Skip to main content
SpringerLink
Log in

Importance of glycolytically produced ATP for the integrity of the threatened myocardial cell

  • Chapter
Pathophysiology of Severe Ischemic Myocardial Injury

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 104))

Summary

The hypothesis that glycolytically produced ATP has a special role in the preservation of myocardial cells is critically examined. Considerable indirect evidence supports this proposal, although the electrophysiological data remain controversial and capable of different interpretations. Thus far the most convincing evidence favoring the concept of compartmentation comes from data relating rates of glycolytic flux to enzyme release from the isolated heart or from isolated myocytes and from the regulation of the onset of ischemic contracture. More direct evidence has now been obtained in isolated cardiac myocytes. The hypothesis formed the basis of a metabolically orientated approach towards decreasing severity of myocardial ischemic injury. Nonetheless, until analytical methods become available for the specific measurement of a membrane-related pool of ATP, the hypothesis will be supported by indirect rather than direct evidence.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sodi-Pallares D, Testelli MR, Fishleder BR, et al. (1962) Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. A preliminary clinical report. Am J Cardiol 9: 166–181

    Article  PubMed  CAS  Google Scholar 

  2. Owen P, Thomas M, Opie LH (1969) Relative changes in free fatty acid and glucose utilisation by ischemic myocardium after coronary artery occlusion. Lancet i: 1187–1190

    Article  Google Scholar 

  3. Opie LH (1970) The glucose hypothesis: Relation to acute myocardial ischemia. J Mol Cell Cardiol 1: 107–115

    Article  Google Scholar 

  4. Bricknell OL, Opie LH (1978) Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion. Circ Res 43: 102–115

    PubMed  CAS  Google Scholar 

  5. Anderson GL, Morris RG (1978) Role of glycolysis in the relaxation process in mammalian cardiac muscle: Comparison of the influence of glucose and 2-deoxyglucose on maintenance of resting tension. Life Sci 23: 23–32

    Article  PubMed  CAS  Google Scholar 

  6. Opie LH (1989) Hypothesis: Glycolytic rates control cell viability in ischemia. J Appl Cardiol, in press

    Google Scholar 

  7. Achs MJ, Garfinkel D (1977) Computer stimulation of energy metabolism in anoxic perfused rat heart. Am J Physiol 232: R164–R174

    PubMed  CAS  Google Scholar 

  8. Opie LH (1971/72) Substrate utilization and glycolysis in the heart. Cardiology 56: 2–21

    Article  PubMed  CAS  Google Scholar 

  9. Newsholme EA (1971) The regulation of phosphofructokinase in muscle. Cardiology 56: 22–34

    Article  PubMed  CAS  Google Scholar 

  10. Opie LH (1968) Metabolism of the heart. I. Metabolism of glucose, glycogen, free fatty acids and ketone bodies. Am Heart J 76: 685–698

    Article  PubMed  CAS  Google Scholar 

  11. Opie LH (1975) Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction. Relation to myocardial ischemia and infarct size. Am J Cardiol 36: 938–953

    Article  PubMed  CAS  Google Scholar 

  12. Opie LH (1983) High energy phosphate compounds. In: Drake-Holland AJ, Noble MIM (eds) Cardiac Metabolism. John Wiley and Sons Ltd, 279–307

    Google Scholar 

  13. Prasad K, MacLeod DP (1969) Influence of glucose on the transmembrane action potential of guinea-pig papillary muscle. Circulation 24: 939–950

    CAS  Google Scholar 

  14. Eisenberg G, Vereecke J, van der Heyden G, Carmeleit E (1983) The shortening of the action potential by DNP in guinea-pig ventricular myocytes is mediated by an increase of a time-independent K conductance. Pflugers Arch 397: 251–259

    Article  Google Scholar 

  15. Hayashi H, Watanabe T, McDonald TF (1987) Action potential duration in ventricular muscle during selective metabolic block. Am J Physiol 253: H373–H379

    PubMed  CAS  Google Scholar 

  16. Opie LH, Tuschmidt R, Bricknell OL, et al. (1980) Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart. J Physiol (Paris) 76: 821–829

    CAS  Google Scholar 

  17. Cheneval JP, Hyde A, Blondel B, et al. (1972) Heart cells in culture. Metabolism, action potential and transmembrane ionic movements. J Physiol (Paris) 64: 413–430

    CAS  Google Scholar 

  18. Noma A, Shibasaki T (1985) Membrane current through adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol (Lond) 363: 463–480

