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Oxidative Stress in Heart Failure: Current Understanding and Prospective

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Abstract

Our knowledge of the pathophysiology of heart failure has advanced far beyond the classic concept of the hemodynamic overload model and associated neurohumoral changes. Current interest lies in understanding the fundamentals of cellular defects to identify new molecular targets for therapies. Some of the new target sites being explored are inflammatory cytokines, nitric oxide, oxidative stress and apoptosis during the remodelling processes such as cardiac hypertrophy and dilation. The present review provides an overview of the chemistry/biochemistry of free radicals as well as a discussion of some defense mechanisms that have evolved and adapted to combat these toxic oxygen species. The probable role of oxidative stress in the pathogenesis of heart failure both from animal data and heart failure patients is also presented.

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References

  1. Singal PK, Khaper N, Palace V, Kumar D. The role of oxidative stress in the genesis of heart disease. Cardiovasc Res 1998;40:426–432.

    Google Scholar 

  2. Lavoisier A-L. Alterations qu'eprouve 1'air resire. Recueil des memoires de Lavoisier. 1785, Read to the Societe de Medicine. Reprinted as part of “Memoires sur la Respiration et al Transpiration des Animaux” in “Les Maitres de la Pensee Scientifique.” Paris: Gauthier-Villaus et cie (eds.), 1920.

  3. Smith JL. Pathological effects due to increase of oxygen tension in air breathed. J Physiol 1899;24:19–35.

    Google Scholar 

  4. Gomberg M. An instance of trivalent carbon: Triphenylmethyl. J Am Chem Soc 1900;22:757–761.

    Google Scholar 

  5. Gerschman R, Gilbert DL, Nye SW, Swyer P, Fenn WO. Oxygen poisoning and X-irradiation: A mechanism in common. Science 1954;119:623–626.

    Google Scholar 

  6. McCord JM, Fridovich I. Superoxide dismutase. An enzymatic function for erythrocuprein (hemecuprein). J Biol Chem 1969;244:6049–6055.

    Google Scholar 

  7. Halliwell B. Oxidants and human disease: Some new concepts. FASEB J 1987;1:358–364.

    Google Scholar 

  8. Weiss SJ. Oxygen, ischemia and inflammation. Acta Physiol Scand 1986;548:9–31.

    Google Scholar 

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

    Google Scholar 

  10. Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: A concise review. J Mol Cell Cardiol 1987;19:817–828.

    Google Scholar 

  11. Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol 1988;12:239–249.

    Google Scholar 

  12. Singal PK, Hill MF, Ganguly NK, Khaper N, Kirshenbaum LA, Pichardo J. Role of oxidative stress in heart failure subsequent to myocardial infarction. L'information Cardiologique. 1996;20:343–362.

    Google Scholar 

  13. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. Free radicals and the heart. J Pharmacol Toxicol Meth 1993;30:55–67.

    Google Scholar 

  14. Singal PK, Petkau A, Gerrard JM, Hrushovetz S, Foerster J. Free radicals in health and disease. Mol Cell Biochem 1988;84:121–122.

    Google Scholar 

  15. Singh N, Dhalla AK, Seneviratne CK, Singal PK. Oxidative stress and heart failure. Mol Cell Biochem 1995;147:77–81.

    Google Scholar 

  16. Saran M, Michel C, Bors W. Reactions of NO with O2¯?. Implications for the action of endothelium-derived relaxing factor. Free Radical Res Commun 1989;10:221–226.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  19. Kaneko M, Singal PK, Dhalla NS. Alterations in heart sarcolemmal Ca21 binding activities due to oxygen radicals. Basic Res Cardiol 1990;85:45–54.

    Google Scholar 

  20. Reeves JP, Bailey CA, Hale CC. Redox modification of so–Oxidative Stress and Heart Failure 117 dium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 1986;201:4948–4955.

    Google Scholar 

  21. 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 1984;55:120–124.

