Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling

• Published in: American journal of physiology. Heart and circulatory physiology 2007-11, Vol.293 (5), p.H3014-H3019
• Main Authors: Moro, Cecile, Jouan, Marie-Gabrielle, Rakotovao, Andry, Toufektsian, Marie-Claire, Ormezzano, Olivier, Nagy, Norbert, Tosaki, Arpad, de Leiris, Joel, Boucher, Francois
• Format: Article
• Language: English
• Subjects: Animals; Cells; Cytokines; Cytokines - metabolism; Gene expression; Gene Expression Regulation; Heart attacks; Human health and pathology; Life Sciences; Male; Myocardial Infarction; Myocardial Infarction - complications; Myocardial Infarction - metabolism; Myocardial Reperfusion Injury; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - metabolism; Rats; Rats, Wistar; Rodents; Studies; Tissues; Tissues and Organs; Ventricular Dysfunction, Left; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - metabolism; Ventricular Remodeling
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00797.2007

1 Coeur and Nutrition, Laboratoire Techniques de l'Imagerie, de la Modélisation et de la Cognition-Physiologie Cardio-Respiratoire, Expérimentale, Therapeutique et Appliquée, Domaine de la Merci, University of Grenoble, and 2 Service de Cardiologie et Hypertension Arterielle, le Centre Hospitalier Universitaire, Grenoble, France; and 3 Department of Pharmacology, Health and Science Center, University of Debrecen, Debrecen, Hungary Submitted 10 July 2007 ; accepted in final form 10 September 2007 Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF- occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF- can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5 , 7 , 8 , and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF- , IL-1 , IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3 was also observed in the myocardium of myocardial ischemia (MI) animals at day 8 , whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling. myocardial ischemia; tumor necrosis factor- Address for reprint requests and other correspondence: François Boucher, Laboratoire TIMC-PRETA, UMR 5525, IFRT 130, Coeur & Nutrition, Domaine de la Merci, Bâtiment Jean Roget, Université Grenoble I, 38706 La Tronche Cedex, France (e-m