    CAS  Google Scholar 

  19. Kantor P, Coetzee WA, Carmeleit E, et al. (1989) Reduction in ischemic K+ loss and arrhythmias: The effect of the sulfonylurea, glibenclamide. Circ Res, in press

    Google Scholar 

  20. Dunne MJ, Petersen OH (1986a) Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin secreting cell line. FEBS Let 208: 59–62

    Article  CAS  Google Scholar 

  21. Dunne MJ, Petersen OH (1986b) GTP and GDP activation of K+ channels that can be inhibited by ATP. Pflugers Arch 407: 564–565

    Article  PubMed  CAS  Google Scholar 

  22. Weiss JN, Lamp ST (1987) Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes. Science 238: 67–69

    Article  PubMed  CAS  Google Scholar 

  23. De Leiris J, Lubbe WF, Opie LH (1975) Effects of free fatty acid and glucose on enzyme release in experimental myocardial infarction. Nature 153: 746–747

    Article  Google Scholar 

  24. Opie LH, Bricknell OL (1979) Role of glycolytic flux in effect of glucose in decreasing fatty-acid induced release of lactate dehydrogenase from isolated coronary ligated rat heart. Cardiovasc Res 13: 693–702

    Article  PubMed  CAS  Google Scholar 

  25. Higgins TJC, Bailey PJ, Allsopp D (1981) The influence of ATP depletion on the action of phospholipase C on cardiac myocyte membrane phospholids. J Mol Cell Cardiol 13: 1027–1030

    Article  PubMed  CAS  Google Scholar 

  26. Higgins TJC, Allsopp D, Bailey PJ, D’Souza EDA (1981) The relationship between glycolysis, fatty acid metabolism and membrane integrity in neonatal myocytes. J Mol Cell Cardiol 13: 599–615

    Article  PubMed  CAS  Google Scholar 

  27. Gudbjarnason S, Mathes R, Ravens KG (1970) Functional compartmentation of ATP and creatine phosphate in heart muscle. J Mol Cell Cardiol 1: 325–339

    Article  PubMed  CAS  Google Scholar 

  28. Bricknell OL, Daries PS, Opie LH (1981) A relationship between adenosine triphosphate, glycolysis and ischemic contracture in the isolated rat heart. J Mol Cell Cardiol 13: 941–945

    Article  PubMed  CAS  Google Scholar 

  29. Katz AM, Tada M (1977) The’ stone heart’ and other challenges to the biochemist. Am J Cardiol 39: 1073–1077

    Article  PubMed  CAS  Google Scholar 

  30. Hearse DJ, Garlick PB, Humphrey SM (1977) Ischemic contracture of the myocardium: mechanism and prevention. Am J Cardiol 39: 986–993

    Article  PubMed  CAS  Google Scholar 

  31. Lipasti JA, Nevalainen TJ, Alanen KA, Tolvanen MA (1984) Anaerobic glycolysis and the development of ischemic contracture in isolated rat heart. Cardiovasc Res 18: 145–148

    Article  PubMed  CAS  Google Scholar 

  32. Allen DG, Morris PG, Orchard CH, Pirolo JS (1985) A nuclear magnetic resonance study of metabolism in the ferret heart during hypoxia and inhibition of glycolysis. J Physiol 361: 185–204

    PubMed  CAS  Google Scholar 

  33. Bittl JA, Balschi J, Ingwall JS (1987) Contractile failure and high-energy phosphate turnover during hypoxia: 31P-NMR surface coil studies in living rat. Circ Res 60: 871–878

    PubMed  CAS  Google Scholar 

  34. Owen P, Dennis SC, Opie LH (1989) Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. Circ Res, in press

    Google Scholar 

  35. Bing OHL, Fishbein MC (1979) Mechanical and structural correlates of contracture induced by metabolic blockade in cardiac muscle from the rat. Circ Res 45: 298–308

    PubMed  CAS  Google Scholar 

  36. Kubier W, Spieckermann PG (1970) Regulation of glycolysis in the ischemic and the anoxic myocardium. J Mol Cell Cardiol 1: 351–357

    Article  Google Scholar 

  37. Laiho KU, Trump BF (1975) Studies on the pathogenesis of cell injury — effects of inhibitors of metabolism and membrane function on the mitochondria of Ehrlich ascites tumor cells. Lab Invest 32: 163–182

    PubMed  CAS  Google Scholar 

  38. Trump BF, Mergner WJ, Kahng MW, et al. (1976) Studies on the subcellular pathophysiology of ischemia. Circulation 53 (Suppl 1): 17–26

    Google Scholar 

  39. Jennings RB, Hawkins HK, Lowe JE, et al. (1978) Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. Am J Pathol 92: 187–207