    Google Scholar 

  22. Dixon IM, Kaneko M, Hata T, Panagia V, Dhalla NS. Alterations in cardiac membrane Ca11 transport during oxidative stress. Mol Cell Biochem 1990;99:125–133.

    Google Scholar 

  23. Ferrari R, Ceconi C, Curello S, Guarnieri C, Calderera CM, Albertini A, Visioli O. Oxygen-mediated myocardial damage during ischemia and reperfusion: Role of the cellular defenses against oxygen toxicity. J Mol Cell Cardiol 1985;17:93–945.

    Google Scholar 

  24. Fridovich I. The biology of oxygen radicals. Science 1978;20 1:875–880.

    Google Scholar 

  25. Ferrari R, Agnoletti L, Comini L, Gata G, Bachetti T, Cargnoni A, Ceconi C, Curello S, Visioli O. Oxidative stress during myocardial ischemia and heart failure. Eur Heart J 1998;19:B2–B11.

    Google Scholar 

  26. Lawrence RA, Burk RE. Species, tissue and subcellular distribution of non-selenium dependent glutathione peroxidase activity. J Nutr 1978;108:211–215.

    Google Scholar 

  27. Freeman BA, Crapo JD. Biology of disease. Free radicals and tissue injury. Lab Invest 1982;47:412–425.

    Google Scholar 

  28. Packer L. Vitamin E is nature's master antioxidant. Scientific American Science and Medicine 1994;54–63.

  29. Packer L. Protective role of vitamin E in biological systems. Am J Clin Nutr 1991;53:1050–1055.

    Google Scholar 

  30. Singal PK, Ghani RA-A; Khaper N, Palace V, Hill MF. Antioxidant adaptations and cardiac dysfunction: Involvement of vitamin E. J Adapt Med 1997;1:5–15.

    Google Scholar 

  31. Ozer NK, Boscoboinik A, Azzi A. New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis. Biochem Mol Bio Int 1995;35:117–124.

    Google Scholar 

  32. Packer JE, Slater TF, Watson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 1979;278:737–738.

    Google Scholar 

  33. Foote CS, Denny RW. Chemistry of singlet oxygen VII. Quenching by b-carotene. J Am Chem Soc 1968;90:6233–6235.

    Google Scholar 

  34. Riemersma RA. Epidemiology and the role of antioxidants in preventing coronary heart disease:A brief overview. Proc Nutr Soc 1994;53:59–65.

    Google Scholar 

  35. Palace VP, Khaper N, Qin Q, Singal PK. Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Rad Biol Med 1999 26:746–761.

    Google Scholar 

  36. Clark IA, Cowden WB, Hunt NH. Free radical-induced pathology. Medicinal Research Review 1985;5:297–332.

    Google Scholar 

  37. Reed DJ. Glutathione: Toxicological implications. Ann Rev Pharmacol Toxicol 1990;30:603–631.

    Google Scholar 

  38. Reed DJ. Glutathione depletion and susceptibility. Pharmacol Rev 1984;36:35S–33S.

    Google Scholar 

  39. Verma A, Hill M, Bhayana S, Pichardo J, Singal PK. Role of glutathione in acute myocardial adaptation. In: Adaptation Biology and Medicine: Subcellular Basis, Sharma BK, Takeda N, Ganguly NK, Singal PK, eds. New Delhi, India: Narosa Publishers, Vol. 1, 1997;399–408.

    Google Scholar 

  40. Ames BN, Cathcart R, Schivears E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant and radical caused aging and cancer. Proc Natl Acad Sci USA 1981;78:6858–6862.

    Google Scholar 

  41. Bernier M, Hearse DJ, Manning AS. Reperfusion-induced arrhythmias and oxygen-derived free radicals: Studies with “anti-free radical” interventions and a free radical-generating system in the isolated perfused rat heart. Circ Res 1986;58:331–340.

