Advertisement

Basic Research in Cardiology

, Volume 89, Issue 6, pp 535–544 | Cite as

Is oxygen supply sufficient to induce normoxic conditions in isolated rat heart?

  • C. Poizat
  • C. Keriel
  • P. Cuchet
Original Contributions

Summary

The aim of this study is to assess whether oxygen supply is sufficient to induce normoxic conditions in isolated rat hearts. Hearts are perfused with a Krebs medium supplemented with 11mM glucose, 0.6 mM lactate, 0.06 mM pyruvate, non delipidated albumin (0.1 mM fatty acids), and either 1.78 mM or 0.76 mM free calcium, at 10ml.min−1. Graded hypoxia is induced by a stepwise decrease of partial pressure of oxygen (PO2) from 660 to 52 mmHg. Contractile performance, oxygen uptake and lactate plus pyruvate balance are assessed. With high calcium, left ventricular developed pressure, dP/dt max and oxygen uptake increase linearly with PO2 up to 660 mmHg; heart rate increases with PO2 up to 250 mmHg and then tends to stabilize. With low calcium, all parameters reach a plateau over 400 mmHg. Lactate plus pyruvate production suggests a stimulation of glycolysis with high calcium, even at 660 mmHg; conversely, there is no lactate plus pyruvate production with low calcium over 250 mmHg. In conclusion, our results demonstrate that, under a high level of calcium at a constant flow of 10 ml.min−1, cardiac function is always limited by O2 supply, except for heart rate. This raises the question as to the definition of a normoxic state. The better preservation of heart rate during hypoxia, compared to other dynamic parameters, could be explained by a contribution of glycolytic ATP.