    PubMed  CAS  Google Scholar 

  40. Lowe JE, Jennings RB, Reimar KA (1979) Cardiac rigor mortis in dogs. J Mol Cell Cardiol 11: 1017–1031

    Article  PubMed  CAS  Google Scholar 

  41. Schaper J, Mulch J, Winkler B, Schaper W (1979) Ultrastructural, functional, and biochemical criteria for estimation of reversibility of ischemic injury: a study on the effects of global ischemia on the isolated dog heart. J Mol Cell Cardiol 11: 521–541

    Article  PubMed  CAS  Google Scholar 

  42. Haworth RA, Hunter DR, Berkoff HA (1981) Contracture in isolated adult rat heart cells. Role of Ca2+, ATP and compartmentation. Circ Res 49: 1119–1128

    PubMed  CAS  Google Scholar 

  43. Neely JR, Grotyohann LW (1984) Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 55: 816–824

    PubMed  CAS  Google Scholar 

  44. Lagerstrom CF, Walker WE, Taegtmeyer H (1988) Failure of glycogen depletion to improve left ventricular function of the rabbit heart after hypothermic ischemic arrest. Circ Res 63: 81–86

    PubMed  CAS  Google Scholar 

  45. Rose A, Opie LH, Bricknell O (1976) Evaluation of histologic criteria of early experimental myocardial infarction. Comparison with biochemical and electrocardiographic parameters. Arch Pathol 100: 516–571

    CAS  Google Scholar 

  46. Ferrari R, Curello S, Ceconi C (1986) Glucose and FFA as myocardial substrate during ischemia: Effects on glutathione status (Abstract). J Mol Cell Cardiol 18 (Suppl 1): 108

    Google Scholar 

  47. Apstein CS, Gravino FN, Haudenschild CC (1983) Determinants of a protective effect of glucose and insulin on the ischemic myocardium. Circ Res 52: 515–526

    PubMed  CAS  Google Scholar 

  48. Opie LH, Owen EP, Dennis SC (1985) Glycolysis prevents ischemic contracture (Abstract). Circulation 72 (Suppl III): 349

    Google Scholar 

  49. Allen DG, Lee JA, Smith GL (1988) The effects of simulated ischaemia on intracellular calcium and tension in isolated ferret ventricular muscle. J Physiol 400: 91P-92P

    Google Scholar 

  50. Armiger LC, Gavin JB, Herdson PB (1974) Mitochondrial changes in dog myocardium induced by neutral lactate in vivo. Lab Invest 31: 29–33

    PubMed  CAS  Google Scholar 

  51. Sochor H, Schwaiger M, Schelbert HR, et al. (1985) Assessment of tissue viability in reperfused canine myocardium by a multiple radiotracer technique (Abstract). J Am Coll Cardiol 5: 451

    Google Scholar 

  52. Sochor H, Schwaiger M, Schelbert HR, et al. (1987) Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium. Am Heart J 114: 1066–1077

    Article  PubMed  CAS  Google Scholar 

  53. Melin JA, Wijns W, Keyeux A, et al. (1988) Assessment of thallium-201 redistribution versus glucose uptake as predictors of viability after coronary occlusion and reperfusion. Circulation 77: 927–934

    Article  PubMed  CAS  Google Scholar 

  54. Tillisch J, Brunken R, Marshall R, et al. (1986) Reversibility of cardiac wall-motion abnormalities predicted by positron tomography. New Engl J Med 314: 884–888

    Article  PubMed  CAS  Google Scholar 

  55. Marshall RC, Tillisch JH, Phelps ME, et al. (1983) Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia. Circulation 67: 766–778

    Article  PubMed  CAS  Google Scholar 

  56. Brunken R, Tillisch J, Schwaiger M, et al. (1986) Regional perfusion, glucose metabolism and wall motion in patients with chronic electrocardiographic Q-wave infarctions: evidence for peristence of viable tissue in some infarct regions by positron emission tomography. Circulation 73: 951–963

    Article  PubMed  CAS  Google Scholar 

  57. Opie LH, Thomas M (1976) Propranolol and experimental myocardial infarction: substrate effects. Postgrad Med J 52 (Suppl 4): 124–132

    PubMed  Google Scholar 

  58. Dalby AJ, Bricknell OL, Opie LH (1981) Effect of glucose-insulin-potassium infusions on epicardial ECG changes and on myocardial metabolic changes after coronary artery ligation in dogs. Cardiovasc Res 15: 588–598

