From the Cardiology Section, Department of Medicine, Veterans
Administration Medical Center (B.B., Y.S., H.O., D.L.M.), Cardiovascular
Sciences (L.H.M.), and the Department of Cell Biology, Huffington Aging Center
(V.V.D., P.J.H.), Baylor College of Medicine, Houston, Tex; the Department of
Surgery, Medical University of South Carolina, Charleston (S.B.K., F.G.S.);
and the Texas Heart Institute, Houston, Tex (F.J.C.).
Background—Although patients with
heart failure express elevated circulating levels of tumor necrosis
factor-
Methods and Results—Osmotic infusion pumps containing either
diluent or TNF-
Conclusions—These studies suggest that
pathophysiologically relevant concentrations of
TNF-
© 1998 American Heart Association, Inc.
Basic Science Reports
Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-
Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats
(TNF-) in their peripheral circulation, the
structural and functional effects of circulating levels of
pathophysiologically relevant concentrations of
TNF- on the heart are not known. were implanted into the peritoneal cavity of rats.
The rate of TNF- infusion was titrated to obtain systemic levels of
biologically active TNF- comparable to those reported in patients
with heart failure (
80 to 100 U/mL), and the animals were examined
serially for 15 days. Two-dimensional
echocardiography was used to assess changes in left
ventricular (LV) structure (remodeling) and LV function.
Video edge detection was used to assess isolated cell mechanics, and
standard histological techniques were used to assess
changes in the volume composition of LV cardiac myocytes and the
extracellular matrix. The reversibility of cytokine-induced
effects was determined either by removal of the osmotic infusion pumps
on day 15 or by treatment of the animals with a soluble TNF-
antagonist (TNFR:Fc). The results of this study show that a
continuous infusion of TNF- led to a time-dependent depression in LV
function, cardiac myocyte shortening, and LV dilation that were at
least partially reversible by removal of the osmotic infusion pumps or
treatment of the animals with TNFR:Fc. are sufficient to mimic certain aspects of the
phenotype observed in experimental and clinical models of heart
failure.
Key Words: heart failure • remodeling • contractility • cytokines
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D. L. Mann Inflammatory Mediators and the Failing Heart: Past, Present, and the Foreseeable Future Circ. Res., November 29, 2002; 91(11): 988 - 998. [Abstract] [Full Text] [PDF]
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Y. Sun, J. Zhang, L. Lu, S. S. Chen, M. T. Quinn, and K. T. Weber Aldosterone-Induced Inflammation in the Rat Heart : Role of Oxidative Stress Am. J. Pathol., November 1, 2002; 161(5): 1773 - 1781. [Abstract] [Full Text] [PDF]
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R. Nishio, S. Sasayama, and A. Matsumori Left ventricular pressure-volume relationship in a murine model of congestive heart failure due to acute viral myocarditis J. Am. Coll. Cardiol., October 16, 2002; 40(8): 1506 - 1514. [Abstract] [Full Text] [PDF]
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R. M Smith, N. Suleman, J. McCarthy, and M. N Sack Classic ischemic but not pharmacologic preconditioning is abrogated following genetic ablation of the TNF{alpha} gene Cardiovasc Res, August 15, 2002; 55(3): 553 - 560. [Abstract] [Full Text] [PDF]
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S. Nemoto, J. G. Vallejo, P. Knuefermann, A. Misra, G. Defreitas, B. A. Carabello, and D. L. Mann Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the adult heart Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2316 - H2323. [Abstract] [Full Text] [PDF]
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 H. Jankala, C. J. P. Eriksson, K. K. Eklund, M. Harkonen, and T. Maki COMBINED CALCIUM CARBIMIDE AND ETHANOL TREATMENT INDUCES HIGH BLOOD ACETALDEHYDE LEVELS, MYOCARDIAL APOPTOSIS AND ALTERED EXPRESSION OF APOPTOSIS-REGULATING GENES IN RAT Alcohol Alcohol., May 1, 2002; 37(3): 222 - 228. [Abstract] [Full Text] [PDF]
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D. B. Sawyer and J. Loscalzo Myocardial Hibernation: Restorative or Preterminal Sleep? Circulation, April 2, 2002; 105(13): 1517 - 1519. [Full Text] [PDF]
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W. S. Bradham, G. Moe, K. A. Wendt, A. A. Scott, A. Konig, M. Romanova, G. Naik, and F. G. Spinale TNF-alpha and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1288 - H1295. [Abstract] [Full Text] [PDF]
