Oxygen Consumption and Mitochondrial Membrane Potential in Postischemic Myocardium

  • Kazuaki Nishio
  • Noburu Konno
  • Yoshihisa Arata
  • Ryuji Ueda
  • Katumiti Iijima
  • Toshiki Iwata
  • Takashi Katagiri
Part of the Progress in Experimental Cardiology book series (PREC, volume 1)


Oxygen consumption may be disproportionately high relative to contractile function in postischemic reperfused myocardium. The study reported in this chapter investigated the mechanism of the dissociation between oxygen consumption and contractile function in postischemic reperfused myocardium using isolated rat hearts. Mitochondrial dysfunction secondary to increased calcium uptake has been implicated as an important mediator of reperfusion injury in the heart. In postischemic, isovolumic, antegrate-perfused rat hearts, the myocardial oxygen consumption rate (MVO2) and contractile function were studied in relation to mitochondrial function. Left ventricular pressure, coronary blood flow, and oxygen consumption were determined. Mitochondrial respiration and the mitochondrial membrane potential were measured by polarography and flow cytometry, respectively. To examine the role of mitochondrial calcium uptake in ischemia reperfusion injury, isolated rat hearts perfused with ruthenium red, which inhibits calcium uptake by mitochondria, were compared to control perfused hearts. After stabilization, hearts were subjected to 60 minutes of no-flow ischemia, followed by 60 minutes of reperfusion. At 15 minutes after the onset of reperfusion, there was poor recovery of left ventricular developed pressure to 64% of the control level, but myocardial oxygen consumption was increased to 134% of control. The addition of 2.5 μM ruthenium red to the perfusate resulted in a decrease of myocardial oxygen consumption. The oxygen consumption rate in state 3 of mitochondria decreased similarly following reperfusion in control and ruthenium red hearts. The mitochondrial membrane potential was reduced to 89% (logarithmic scale) after 15 minutes of reperfusion and then returned to preischemic level. These data suggest that the dissociation between oxygen consumption and contractile function following early reperfusion is partly caused by the repair of intracellular damage resulting from calcium accumulation to mitochondria.


