Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model

Background: Inflammation is deeply involved in the pathophysiology of ischemia-reperfusion (I/R) lesions and ventricular remodeling due to an acute myocardial infarction (AMI). Colchicine as a pleiotropic anti-inflammatory molecule may exert cardioprotective effects under acute ischemia. Here, we aimed to evaluate the impact of colchicine on reperfusion injury in a mouse model. Method: Myocardial ischemia/reperfusion (I/R) injury was induced in C57BL/6 male mice, after 45 min ligation of the left coronary artery followed by reperfusion. 400 mu g/kg of colchicine or the vehicle was administrated intraperitoneally (i.p.) 25 min before the reperfusion (blinded administration). Mice were sacrificed at 24 h after the acute myocardial ischemia (AMI) and the infarct size was determined. Circulating level of troponin and cytokines profile were assessed 4 h after the AMI. An echocardiography was performed in a follow-up group mice, 48 h and 8 weeks after the AMI. Results: The infarct size was reduced in colchicine treated mice (39.8 +/- 3.5% versus 52.9 +/- 3.2%, p < 0.05). Troponin was significantly lower in the colchicine treated mice (7015.7 +/- 1423.7 pg/mL, n = 5 vs 30,723.7 +/- 7959.9 pg/mL in the placebo group, n = 6; p < 0.0001). Fibrosis was decreased in the Colchicine group (24.51 +/- 3.13% vs 11.38 +/- 2.46%, p = 0.03). In the follow-up group mice (n = 8), there were no differences between mice treated with placebo (n = 9) and mice treated with colchicine (n = 9) regarding to cardiac remodeling parameters but outflow approximated by the ITV was higher in the colchicine group. Conclusion: In conclusion, colchicine allowed a significant reduction of infarct size in mice, improves hemodynamic parameters and decrease cardiac fibrosis. (C) 2017 Elsevier B.V. All rights reserved.