Skip to main content
SpringerLink
Log in

Substrate dependence of the postischemic cardiomyocyte recovery: Dissociation between functional, metabolic and injury markers

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Defining the substrate that influences the most favourably the myocardial post-ischemic recovery is subject of debates, due to dissociation between functional and biochemical benefits. Hence, we studied the effects of either glucose or different fatty acids on the functional and metabolic recovery of post-ischemic cardiomyocytes in a substrate-free hypoxia model of simulated ischemia-reperfusion. Rat cardiomyocytes were submitted to a 2.5 h simulated ischemia followed by a 2 h reoxygenation without substrate (control), or with either glucose, octanoic acid, oleic acid, or elaidic acid. During simulated ischemia, electromechanical function gradually disappeared while the cellular viability and mitochondrial function declined. During control simulated reperfusion, cardiomyocytes recovered near normal function but a significant reduction in the action potential amplitude and rate persisted. The addition of glucose or oleic acid during simulated reperfusion promoted a faster, better and sustain functional recovery. Amongst the fatty acids, the functional recovery was slower with elaidic and octanoic acids as compared with oleic acid. The mitochondrial function was better improved during simulated reperfusion with glucose than with the tested fatty acids, among which elaidic acid was the less unfavourable. Paradoxically, the addition of whichever substrate during simulated reperfusion tended to worsen the cellular viability. Thus, cardiomyocytes recovery strongly relies on the characteristics of the substrate supplied at the onset of simulated reperfusion: glucidic or lipidic nature, chain-length, insaturation degree. Moreover, these data suggest that defining the appropriateness of a given substrate for the post-ischemic cardiomyocyte recovery is closely related to the functional and the biological endpoints in consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AP:

action potential amplitude

APD40 and APD80:

action potential duration at 40 and 80% of repolarization

APR:

action potential rate

CD20:

contraction duration at 20% relaxation

CD80:

contraction duration at 80% relaxation

Cmax:

relaxation time from 20% to 80% relaxation

LDH:

lactate dehydrogenase

MTT:

3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

tC80:

time to peak contraction

References

  1. Opie LH: The Heart (Physiology Metabolism), 2nd edn., Raven Press, New York, 1991, pp. 18–26

    Google Scholar 

  2. Hearse DJ, Humphrey SM, Bullock GR: The oxygen paradox and the calcium paradox; two facets of the same problem? J Mol Cell Cardiol 13: 265–282, 1978

    Google Scholar 

  3. Piper HM, Garciadorado D, Ovize M: A fresh look at reperfusion injury. Cardiovasc Res 38: 291–300, 1998

    Article  CAS  PubMed  Google Scholar 

  4. Opie LH, Sack MN: Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning. J Mol Cell Cardiol 34: 1077–1089, 2002

    Article  CAS  PubMed  Google Scholar 

  5. Stanley WC, Lopaschuk GD, Hall JL, Mccormack JG: Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions – potential for pharmacological interventions. Cardiovasc Res 33: 243–257, 1997

    Article  CAS  PubMed  Google Scholar 

  6. Dyck JR, Cheng JF, Stanley WC, Barr R, Chandler MP, Brown S, Wallace D, Arrhenius T, Harmon C, Yang G, Nadzan AM, Lopaschuk GD: Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res 94: e78–84, 2004

    Article  CAS  PubMed  Google Scholar 

  7. Neely JR, Grotyohann LE: Role of glycolytic products in damage to ischemic myocardium. Circ Res 55: 816–824, 1984

    CAS  PubMed  Google Scholar 

  8. Tani M, Shinmura K, Ebihara Y, Asakura Y: Inhibition of glycolysis or increased perfusate H+ buffering capacity, but not their combination, attenuates myocardial stunning. Cardiovasc Res 27: 1645–1650, 1993

    CAS  PubMed  Google Scholar 

  9. Tran L, Kucera P, Deribaupierre Y, Rochat AC, Raddatz E: Glucose is arrhythmogenic in the anoxic-reoxygenated embryonic chick heart. Pediatr Res 39: 766–773, 1996

    CAS  PubMed  Google Scholar 

  10. Van de Velde M, DeWolff M, Leather HA, Wouters PF: Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res 48: 129–137, 2000

    Article  CAS  PubMed  Google Scholar 

  11. Löster H, Punzel M: Effects of L-carnitine on mechanical recovery of isolated rat hearts in relation to the perfusion with glucose and palmitate. Mol Cell Biochem 185: 65–75, 1998

    Article  PubMed  Google Scholar 

  12. Kehrer J, Park Y, Sies H: Energy dependence of enzymes release from hypoxic isolated perfused rat heart tissues. J Appl Physiol 65: 1855–1860, 1988

