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Time-course of cardiac myocyte injury due to oxidative stress

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Abstract

Time course of changes in cell morphology, cation content, lipid peroxidation and high energy phosphates was examined in isolated rat cardiac myocytes exposed to oxygen radicals for 0 to 20 min. Xanthine (2 mM) and xanthine oxidase (10 U/L) mixture was used as a source of oxygen radicals. A significant decrease in the number of rod-shape cells with a concomitant increase in the number of hypercontracted cells was observed within 5 min of exposure to xanthine-xanthine oxidase (x-xo). At 10,15 and 20 min of exposure to x-xo, there was a time-dependant increase in the number of round cells. Lipid peroxide content, as indicated by the thiobarbituric acid reactive material, was significantly and progressively increased between 10 to 20 min of perfusion with x-xo. In myocytes exposed to x-xo, Ca2+ and Na+ were increased by 15% and 45% at 15 min and by 55% and 100% at 20 min respectively. Levels of adenosine tri- and di- phosphates were significantly depressed and that of adenosine mono- phosphate were higher at 20 min. These data support the hypothesis that reactive oxygen intermediates can directly influence myocyte structure and function, but these changes seem to occur more slowly in isolated myocytes than in whole hearts.

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References

  1. Chambers DE, Parks DA, Patterson G, Roy R, McCord JM, Yoshida S, Parmley LF, Downey JM: Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol 17: 145–152, 1985

    Google Scholar 

  2. Dhaliwal H, Kirshenbaum LA, Randhawa AK, Singal PK: Correlation between antioxidant changes during hypoxia and recovery upon reoxygenation. Am J Physiol 260: H909-H916, 1991

    Google Scholar 

  3. Guarnieri C, Flamigni F, Caldarera CM: Role of oxygen in the cellular damage induced by reoxygenation of hypoxic heart. J Mol Cell Cardiol 12: 797–808, 1980

    Google Scholar 

  4. Hess ML, Manson NH, Okabe E: Involvement of free radicals in pathophysiology of ischemic heart disease. Can J Physiol Pharmacol 60: 1382–1389, 1982

    Google Scholar 

  5. Jolly SR, Kane WJ, Bailie MD, Abrams GD, Lucchesi BR: Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 54: 277–285, 1984

    Google Scholar 

  6. Myers CE, McGuire WP, Liss RH, Irfirm I, Grotsing K, Young RC: Adriamycin, the role of lipid peroxidation in cardiotoxicity and tumor response. Science (Washington DC), 197: 165–167, 1977

    Google Scholar 

  7. Singal PK, Kapur N, Dhillon KS, Beamish RE, Dhalla NS: Role of free radicals in catecholamine-induced cardiomyopathy. Can J Physiol Pharmacol 60: 1390–1397, 1982

    Google Scholar 

  8. Singal PK, Beamish RE, Dhalla NS: Potential oxidative pathways of catecholamines in the formation of lipid peroxide and genesis of heart disease. Adv Exp Med Biol 161: 391–401, 1983

    Google Scholar 

  9. Singal PK, Deally CMR, Weinberg LE. Subcellular effects of adriamycin in the heart- a concise review. J Mol Cell Cardiol 19: 817–828, 1987

    Google Scholar 

  10. Kirshenbaum LA, Gupta M, Thomas TP, Singal PK: Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy. Can J Cardiol 6: 71–74, 1990

    Google Scholar 

  11. Chance B, Seis H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527–605, 1979

    Google Scholar 

  12. Plaa GL, Witsche H: Chemicals, drugs and lipid peroxidation. Annu Rev Pharmacol 16: 125–141, 1976

    Google Scholar 

  13. Eley DW, Korecky B, Fliss H: Dithiothreitol restores contractile function to oxidant-injured cardiac muscle. Am J Physiol 257: (4 Pt. 2) H1321-H1325, 1989

    Google Scholar 

  14. Gupta M, Gamerio A, Singal PK: Reduced vulnerability of the hypertrophied rat heart to oxygen radical injury. Can J Physiol Pharmacol 65: 1157–1164, 1987

    Google Scholar 

  15. Gupta M, Singal PK: Time course of structure, function and metabolic changes due to an exogenous source of oxygen metabolites in rat heart. Can J Physiol Pharmacol 67: 1549–1559, 1989

    Google Scholar 

  16. Blaustein AS, Schine L, Brooks WW, Fanburg BL, Bing OHL: Influence of exogenously generated oxidant species on myocardial function. Am J Physiol 250: H595-H599, 1986

    Google Scholar 

  17. Rowe GT, Manson NH, Caplan M, Hess ML: Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Circ Res 53: 584–591, 1983

    Google Scholar 

  18. Kaneko M, Singal PK, Dhalla NS: Alterations in heart sarcolemmal Ca2+-ATPase and Ca2+-binding activities due to oxygen free radicals. Basic Res Cardiol 85: 45–54, 1990

    Google Scholar 

  19. Kramer JH, Mak IT, Weglicki WB: Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical induced lipid peroxidation. Circ Res 55: 120–124, 1984