Key words

isolated rat heart graded hypoxia heart function oxygen uptake glycolytic ATP 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bergmeyer HU (1974) Methods of enzymatic analysis. 2nd ed, Verlag Chemie, Academic Press Inc, London, pp 1446–1451, 1464–1468Google Scholar
  2. 2.
    Braunwald E, Rutherford JD (1986) Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium” J Am Coll Cardiol 8:1467–1470Google Scholar
  3. 3.
    Cobbe SM, Poole-Wilson PA (1980) Tissue acidosis in myocardial hypoxia. J Mol Cell Cardiol 12:761–770Google Scholar
  4. 4.
    Deutsch N, Klitzner TS, Lamp ST, Weiss JN (1991) Activation of cardiac ATP-sensitive K+current during hypoxia: correlation with tissue ATP levels. Am J Physiol 261:H671-H676Google Scholar
  5. 5.
    Duvelleroy MA, Duruble M, Martin JL, Teisseire B, Droulez J, Cain M (1976) Blood-perfused working isolated rat heart. J Appl Physiol 41(4):603–607Google Scholar
  6. 6.
    Freisleben HJ, Kriege H, Clarke C, Beyersdorf F, Zimmer G (1991) Hemodynamic and mitochondrial parameters during hypoxia and reoxygenation in working rat hearts. Arzneim-Forsch/Drug Res 41(1) Nr:1 81–88Google Scholar
  7. 7.
    Garland PB, Randle PJ (1964) Control of pyruvate dehydrogenase in the perfused rat heart by the intracellular concentration of acetyl coenzyme A. Biochem J 91:6C-7CGoogle Scholar
  8. 8.
    Griese M, Perlitz V, Jüngling E, Kammermeier H (1988) Myocardial performance and free energy of ATP-hydrolysis in isolated rat hearts during graded hypoxia, reoxygenation and high Ke+-perfusion. J Mol Cell Cardiol 20:1189–1201Google Scholar
  9. 9.
    Guarnieri C, Ferrari R, Visioli O, Caldarera CM, Nayler WG (1978) Effect of α tocopherol on hypoxic-perfused and reoxygenated rabbit heart muscle. J Mol Cell Cardiol 10:893–906Google Scholar
  10. 10.
    Hearse DJ (1979) Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate. Am J Cardiol 44:1115–1121Google Scholar
  11. 11.
    Jacobus WE, Pores IH, Lucas SK, Weisfeldt ML, Flaherty JT (1982) Intracellular acidosis and contractility in the normal and ischemic heart as examined by31P NMR. J Mol Cell Cardiol 14:13–20Google Scholar
  12. 12.
    Kammermeier H, Roeb E, Jüngling E, Meyer B (1990) Regulation of systolic force and contro energy of ATP-hydrolysis in hypoxic hearts. J Mol Cell Cardiol 22:707–713Google Scholar
  13. 13.
    Keung EC, Li Q (1991) Lactate activates ATP-sensitive potassium channels in guinea pig ventricular myocytes. J Clin Invest 88:1772–1777Google Scholar
  14. 14.
    Kübler W, Katz AM (1977) Mechanism of early “pump” failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation. Am J Cardiol 40:467–471Google Scholar
  15. 15.
    Lazzarino G, Nuutinen ME, Tavazzi B, Cerroni L, Di Pierro D, Giardina B (1991) Preserving effect of fructose-1,6-biphosphate on high-energy phosphate compounds during anoxia and reperfusion in isolated Langendorff-perfused rat heart. J Mol Cell Cardiol 23:13–23Google Scholar
  16. 16.
    Liedtke AJ (1981) Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 23:321–336Google Scholar
  17. 17.
    Mazer CD, Stanley WC, Hickey RF, Neese RA, Cason BA, Demas KA, Wineski JA, Gertz EW (1990) Myocardial metabolism during hypoxia: maintained lactate oxidation during increased glycolysis. Metabolism 39(9):913–918Google Scholar
  18. 18.
    Mc Donald TF, Mac Leod DP (1971) Anoxia-recovery cycle in ventricular muscle: action potential duration, contractility and ATP content. Pflügers Arch 325:305–322Google Scholar
  19. 19.
    Mc Donald TF, Mac Leod DP (1973) Metabolism and the electrical activity of anoxic muscle. J Physiol 229:559–582Google Scholar
  20. 20.
    Morena H, Janse MJ, Fiolet JWT, Krieger WJG, Crijns H, Durrer D (1980) Comparison of the effects of regional ischemia, hypoxia, hyperkaliema and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart. Circ Res 46:634–646Google Scholar
  21. 21.
    Nakaya H, Takeda Y, Tohse N, Kanno M (1991) Effects of ATP-sensitive K+channels blockers on the action potential shortening in hypoxic and ischemic myocardium. Br J Pharmacol 103:1019–1026Google Scholar
  22. 22.
    Nayler WG, Poole-Wilson PA, Williams A (1979) Hypoxia and calcium. J Mol Cell Cardiol 11:683–706Google Scholar
  23. 23.
    Newsholme EA, Leech AR (1983) Biochemistry for the medical sciences. John Wiley and Sons, Chichester New York Brisbane Toronto Singapore, p 126Google Scholar
  24. 24.
    Noma A (1983) ATP-regulated K+channels in cardiac muscle. Nature 305:147–148Google Scholar
  25. 25.
    Oliver MF (1976) The influence of myocardial metabolism on ischemic damage. Circulation 53 (3) suppl.I:I 168–170Google Scholar
  26. 26.
    Opie LH, Bricknell OL (1979) Role of glycolytic flux and the effect of glucose in decreasing fatty acid-induced release of lactate dehydrogenase from isolated coronary ligated rat heart. Cardiovasc Res 13:693–702Google Scholar
  27. 27.
    Paradise NF, Schitter JL, Surmits JM (1981) Criteria for adequate oxygenation of isometric kitten papillary muscle. Am J Physiol 241:H348-H353Google Scholar
  28. 28.
    Poizat C, Keriel C, Garnier A, Dubois F, Cand F, Cuchet P (1993) An experimental model of hypoxia on isolated rat heart in a recirculating system: study of fatty acid metabolism with an iodinated fatty acid. Arch Int Biophys Biochim 101:347–356Google Scholar
  29. 29.
    Rahimtoola SH (1989) The hibernating myocardium. Am Heart J 117:211–221Google Scholar
  30. 30.
    Reimer KA, Jennings RB (1986) Myocardial ischemia, hypoxia, and infarction. In: Fozzard HA, Haber E, Jennings RB, Katz A, Morgan HE (eds) The heart and cardiovascular system; Raven Press, New York, pp 1133–1201Google Scholar
  31. 31.
    Saks VA, Lipnia NV, Smirnov VN, Chasov EI (1976) Studies of energy transport in heart cells. The functional coupling between mitochondrial creatine phosphokinase and ATP-ADP translocase: kinetic evidence. Arch Biochem Biophys 173:34–41Google Scholar
  32. 32.
    Silber R, Sauer B, Eigel P, Henrich HA, Elert O (1991) Electron microscopic changes and edema after nine hours' perfusion of isolated canine hearts. Heart Vessels 6(4):203–210Google Scholar
  33. 33.
    Spitzer JJ (1974) Effect of lactate infusion on canine myocardial free fatty acid metabolism in vivo. Am J Physiol 226(1):213–217Google Scholar
  34. 34.
    St John Sutton MG, Ritman EL, Paradise NF (1980) Biphasic changes in maximum relaxation rate during progressive hypoxia in isometric kitten papillary muscle and isovolumic rabbit ventricle. Circ Res 47:516–524Google Scholar
  35. 35.
    Van Beek JHGM, Bouma P, Westerhof N (1989) Oxygen uptake in saline-perfused rabbit heart is decreased to a similar extent during reductions in flow and arterial oxygen concentration. Pflügers Arch 414:82–88Google Scholar
  36. 36.
    Vleugels A, Vereecke J, Carmeliet EE (1980) Ionic curents during hypoxia in voltage clamped cat ventricular muscle. Circ Res 47:501–508Google Scholar
  37. 37.
    Williamson DH, Lund P, Krebs HA (1967) The redox state of free nicotinamide adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J 103:514–527Google Scholar
  38. 38.
    Williamson JR, Ford C, Illingworth J, Safer B (1976) Coordination of citric acid cycle activity with electron transport flux. Circ Res (supp I)38(5):I39-I51Google Scholar

Copyright information

© Steinkopff-Verlag 1994

Authors and Affiliations

  • C. Poizat
    • 1
  • C. Keriel
    • 1
  • P. Cuchet
    • 1
  1. 1.Centre de Physiologie et Physiopathologie CellulairesUniversité Joseph FourierGrenoble, CedexFrance

Personalised recommendations