    Google Scholar 

  42. Chopra K, Singh M, Kaul N, Andrabi KI, Ganguly NK. Decrease of myocardial infarct size with desferrioxamine: Possible role of oxygen free radicals in its ameliorative effect. Mol Cell Biochem 1992;113:71–76.

    Google Scholar 

  43. Forsmark P, Aberg F, Norling B, Nordenbrand K, Dallner G, Ernster L. Inhibition of lipid peroxidation by ubiquinol in submitochondrial particles in the absence of vitamin E. FEBS Lett 1991;285:39–43.

    Google Scholar 

  44. Halliwell B, Gutteridge JMC. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1984;1396–1397.

  45. Kappus H. Lipid peroxidation: Mechanisms, analysis, enzymology and biological relevance. In: Oxidative Stress, Sies H, ed. London: Academic Press, 1985:273–303.

    Google Scholar 

  46. Ceconi C, Cargnoni A, Pasini E, Condorelli E, Curello S, Ferrari R. Evaluation of phospholipid peroxidation as malondialdehyde during myocardial ischemia and reperfusion injury. Am J Physiol 1991;260:H1057–H1061.

    Google Scholar 

  47. Sies H, ed. Oxidative Stress, Oxidants and Antioxidants. London and New York: Academic Press, 1991.

    Google Scholar 

  48. Arroyo CM, Kramer JH, Dickens BF, Weglicki WB. Identification of free radicals in myocardial ischemia/reperfusion by spin trapping with nitron DMPO. FEBS Lett 1987;221:101–104.

    Google Scholar 

  49. Garlick PB, Davies MJ, Hearse DJ, Slater TF. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res 1987;61:757–760.

    Google Scholar 

  50. Currello S, Ceconi C, de Giuli F, Panzali AF, Milanesi B, Calarco M, Pardini A, Marzollo P, Alfieri O, Messineo F, Ferrari R. Oxidative stress during reperfusion of human hearts: Potential sources of oxygen free radicals. Cardiovasc Res 1995;29:118–125.

    Google Scholar 

  51. Levy Y, Bartha P, Ben-Amotz A, Brook JG, Danker G, Lin S, Hammerman H. Plasma antioxidants and lipid peroxidation in acute myocardial infarction and thrombolysis. J Am Coll Nutr 1998;17:373–341.

    Google Scholar 

  52. Jeroudi MO, Hartely CJ, Bolli R. Myocardial reperfusion injury: Role of oxygen free radicals and potential therapy with antioxidants. Am J Cardiol 1994;73:2B–7B.

    Google Scholar 

  53. Ferrari R, Alfieri O, Currello S, Ceconi C, Cargnoni A, Marzollo P, Pardini A, Caradonna E, Visioli O. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 1990;81:201–211.

    Google Scholar 

  54. Palace V, Kumar D, Hill MF, Khaper N, Singal PK. Regional differences in non-enzymatic antioxidants in the heart under control and oxidative stress conditions. J Mol Cell Cardiol 1999 31:193–202.

    Google Scholar 

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

    Google Scholar 

  56. Chen EP, Bittner HB, Davis RD, Van Trigt P, Folz RJ. Physiologic effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. J Thorac Cardiovasc Surg 1998;115:450–458.

    Google Scholar 

  57. Klein HH, Lindert PS, Buchwald A, Nerbendalh K, Kreuzer H. Intracoronary superoxide dismutase for the treatment of reperfusion injury. A blind randomized placebo-controlled trial in ischemic-reperfused porcine hearts. Basic Res Cardiol 1988;83:141–148.

    Google Scholar 

  58. Shattock MJ. Do we know the mechanism of myocardial stunning? Basic Res Cardiol 1998;93:145–149.

    Google Scholar 

  59. Bolli R. Causative role of oxyradicals in myocardial stunning: A proven hypothesis. Basic Res Cardiol 1998;93:156–172.

    Google Scholar 

  60. Li Q, Bolli R, Qiu Y, Tang XL, Murphee SS, French BA. Gene therapy with extracellular superoxide dismutase attenuates myocardial stunning in conscious rabbits. Circulation 1998;98:1438–1448.