    Google Scholar 

  20. Bihler I, Ho K, Sawh PC: Isolation of calcium-tolerant myocytes from adult rat heart. Can J Physiol Pharmacol 62: 581–588, 1984

    Google Scholar 

  21. Bihler I, Thomas TP, Singal PK: Isolate cardiac myocytes methodology. Appendix I. Can J Cardiol 3: 30–32, 1987

    Google Scholar 

  22. Hohl C, Ansel A, Altschuld R: Contracture of isolated rat heart cells on anaerobic to aerobic transition. Am J Physiol 242: H1022–1030, 1982

    Google Scholar 

  23. Stern MD, Chien AM, Capograssi MC, Pelto DJ, Lakatta E: Direct observation of the ‘oxygen paradox’ in single rat ventricular myocytes. Circ Res 56: 899–903, 1985

    Google Scholar 

  24. Hunter FE, Gebicke JM, Hoffstein PE, Weinstein J, Scott A: Swelling and lysis of rat liver mitochondria induced by ferrous ions. J Biol Chem 238: 828–835, 1963

    Google Scholar 

  25. Singal PK, Pierce GN: Adriamycin stimulates low affinity Ca2+-binding and lipid peroxidation but depresses myocardial function. Am J Physiol 250: H419-H425, 1986

    Google Scholar 

  26. Khatter JC, Singal PK, Bharadwaj B, Prasad K: Cardiac intracellular and blood electrolytes in chronic mitral insufficiency. J Physiol (Paris) 74: 535–540, 1978

    Google Scholar 

  27. Willis JB: Determination of calcium and magnesium in urine by atomic absorption spectroscopy. Analytical Chem 33: 556–559, 1961

    Google Scholar 

  28. Sellevold OF, Jynge P, Aarstad K: High performance liquid chromatography: a rapid isocratic method for determination of creatine compounds and adenine nucleotides in myocardial tissue. J Mol Cell Cardiol 18: 517–527, 1986

    Google Scholar 

  29. Lowery OH, Rosebrough NJ, Farr AL, Randall AJ: Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275, 1951

    Google Scholar 

  30. Montani J, Bagby GJ, Burns AH, Spitzer JJ. Exogenous substrate utilization in Ca2+-tolerant myocytes from adult rat hearts. Am J Physiol 240: H659-H663, 1981

    Google Scholar 

  31. McCay PB, King MM, Lai EK, Poyer JL: The effect of antioxidants on free radical production during in vivo metabolism of carbon tetrachloride. J Am Coll Toxicol 3: 195–206, 1983

    Google Scholar 

  32. Altschuld RA, Hostetler SH, Brierly GP: Response of isolated rat hearts to hypoxia, reoxygenation and acidosis. Circ Res 49: 307–316, 1981

    Google Scholar 

  33. Singal PK, Kirshenbaum LA: A relative deficit in antioxidant reserve may contribute in cardiac failure. Can J Cardiol 6(2): 47–49, 1990

    Google Scholar 

  34. Grinwald PM, Brosnahan C: Sodium imbalance as a cause of calcium overload in post-hypoxic reoxygenation injury. J Mol Cell Cardiol 19: 487–495, 1987

    Google Scholar 

  35. Tani M, Neely JR: Role of intracellular Na+ in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts: possible involvement of H+-Na+ and Na+-Ca2+ exchange. Circ Res 65: 1045–1056, 1989

    Google Scholar 

  36. Lazdunski M, Frelin C, Vigne P: The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulatory internal concentrations of sodium and internal pH. J Mol Cell Cardiol 17: 1029–1042, 1985

    Google Scholar 

  37. McDonough KH, Henry JJ, Spitzer JJ: Effects of oxygen radicals on substrate oxidation by cardiac myocytes. Biochim Biophys Acta 926: 127–131, 1987

    Google Scholar 

  38. Poole-Wilson PA, Harding GP, Bardillion PDV, Tones MA: Calcium out of control. J Mol Cell Cardiol 16: 175–187, 1984

    Google Scholar 

  39. Beauchamp C, Fridovich I: A mechanism for the production of ethylene from methional. J Biol Chem 245: 4641–4646, 1970

    Google Scholar 

  40. Tate RM, Vanbenthuysen KM, Shasby DM, McMurty IF, Repine JE: Oxygen-radical-mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs. Am Rev Respir Dis 126: 802–805, 1982

    Google Scholar 

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Authors and Affiliations

  1. Division of Cardiovascular Sciences, Department of Physiology and St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    L. A. Kirshenbaum, T. P. Thomas, A. K. Randhawa & P. K. Singal

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  1. L. A. Kirshenbaum
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  2. T. P. Thomas
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  3. A. K. Randhawa
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  4. P. K. Singal
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Kirshenbaum, L.A., Thomas, T.P., Randhawa, A.K. et al. Time-course of cardiac myocyte injury due to oxidative stress. Mol Cell Biochem 111, 25–31 (1992). https://doi.org/10.1007/BF00229570

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