    CAS  PubMed  Google Scholar 

  13. Yamane Y, Ishide N, Kagaya Y, Takeyama D, Shiba N, Chida M, Nozaki T, Takahashi T, Ido T, Shirato K: Heterogeneous fatty acid uptake early after reperfusion in rat hearts. Am J Physiol 43: H923–H929, 1998

    Google Scholar 

  14. Tirosh R, Mishor T, Pinson A: Glucose is essential for the initiation of fatty acid oxidation in ATP-depleted cultured ventricular myocytes. Mol Cell Biochem 162: 159–163, 1996

    Article  CAS  PubMed  Google Scholar 

  15. Schjott, J, Bakoy OE, Jones RA, Southon T, Jynge P: Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by P-31 NMR spectroscopy: Dissociation between metabolic and functional recovery? Scand J Clin Lab Invest 55: 67–78, 1995

    CAS  PubMed  Google Scholar 

  16. Athias P, Grynberg A: Electrophysiological studies on heart cells in culture. In: A. Pinson (eds.) The Heart Cells in Culture, Vol. 1. CRC Press, Boca Raton, USA, pp 125–158, 1987

    Google Scholar 

  17. Grynberg A, Athias P, Degois M: Effect of change in growth environment on cultured myocardial cells investigated in a standardized medium. In vitro Cell Dev Biol 22: 44–50, 1986

    CAS  Google Scholar 

  18. Fantini E, Athias P, Courtois M, Khatami S, Grynberg A, Degois M: Oxygen and substrate deprivation on isolated rat cardiac myocytes: Temporal relationship between electromechanical and biochemical consequences. Can J Physiol Pharmacol 68: 1148–1156, 1990

    CAS  PubMed  Google Scholar 

  19. Fantini E, Athias P, Courtois M, Grynberg A: A simple gas-flow chamber for cultured cell electrophysiology in a controlled atmosphere. Eur J Physiol 409: 632–634, 1987

    Article  CAS  Google Scholar 

  20. Tissier C, Bes S, Vandroux D, Fantini E, Rochette L, Athias P: Specific electromechanicals responses to individual and combined components of ischemia. Can J Physiol Pharmacol 80: 1–13, 2002

    Article  PubMed  Google Scholar 

  21. Grynberg A, Fantini E, Athias P, Degois M, Guenot L, Courtois M, Khatami S: Modification of the n-6/n-3 fatty acid ratio in the phospholipids of rat ventricular myocytes in culture by use of synthetic media; functional and biochemical consequences in normoxic and hypoxic conditions. J Mol Cell Cardiol 20: 863–874, 1988

    CAS  PubMed  Google Scholar 

  22. Athias, P, Groz B, Surville JM, Klepping J: Simultaneous record of mechanical and electrical activities of rat heart cells in culture. Biol Cell 37: 131–136, 1980

    Google Scholar 

  23. Gomez LA, Alekseev AE, Aleksandrova LA, Brady PA, Terzic A: Use of MTT assay in adult ventricular myocytes to assess viability: Effects of adenosine and potassium on cellular survival. J Mol Cell Cardiol 29: 1255–1266, 1997

    Article  CAS  PubMed  Google Scholar 

  24. Chevalier A, Demaison L, Grynberg A, Athias P: Influence of the phospholipid polyunsaturated fatty acid composition on some metabolic disorders induced in rat cardiomyocytes by hypoxia and reoxygenation. J Mol Cell Cardiol 22: 1177–1186, 1990

    Article  CAS  PubMed  Google Scholar 

  25. Reimer KA, Tanaka M, Murry CE, Richard VJ, Jennings RB: Evaluation of free radical injury in myocardium. Toxicol Pathol 18: 470–480, 1990

    CAS  PubMed  Google Scholar 

  26. Durot I, Maupoil V, Ponsard B, Cordelet C, Vergely-Vandriesse C, Rochette L, Athias P: Oxidative injury of isolated cardiomyocytes: Dependence on free radical species. Free Radic Biol Med 29: 846–857, 2000

    Article  CAS  PubMed  Google Scholar 

  27. Apstein CS: Increased glycolytic substrate protection improves ischemic cardiac dysfunction and reduces injury. Am Heart J 139: 107–114, 2000

    Article  Google Scholar 

  28. Diaz R, Paolasso A, Piegas LS, Tajer CD, Moreno MG, Corvalan R, Isea JE, Romero G: Metabolic modulation of acute myocardial infarction: The ECLA glucose-insulin-potassium pilot trial. Circulation 98: 2227–2234, 1998

    CAS  PubMed  Google Scholar 

  29. Lopaschuk GD, Belke DD, Gamble J, Itoi T, Schonekess BO: Regulation of fatty acid oxidation in the mammalian heart in health an disease. Biochim Biophys Acta 1213: 263–276, 1994