Oxygen Consumption Mitochondrial Membrane Potential Coronary Flow Contractile Function Oxygen Consumption Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsby WN, Macruz R. 1958. Hemodynamic determinants of oxygen consumption of the heart with special reference to tension-time index. Am J Physiol 192:148–156.PubMedGoogle Scholar
  2. 2.
    Neely JR, Liebermeister H, Battyersby EJ, Morgan HE. 1967. Effect of pressure development on oxygen consumption by isolated rat hearts. Am J Physiol 212:804–814.PubMedGoogle Scholar
  3. 3.
    Stahl LD, Weiss HR, Becker LC. 1988. Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 77:865–872.PubMedGoogle Scholar
  4. 4.
    Laxson DD, Homans DC, Dai X-Z, Sublett E, Bache RJ. 1989. Oxygen consumption and coronory reactivity in postischemic myocardium. Circ Res 64:9–20.PubMedGoogle Scholar
  5. 5.
    Schott RJ, Rohmann S, Braun ER, Schaper W. 1990. Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142.PubMedGoogle Scholar
  6. 6.
    Peng CF, Kane JJ, Straub KD, Murphy ML. 1980. Improvement of mitochondrial energy production in ischemic myocardium by in vivo infusion of ruthenium red. J Cardiovasc Phamacol 2:45–54.CrossRefGoogle Scholar
  7. 7.
    Bourdillon PD, Poole-Wilson PA. 1981. Effects of ischemia and reperfusion on calcium exchange and mechanical function in isolated rabbit myocardium. Cardiovasc Res 15:121–130.PubMedGoogle Scholar
  8. 8.
    Bussen P. 1985. Suppression of cellular injury during the calcium paradox in rat heart by factors which reduce calcium uptake by mitochondria. Pflugers Arch 404:166–171.CrossRefGoogle Scholar
  9. 9.
    Huang XQ, Liedtke AJ. 1989. Alterations in fatty acid oxidation in ischemic and reperfused myocardium. Mol Cell Biochem 88:145–153.PubMedCrossRefGoogle Scholar
  10. 10.
    Kusuoka H, Koretune Y, Chacko VP, Weisfeldt ML, Marban E. 1990. Excitation-contraction coupling in postischemic myocardium: does failure of activator Ca2+ transients underlie stunning? Circ Res 66:1268–1276.PubMedGoogle Scholar
  11. 11.
    Trach V, Buschmans-Denkel E, Schaper W. 1986. Relation between lipolysis and glycolysis during ischemia in the isolated rat heart. Basic Res Cardiol 81:454–464.PubMedCrossRefGoogle Scholar
  12. 12.
    Sordahl LA, Stewart ML. 1980. Mechanism(s) of altered mitochondrial calcium transport in acutely ischemic canine hearts. Circ Res 47:814–820.PubMedGoogle Scholar
  13. 13.
    Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin phenol regent. J Biol Chem 193:265–275.PubMedGoogle Scholar
  14. 14.
    Ronald KE, Emaus RG, John JL. 1986. Rhodamine 123 as the transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim Biophys Acta 850:436–448.CrossRefGoogle Scholar
  15. 15.
    Dean EN, Nicklas JM. 1990. The oxygen consumption paradox of “stunned myocardium” in dogs. Basic Res Cardiol 85:120–131.PubMedCrossRefGoogle Scholar
  16. 16.
    Benzi RH, Lerch R. 1992. Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administered during reperfusion. Circ Res 71:567–576.PubMedGoogle Scholar
  17. 17.
    Swain JL, Sabina RL, McHale PA, Greenfield JC Jr, Holmes EW. 1982. Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. Am J Physiol 242 (Heart Circ Physiol 11):H88–H826.Google Scholar
  18. 18.
    Zimmer SD, Michurski SP, From AHL, Foker JE, Ugrbil K. 1987. 31P NMR studies of myocardial bioenergics in the post-ischemic myocardium. Proc Soc Magnetic Resonance Med 2:554.Google Scholar
  19. 19.
    Hoffmeister HM, Mauser M, Schaper W. 1986. Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels. Basic Res Cardiol 81:358–372.CrossRefGoogle Scholar
  20. 20.
    Marbon E, Kitakaze M, Koretsune Y, Yue DT, Chacko VP, Pike MM. 1990. Quantification of [Ca2+]i in perfused hearts. Critical evaluation of the 5F-BAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. Circ Res 66:1255–1267.Google Scholar
  21. 21.
    Gunter TE, Peeifer DR. 1990. Mechanism by which mitochondria transport calcium. Am J Physiol 258:C755–C786.PubMedGoogle Scholar
  22. 22.
    Versi A, Reynafarje B, Lehninger A. 1978. Stoichiometry of H+ ejection and Ca2+ uptake couple to electron transport in rat heart mitochondria. J Biol Chem 253:6379–6385.Google Scholar
  23. 23.
    Ferrari R, di Lisa, Raddino R, Visioli O. 1982. The effects of ruthenium red on mitochondrial function during post-ischemic reperfusion. J Mol Cell Cardiol 14:737–740.PubMedCrossRefGoogle Scholar
  24. 24.
    Richter C, Frei B. 1988. Ca2+ release from mitochondria induced by prooxidants. Free Rad Biol Med 4:365–375.PubMedCrossRefGoogle Scholar
  25. 25.
    Frei B, Richter C, 1988. Mono (ADP-ribosylation) in rat liver mitochondria. Biochem 27:529–535.CrossRefGoogle Scholar
  26. 26.
    Kusuoka H, Porterfield JK, Weismann HF. 1987. Pathophysiology and pathogenesis of stunned myocardium. Depression-Ca2+ activity of contraction as a consequance of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 79:950–996.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Kazuaki Nishio
    • 1
  • Noburu Konno
    • 1
  • Yoshihisa Arata
    • 1
  • Ryuji Ueda
    • 1
  • Katumiti Iijima
    • 1
  • Toshiki Iwata
    • 1
  • Takashi Katagiri
    • 1
  1. 1.Showa University School of MedicineJapan

Personalised recommendations