    Google Scholar 

  61. Francis GS, Goldsmith SR, Cohn JN. Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J 1982;104:725–731.

    Google Scholar 

  62. Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol-induced oxidative stress in rat tissues. Pharmacol Res 1998;38:297–303.

    Google Scholar 

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

    Google Scholar 

  64. Singal PK, Tong J. Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes. Mol Cell Biochem 1988;84:163–171.

    Google Scholar 

  65. Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res 1983;43:460–472.

    Google Scholar 

  66. Siveski-Iliskovic N, Kaul N, Singal PK. Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats. Circulation 1994;89:2829–2835.

    Google Scholar 

  67. Singal PK, Iliskovic N, Li T, Kumar D. Adriamycin cardiomyopathy: Pathophysiology and prevention. FASEB J 1997;11:931–936.

    Google Scholar 

  68. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Eng J Med 1998;339:900–905.

    Google Scholar 

  69. Myers CE, McGuire WP, Liss RH, Infirm I, Grutzinger K, Young RC. Adriamycin: The role of lipid peroxidation in cardiac toxicity and tumour response. Science 1977;19: 165–167.

    Google Scholar 

  70. Kaul N, Siveski-Iliskovic N, Thomas TP, Hill M, Singh N, Singal PK. Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy. Nutrition 1995;11:551–554.

    Google Scholar 

  71. Paolisso G, D'Amore A, Giugliano D, Ceriello A, Varricchio M, D'Onofrio F. Pharmacological doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr 1993;57:650–656.

    Google Scholar 

  72. Giugliano D, Ceriello A, Paolisso G. Diabetes mellitus, hypertension, and cardiovascular disease: Which role for oxidative stress? Metabolism 1995;44:363–368.

    Google Scholar 

  73. Wohaieb SA, Godin DV.Alterations in free radicals tissue-defense mechanisms in streptozotocin-induced diabetes in rat. Effects of insulin treatment. Diabetes 1987;36:1014–1018.

    Google Scholar 

  74. Gupta M, Singal PK. Higher antioxidative capacity during a chronic stable heart hypertrophy. Circ Res 1989;64:398–406.

    Google Scholar 

  75. Kirshenbaum LA, Singal PK. Increase in endogenous antioxidant enzymes protects hearts against reperfusion injury. Am J Physiol 1993;2265:H484–H497.

    Google Scholar 

  76. Dhalla AK, Singal PK. Antioxidant changes in hypertrophied and failing guinea pig hearts. Am J Physiol 1994; 266(Heart & Circ Physiol 36):H1280–H1285.

    Google Scholar 

  77. Dhalla AK, Hill MF, Singal PK. Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 1996;28:506–514.

    Google Scholar 

  78. Kirshenbaum LA, Hill M, Singal PK. Endogenous antioxidants in isolated hypertrophied cardiac myocytes and hypoxia–reoxygenation injury. J Mol Cell Cardiol 1995;27: 263–272.

    Google Scholar 

  79. Prasad K, Gupta JB, Kalra J, Lee P, Mantha SV, Bharadwaj B. Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model. JMol Cell Cardiol 1996;28:375–385.

    Google Scholar 

  80. Hill MF, Singal PK. Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am J Pathol 1996;148:291–300.

    Google Scholar 

  81. Palace VP, Hill MF, Farahmand F, Singal PK. Mobilization of antioxidant vitamin pools and hemodynamic function following myocardial infarction. Circulation 1999a;9:121–126.

    Google Scholar 

  82. Hill MF, Singal PK. Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation 1997;96:2414–2420.

    Google Scholar 

  83. Khaper N, Singal PK. Effects of afterload reducing drugs on the pathogenesis of antioxidant changes and congestive heart failure in rats. J Am Coll Cardiol 1997;29:856–861.

