Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.
Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha 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-alpha 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-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha 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.
Moro
Cécile
C
Coeur and Nutrition, Laboratoire TIMC-PRETA, Domaine de la Merci, University of Grenoble, Grenoble, France.
Jouan
Marie-Gabrielle
MG
Rakotovao
Andry
A
Toufektsian
Marie-Claire
MC
Ormezzano
Olivier
O
Nagy
Norbert
N
Tosaki
Arpad
A
de Leiris
Joël
J
Boucher
François
F
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism*; D020257:Ventricular Remodeling
D016207:Cytokines