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V. Adams, B. Nehrhoff, U. Spate, A. Linke, P. C Schulze, A. Baur, S. Gielen, R. Hambrecht, and G. Schuler Induction of iNOS expression in skeletal muscle by IL-1{beta} and NF{kappa}B activation: an in vitro and in vivo study Cardiovasc Res, April 1, 2002; 54(1): 95 - 104. [Abstract] [Full Text] [PDF]
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A. Yndestad, J. Kristian Damas, H. Geir Eiken, T. Holm, T. Haug, S. Simonsen, S. S. Froland, L. Gullestad, and P. Aukrust Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure Cardiovasc Res, April 1, 2002; 54(1): 175 - 182. [Abstract] [Full Text] [PDF]
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 T. R. Bernik, S. G. Friedman, M. Ochani, R. DiRaimo, L. Ulloa, H. Yang, S. Sudan, C. J. Czura, S. M. Ivanova, and K. J. Tracey Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway J. Exp. Med., March 18, 2002; 195(6): 781 - 788. [Abstract] [Full Text] [PDF]
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W. S. Bradham, B. Bozkurt, H. Gunasinghe, D. Mann, and F. G. Spinale Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective Cardiovasc Res, March 1, 2002; 53(4): 822 - 830. [Abstract] [Full Text] [PDF]
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S. Adamopoulos, J. Parissis, D. Karatzas, C. Kroupis, M. Georgiadis, G. Karavolias, J. Paraskevaidis, K. Koniavitou, A. J. S. Coats, and D. T. Kremastinos Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fasligand system in patients with chronic heart failure J. Am. Coll. Cardiol., February 20, 2002; 39(4): 653 - 663. [Abstract] [Full Text] [PDF]
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R. J. Scheubel, B. Bartling, A. Simm, R.-E. Silber, K. Drogaris, D. Darmer, and J. Holtz Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium: Fragile balance of myocyte survival? J. Am. Coll. Cardiol., February 6, 2002; 39(3): 481 - 488. [Abstract] [Full Text] [PDF]
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C G Densem, I V Hutchinson, N Yonan, and N H Brooks Tumour necrosis factor {alpha} gene polymorphism: a predisposing factor to non-ischaemic myocardial dysfunction? Heart, February 1, 2002; 87(2): 153 - 155. [Abstract] [Full Text] [PDF]
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 D.L. MANN The Yin/Yang of Innate Stress Responses in the Heart Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 363 - 370. [Abstract] [PDF]
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V. Stangl, G. Baumann, K. Stangl, and S. B Felix Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion Cardiovasc Res, January 1, 2002; 53(1): 12 - 30. [Abstract] [Full Text] [PDF]
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R. Sodian, M. Loebe, C. Schmitt, E. V. Potapov, H. Siniawski, J. Muller, H. Hausmann, H. R. Zurbruegg, Y. Weng, and R. Hetzer Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1942 - 1949. [Abstract] [Full Text] [PDF]
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M.-W. Hwang, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, M. Hara, T. Miyamoto, M. Touma, and S. Sasayama Neutralization of interleukin-1{beta} in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1546 - 1553. [Abstract] [Full Text] [PDF]
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E. J. Birks, N. Latif, V. Owen, C. Bowles, L. E. Felkin, A. J. Mullen, A. Khaghani, P. J.R. Barton, J. M. Polak, J. R. Pepper, et al. Quantitative Myocardial Cytokine Expression and Activation of the Apoptotic Pathway in Patients Who Require Left Ventricular Assist Devices Circulation, September 18, 2001; 104 (2009): I-233 - I-240. [Abstract] [Full Text] [PDF]
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T. Kadokami, C. Frye, B. Lemster, C. L. Wagner, A. M. Feldman, and C. F. McTiernan Anti-Tumor Necrosis Factor-{alpha} Antibody Limits Heart Failure in a Transgenic Model Circulation, September 4, 2001; 104(10): 1094 - 1097. [Abstract] [Full Text] [PDF]
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N. Sivasubramanian, M. L. Coker, K. M. Kurrelmeyer, W. R. MacLellan, F. J. DeMayo, F. G. Spinale, and D. L. Mann Left Ventricular Remodeling in Transgenic Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor Circulation, August 14, 2001; 104(7): 826 - 831. [Abstract] [Full Text] [PDF]
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J. K. Damas, L. Gullestad, H. Aass, S. Simonsen, J. G. Fjeld, L. Wikeby, T. Ueland, H. G. Eiken, S. S. Froland, and P.a. Aukrust Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin J. Am. Coll. Cardiol., July 1, 2001; 38(1): 187 - 193. [Abstract] [Full Text] [PDF]
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 E. Braunwald Congestive heart failure: a half century perspective Eur. Heart J., May 2, 2001; 22(10): 825 - 836. [PDF]
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