    Google Scholar 

  84. Khaper N, Hill MF, Pichardo J, Singal PK. Effects of captopril on myocardial oxidative stress changes in post-MI rats. In: Angiotensin II Blockade, Dhalla NS, Zahradka, P, Dixon IMC, Beamish RE. Boston: Kluwer Academic Publishers, 1998; 527–536.

    Google Scholar 

  85. Axford-Gately RA, Wilson GJ. Reduction of experimental myocardial infarct size by oral administration of alpha tocopherol. Cardiovasc Res 1991;25:89–92.

    Google Scholar 

  86. Mickle DA, Li RK, Weisel RD. Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction. Ann Thorac Surgery 1989;47:553–557.

    Google Scholar 

  87. Massey KD, Burton KP. Alpha-tocopherol attenuates myocardial membrane-related alterations resulting from ischemia–reperfusion. Am J Physiol 1989;256:H1192–1199.

    Google Scholar 

  88. Klein HH, Pich S, Lindert S, Nibendahl K, Niedman P, Kreuzer H. Combined treatment with vitamins E and C in experimental myocardial infarction in pigs. Am Heart J 1989;118:667–673.

    Google Scholar 

  89. Klein HH, Pich S, Lindert S, Nebendahl K, Niedman P. Failure of chronic high dose oral vitamin E treatment to protect the ischemic-reperfused porcine heart. J Mol Cell Cardiol 1993;25:103–112.

    Google Scholar 

  90. Belch JJ, Bridges AB, Scott N, Chopra M. Oxygen free radicals and congestive heart failure. Br Heart J 1991;65:245–248.

    Google Scholar 

  91. McMurray J, Mclay J, Chopra M, Bridges A, Belch JJF. Evidence for enhanced free radical activity in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 1990;65:1261–1262.

    Google Scholar 

  92. Diaz-Velez CR. Garcia-Castineiras S, Mendoza-Ramos E, Hernandez-Lopez E, Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am Heart J 1996;131:146–152.

    Google Scholar 

  93. Sobotka PA, Brottman MD, Weitz Z, Birnbaum AJ, Skosey JL, Zarling EJ. Elevated breath pentane in heart failure reduced by free radical scavenger. Free Rad Biol Med 1993;14:643–647.

    Google Scholar 

  94. Weitz ZW, Birnbaum AJ, Sobotka S, Zarling EJ, Skosey JL. High breath concentration during acute myocardial infarction. Lancet 1991;337:933–935.

    Google Scholar 

  95. Charney RH, Levy DK, Kalman J, Buchholz E, et al. Free radical activity increased with NYHA class in congestive heart failure. J Am Coll Cardiol 1997;29:930–939.

    Google Scholar 

  96. Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN. Increased oxidative stress in Oxidative Stress and Heart Failure patients with congestive heart failure. J Am Coll Cardiol 1998;31:1352–1356.

    Google Scholar 

  97. Yucel D, Aydogdu S, Cehreli S, Saydam G, Canatan H, Senes M, Cigdem Topkaya B, Nebioglu S. Increased oxidative stress in dilated cardiomyopathic heart failure. Clin Chem 1998;44:148–154.

    Google Scholar 

  98. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willet WC. Vitamin E consumption and the risk of coronary disease in men. N Engl J Med 1993;328:1450–1456.

    Google Scholar 

  99. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328: 1444–1449.

    Google Scholar 

  100. Singh RB, Niaz MA, Rastogi S. Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian experiment of infarct survival-3). Am J Cardiol 1996;77:232–236.

    Google Scholar 

  101. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–786.

    Google Scholar 

  102. Kok FJ, de Bruijn AM, Vermeeren R, Hofman A, van Laar A, de Bruin M, Hermus RJ, Valkenburg HA. Serum selenium, vitamin antioxidants and cardiovascular mortality: A nine year follow-up study in the Netherlands. Am J Clin Nutr 1987;45:462–468.

