Increased oxidative stress in patients with congestive heart failure

Toronto Hospital, Centre for Cardiovascular Research, Ontario, Canada.

OBJECTIVES: We sought to study the markers of lipid peroxidation and defenses against oxidative stress in patients with varying degrees of heart failure. BACKGROUND: Despite advances in other areas of cardiovascular disease, the morbidity and mortality from congestive heart failure (CHF) are increasing. Data mainly from animal models suggest that free radical injury may promote myocardial decompensation. However, there are no studies in humans correlating the severity of heart failure with increased free radical injury and antioxidants. METHODS: Fifty-eight patients with CHF and 19 control subjects were studied. In addition to complete clinical and echocardiographic evaluations, the prognosis of these patients was established by measuring the levels of soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2). Oxidative stress was evaluated by measuring plasma lipid peroxides (LPO), malondialdehyde (MDA), glutathione peroxidase (GSHPx) and vitamin E and C levels. RESULTS: The patients' age range, cause of heart failure and drug intake were comparable across the different classes of heart failure. Heart failure resulted in a significant increase in LPO (p < 0.005), MDA (p < 0.005), sTNF-R1 (p < 0.005) and sTNF-R2 (p < 0.005). There was a significant positive correlation between the clinical class of heart failure and LPO, MDA, sTNF-R1 and sTNF-R2 levels. There was an inverse correlation between GSHPx and LPO. With increased lipid peroxidation in patients with CHF, the levels of vitamin C decreased, but vitamin E levels were maintained. CONCLUSIONS: These data demonstrate a progressive increase in free radical injury and encroachment on antioxidant reserves with the evolution of heart failure; they also suggest that oxidative stress may be an important determinant of prognosis. The therapeutic benefit of administering antioxidant supplements to patients with CHF should be evaluated.

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				H. R Gosker, E. F. Wouters, G. J van der Vusse, and A. M. Schols Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives Am J Clin Nutr, May 1, 2000; 71(5): 1033 - 1047. [Abstract] [Full Text] [PDF]

				M. Khatta, B. S. Alexander, C. M. Krichten, M. L. Fisher, R. Freudenberger, S. W. Robinson, and S. S. Gottlieb The Effect of Coenzyme Q10 in Patients with Congestive Heart Failure Ann Intern Med, April 18, 2000; 132(8): 636 - 640. [Abstract] [Full Text] [PDF]

				C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]

				R. Sethi, N. Takeda, M. Nagano, and N. S. Dhalla Beneficial Effects of Vitamin E Treatment in Acute Myocardial Infarction Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(1): 51 - 58. [Abstract] [PDF]

				W. J. Paulus How are cytokines activated in heart failure? Eur J Heart Fail, December 17, 1999; 1(4): 309 - 312. [Full Text] [PDF]

				E. Gronda and E. Vitali Left ventricle assist systems: a possible alternative to heart transplantation for heart failure patients? Patient selection, techniques and benefit Eur J Heart Fail, December 17, 1999; 1(4): 319 - 325. [Full Text] [PDF]

				H. Li, J. A. Lawson, M. Reilly, M. Adiyaman, S.-W. Hwang, J. Rokach, and G. A. FitzGerald Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F2-isoprostanes in human urine PNAS, November 9, 1999; 96(23): 13381 - 13386. [Abstract] [Full Text] [PDF]

				N. Raina, J. Lamarre, C.-C. Liew, A. H. Lofti, and K. N. Jeejeebhoy Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E464 - E473. [Abstract] [Full Text] [PDF]

				G. Kojda and D. Harrison Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure Cardiovasc Res, August 15, 1999; 43(3): 652 - 671. [Full Text] [PDF]

				M. Flesch, C. Maack, B. Cremers, A. T. Baumer, M. Sudkamp, and M. Bohm Effect of {beta}-Blockers on Free Radical Induced Cardiac Contractile Dysfunction Circulation, July 27, 1999; 100(4): 346 - 353. [Abstract] [Full Text] [PDF]

				T. Munzel and D. G. Harrison Increased Superoxide in Heart Failure : A Biochemical Baroreflex Gone Awry Circulation, July 20, 1999; 100(3): 216 - 218. [Full Text] [PDF]

				J. Bauersachs, A. Bouloumie, D. Fraccarollo, K. Hu, R. Busse, and G. Ertl Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression : Role of Enhanced Vascular Superoxide Production Circulation, July 20, 1999; 100(3): 292 - 298. [Abstract] [Full Text] [PDF]

				W. F. Saavedra, N. Paolocci, M. E. St. John, M. W. Skaf, G. C. Stewart, J.-S. Xie, R. W. Harrison, J. Zeichner, D. Mudrick, E. Marban, et al. Imbalance Between Xanthine Oxidase and Nitric Oxide Synthase Signaling Pathways Underlies Mechanoenergetic Uncoupling in the Failing Heart Circ. Res., February 22, 2002; 90(3): 297 - 304. [Abstract] [Full Text] [PDF]

				G. D. Thomas, W. Zhang, and R. G. Victor Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions : Role of Oxidative Stress Circ. Res., April 27, 2001; 88(8): 816 - 823. [Abstract] [Full Text] [PDF]