Submitted on July 10, 2007
Accepted on September 10, 2007
Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodelling
Cecile Moro1, Jouan Marie-Gabrielle2, Andry Rakotovao2, Marie Claire Toufektsian2, Olivier Ormezzano3, Norbert Nagy4, Arpad Tosaki4, Joel de Leiris2, and Francois Boucher2*
1 laboratoire TIMC - PRETA, UMR5525 - IFRT130, Universite Grenoble I, La Tronche, France
2 Laboratoire TIMC - PRETA, UMR5525 - IFRT130, Universite Grenoble I, La Tronche, France
3 Service de Cardiologie et Hypertension Arterielle, CHU Michallon, Grenoble, France
4 Dept. Pharmacology, University of Debrecen, Debrecen, Hungary, Hungary
* To whom correspondence should be addressed. E-mail: francois.boucher{at}ujf-grenoble.fr.
Previous studies have shown that one week 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 other cytokines than TNF- can also be involved.
Anaesthetized male Wistar rats were subjected to 1-hour coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8 and 10 post-ligation. Before sacrifice, 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 remodelling. The profile of cardiac cytokines was determined by ELISA and ChemiarrayTM on heart tissue extracts.
As expected, ischemia-reperfusion induced a progressive remodelling 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-, IL1-
, IL-6, CINC2, CINC3 and MIP3- was also observed in the myocardium of MI animals at day 8, whereas the expression of anti-inflammatory interleukines IL-4 and IL-10 remained unchanged.
These results suggest that over expression 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 remodelling.