    Google Scholar 

  103. Hense HW, Stender M, Bors W, Keil V. Lack of an association between serum vitamin E and myocardial infarction in a population with high vitamin E levels. Atherosclerosis 1993;103:21–28.

    Google Scholar 

  104. Gottlieb RA. Burleson KO, Kloner RA, Babior BM, Engler RL. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 1994;94:1621–1628.

    Google Scholar 

  105. Kajstura J, Liu Y, Baldini A, Li B, Olivetti G, Leri A, Anversa P. Coronary artery constriction in rats: necrotic and apoptotic myocyte death. Am J Cardiol 1998;82:30K–41K.

    Google Scholar 

  106. Teiger E, Than VD, Richard L, Wisnewsky C, Tea BS, Gaboury L, Tremblay J, Schwartz K, Hamet P. Apoptosis in pressure-overload induced heart hypertrophy in the rat. J Clin Invest 1996;97:2891–2897.

    Google Scholar 

  107. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunology Today 1994;15:7–10.

    Google Scholar 

  108. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipo-Pulkki L-M. Apoptosis in human acute myocardial infarction. Circulation 1997;95:320–323.

    Google Scholar 

  109. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in myocytes in end-stage heart failure. N Engl J Med 1996;335:1182–1189.

    Google Scholar 

  110. Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, DeLoreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P. Apoptosis in the failing human heart.N Engl J Med 1997;336:1131–1141.

    Google Scholar 

  111. Lebovitz RM, Zhang H, Vogel H, Cartwright J Jr, Dionne L, Lu N, Huang S, Matzuk MM. Neurodegeneration, myocardial injury and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci 1996;93: 9782–9787.

    Google Scholar 

  112. Kirshenbaum LA, de Moissac D. The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 1997;96:1580–1585.

    Google Scholar 

  113. Hockenbery DM, Oltavi ZN, Yin XM, Milliman CL, Korsmeyer ST. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993;75:241–251.

    Google Scholar 

  114. Krown KA, Page MT, Nguyen C, Zechner D, Gutierrez V, Comstock KL, Glembotski CC, Quintana PJ, Sabbadini RA. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 1996;98:2854–2865.

    Google Scholar 

  115. Bozkurt B, Kribbs SB, Chubb FJ Jr, Michael LH, Didenko VV, Hornsby PJ, Seta Y, Oral H, Spinale FG, Mann DL. Pathophysiologically relevant concentrations of tumor necrosis factor-a promote progressive left ventricular dysfunction and remodelling in rats. Circulation 1998;97:1382–1391.

    Google Scholar 

  116. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in congestive heart failure. N Eng J Med 1990;323:236–241.

    Google Scholar 

  117. Givertz MM, Colucci WS.New targets for heart failure therapy: endothelin, in_ammatory cytokines, and oxidative stress. Lancet 1998;352(Suppl 1):34–38.

    Google Scholar 

  118. Blum A, Miller H. Role of cytokines in heart failure. Am Heart J 1998;135:181–186.

    Google Scholar 

  119. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, Thompson M, Giroir B. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. Circulation 1998;97:1375–1381.

    Google Scholar 

  120. Nakamura K, Fushimi K, Kouchi H, Mihara K, Miyazaki M, Ohe T, Namba M. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-a and angiotensin II. Circulation 1998;98:794–799.

    Google Scholar 

  121. Meldrum DR, Dinarello CA, Cleveland JC Jr, Cain BS, Shames BD, Meng X, Harken AH. Hydrogen peroxide induces tumor necrosis factor a-mediated cardiac injury by a p38 nitrogen-activated protein kinase-dependent mechanism. Surgery 1998;124:291–296.

    Google Scholar 

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

    Pawan K. Singal, Neelam Khaper, Vince Palace & Dinender Kumar

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Singal, P.K., Khaper, N., Palace, V. et al. Oxidative Stress in Heart Failure: Current Understanding and Prospective. Heart Fail Rev 4, 1–10 (1999). https://doi.org/10.1023/A:1009816106263

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