system? Biochem Biophys Res Commun 304:130–135, 2003

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The author would like to thank Dr. Gary D. Lopaschuk at University of Alberta for providing the laboratory facilities and his helpful suggestions.

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  1. Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan 06100, Ankara, Turkey

    Arzu Onay-Besikci

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  1. Arzu Onay-Besikci
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Correspondence to Arzu Onay-Besikci.

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Onay-Besikci, A. Impact of lactate in the perfusate on function and metabolic parameters of isolated working rat heart. Mol Cell Biochem 296, 121–127 (2007). https://doi.org/10.1007/s11010-006-9305-5

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  • DOI: https://doi.org/10.1007/s11010-006-9305-5

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