    CAS  PubMed  Google Scholar 

  30. Oliver MF, Opie LH: Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet 343: 155–158, 1994

    Article  CAS  PubMed  Google Scholar 

  31. Liedtke AJ, Demaison L, Eggleston AM, Cohen LM, Nellis SH: Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium. Circ Res 62: 535–542, 1988

    CAS  PubMed  Google Scholar 

  32. Theroux P: Protection of the myocardial cell during ischemia. Am J Cardiol 83: 3–9, 1999

    Article  Google Scholar 

  33. Aasum, E, Hafstad A D, Larsen TS: Changes in substrate metabolism in isolated mouse hearts following ischemia-reperfusion. Mol Cell Biochem 249: 97–103, 2003

    Article  CAS  PubMed  Google Scholar 

  34. Van de Velde M, DeWolff M, Leather HA, Wouters PF: Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res 48: 129–137, 2000

    Article  CAS  PubMed  Google Scholar 

  35. Hart BJ, Bian XM, Mallet RT, Downey HF: Hyperlipidemia with hypoglycemia reduces myocardial oxygen utilization efficiency but not contractile function during coronary hypoperfusion. J Mol Cell Cardiol 32: 1539–1552, 2000

    Article  CAS  PubMed  Google Scholar 

  36. Montessuit C, Papageorgioou I, Tardy-Cantalupi I, Rosenblatt-Velin N, Lerch R: Post-ischemic recovery of heart metabolism and function: Role of mitochondrial fatty acid transfer. J Appl Physiol 89: 111–119, 2000

    CAS  PubMed  Google Scholar 

  37. Lewandowski ED, Kudej RK, White LT, ODonnell JM, Vatner SF: Mitochondrial preference for short chain fatty acid oxidation during coronary artery constriction. Circulation 105: 367–372, 2002

    Article  CAS  PubMed  Google Scholar 

  38. Zanotti G: Muscle fatty acid-binding protein. Biochim Biophys Acta 1441: 94–105, 1999

    CAS  PubMed  Google Scholar 

  39. Lichtenstein AH, Schwab US: Relationship of dietary fat to glucose metabolism. Atherosclerosis 150: 227–243, 2000

    CAS  PubMed  Google Scholar 

  40. De Vries JE, Vork MM, Roemen THM, Dejong YF, Cleutjens JPM, Van der Vusse GJ, Vanbilsen M: Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J Lipid Res 38: 1384–1394, 1997

    CAS  PubMed  Google Scholar 

  41. Stender S, Dyerberg J: Influence of trans fatty acids on health. Ann Nutr Metab 48: 61–66, 2004

    CAS  PubMed  Google Scholar 

  42. Frelin C: Glucose and palmitate metabolism by beating rat heart cells in culture. Path Biol 27: 45–50, 1979

    CAS  Google Scholar 

  43. Schjott J, Bakoy OE, Jones RA, Southon T, Jynge P: Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by P-31 NMR spectroscopy: Dissociation between metabolic and functional recovery? Scand J Clin Lab Invest 55: 67–78, 1995

    CAS  PubMed  Google Scholar 

  44. McCarty MF: A shift in myocardial substrate, improved endothelial function, and diminished sympathetic activity may contribute to the anti-anginal impact of very-low-fat diets. Med Hypothesis 62: 62–71, 2004

    CAS  Google Scholar 

  45. Van Bilsen M, Smeets PJ, Gilde AJ, Van der Vusse GJ: Metabolic remodelling of the failing heart: The cardiac burn-out syndrome? Cardiovasc Res 61: 218–226, 2004

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Cardiovascular Physiopathology and Pharmacology, IFR n∘ 100, Institute of Cardiovascular Research, University Hospital Center, Dijon, France

    Cindy Tissier, David Vandroux, Lisa Devillard, Amandine Brochot, Daniel Moreau, Luc Rochette & Pierre Athias

  2. Laboratory of Experimental Cardiovascular Physiopathology and Pharmacology (Institute of Cardiovascular Research), University Hospital Center, 2, bd Mal de Lattre de Tassigny, 21034, Dijon, Cedex, France

    Pierre Athias

Authors
  1. Cindy Tissier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Vandroux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lisa Devillard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amandine Brochot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Moreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luc Rochette
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pierre Athias
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre Athias.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tissier, C., Vandroux, D., Devillard, L. et al. Substrate dependence of the postischemic cardiomyocyte recovery: Dissociation between functional, metabolic and injury markers. Mol Cell Biochem 273, 43–55 (2005). https://doi.org/10.1007/s11010-005-7375-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-7375-4

Keywords

Search

Navigation