New insights into the pathological role of TNF-{alpha} in early cardiac dysfunction and subsequent heart failure after infarction in rats

• Published in: American journal of physiology. Heart and circulatory physiology 2004-07, Vol.287 (1), p.H340
• Main Authors: Berthonneche, C, Sulpice, T, Boucher, F, Gouraud, L, de Leiris, J, O'Connor, S. E, Herbert, J.-M, Janiak, P
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01210.2003

1 Université Joseph Fourier, Grenoble; and 2 Cardiovascular-Thrombosis Department, Sanofi-Synthelabo Research, Chilly-Mazarin, France Submitted 18 December 2003 ; accepted in final form 17 February 2004 A marked increase in plasma TNF- has been described in patients with chronic heart failure (CHF). Nevertheless, little is known about the direct role of this cytokine early after myocardial infarction (MI) and its possible effects on the subsequent development of CHF. Wistar rats were subjected to permanent in vivo coronary artery ligation. At 5, 7, and 9 days after MI, cardiac function, passive compliance of the left ventricle (LV), and cardiac geometry were evaluated. The same model was used to perform pharmacological studies 7 days and 10 wk after MI in rats treated with monomeric recombinant human soluble TNF- receptor type II (sTNF-RII, 40 µg/kg iv) or a placebo on day 3 . Maximal alterations of cardiac function and geometry occurred 7 days after MI, which correlated chronologically with a peak of cardiac and serum TNF- , as shown by immunohistochemistry and ELISA, respectively. sTNF-RII improved LV end-diastolic pressure under basal conditions and after volume overload 7 days and 10 wk after MI. Moreover, a significant leftward shift of the pressure-volume curve in the sTNF-RII-treated group 7 days after MI indicated a preservation of LV volume. Infarct expansion index was also significantly improved by sTNF-RII 7 days after MI ( P < 0.01). Nevertheless, 10 wk after MI, geometric indexes and passive pressure-volume curves were not significantly improved by the treatment. In conclusion, TNF- plays a major role in cardiac alterations 7 days after MI in rats and contributes to hemodynamic derangement, but not to cardiac remodeling, in subsequent CHF. myocardial infarction; hemodynamics; cardiac geometry Address for reprint requests and other correspondence: F. Boucher, Laboratoire Stress Cardiovasculaires et Pathologies Associées, BÂtiment Jean Roget-Domaine de la Merci, Faculté de Médecine et de Pharmacie, Université Joseph Fourier, 38706 La Tronche Cedex, France (E-mail: Francois.Boucher{at}ujf-grenoble.fr ).