    Article  PubMed  CAS  Google Scholar 

  59. Opie LH, Owen P (1976) Effect of glucose-insulin-potassium infusions on arteriovenous differences of glucose and of free fatty acids and on tissue metabolic changes in dogs with developing myocardial infarction. Am J Cardiol 38: 310–321

    Article  PubMed  CAS  Google Scholar 

  60. Liedtke AJ, Hughes HC, Neely JR (1976);) Effects of excess glucose and insulin on glycolytic metabolism during experimental myocardial ischemia. Am J Cardiol 38: 17–27

    Article  PubMed  CAS  Google Scholar 

  61. Opie LH (1988) Sympathetic stimulation of ischemic myocardium: Role of plasma free fatty acids and potassium. J Cardiovasc Pharmacol 12 (Suppl 1): S31–S38

    Article  PubMed  CAS  Google Scholar 

  62. Hoekenga DE, Brainard JR, Hutson JY (1988) Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study. Circ Res 62: 1065–1074

    PubMed  CAS  Google Scholar 

  63. Liedtke AJ, Nellis SH, Whitesell LF (1982) Effects of regional ischemia on metabolic function in adjacent aerobic myocardium. J Mol Cell Cardiol 14: 195–205

    Article  PubMed  CAS  Google Scholar 

  64. Rovetto MJ, Whitmer JT, Neely JR (1973) Comparison of effects of anoxia and whole heart ischemia on carbohydrate utilization in isolated working rat hearts. Circ Res 22: 699–711

    Google Scholar 

  65. Neely JR, Liedtke AJ, Whitmer JT, et al. (1975) Relationship between coronary flow and adenosine triphosphate production from glycolysis and oxidative metabolism. In: Roy PR, Harris P (eds) Recent Advances in Studies on Cardiac Structure and Metabolism. Baltimore: University Park Press, 301–321

    Google Scholar 

  66. Sinclair-Smith B, Opie LH (1978) Effect of diabetic ketosis on enzyme release from isolated perfused rat hearts with experimental myocardial infarction. J Mol Med 10: 221–234

    CAS  Google Scholar 

  67. De Leiris J, Feuvray D (1977) Ischaemia-induced damage in the working rat heart preparation. The effect of perfusate substrate composition upon subendocardial ultrastructure of the ischaemic left ventricular wall. J Mol Cell Cardiol 9: 365–373

    Article  PubMed  Google Scholar 

  68. Wissner SB (1974) The effect of excess lactate upon the excitability of the sheep Purkinje fiber. J Electrocardiol 7: 17–26

    Article  PubMed  CAS  Google Scholar 

  69. Regan, TJ, Effros RM, Haider B, et al. (1976) Myocardial ischaemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition. Am J Cardiol 37: 501–507

    Article  PubMed  CAS  Google Scholar 

  70. Maroko PR, Kjekshus JK, Sobel BE, et al. (1971) Factors influencing infarct size following experimental coronary artery occlusions. Circulation 43: 67–82

    PubMed  CAS  Google Scholar 

  71. Maroko PR, Libby P, Sobel BE, et al. (1972) Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation 45: 1160–1175

    PubMed  CAS  Google Scholar 

  72. Oliver MF, Rowe MJ, Luxton MR, et al. (1976) Effect of reducing circulating free fatty acids on ventricular arrhythmias during myocardial infarction and on ST-segment depression during exercise-induced ischaemia. Circulation 53: 1–210

    Google Scholar 

  73. Bing OHL, Brooks WW, Messer JV (1973) Heart muscle viability following hypoxia: protective effect of acidosis. Science 180: 1297–1298

    Article  PubMed  CAS  Google Scholar 

  74. Mjos OD, Miller NE, Riemersma RA, et al. (1976) Effects of dichloroacetate on myocardial substrate extraction, epicardial ST-segment elevation, and ventricular blood flow following coronary occlusion in dogs. Cardiovasc Res 10: 427–436

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council, Heart Research Unit, University of Cape Town, Medical School, Cape Town, 7925, South Africa

    Lionel H. Opie

Authors
  1. Lionel H. Opie
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Physiology, University of Düsseldorf, Düsseldorf, Germany

    Hans Michael Piper

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Kluwer Academic Publishers

About this chapter

Cite this chapter

Opie, L.H. (1990). Importance of glycolytically produced ATP for the integrity of the threatened myocardial cell. In: Piper, H.M. (eds) Pathophysiology of Severe Ischemic Myocardial Injury. Developments in Cardiovascular Medicine, vol 104. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0475-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-0475-0_4

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-0459-3

  • Online ISBN: 978-94-009-0475-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation