Low-dose colchicine prevents sympathetic denervation after myocardial ischemia-reperfusion: a new potential protective mechanism.

PURPOSE: To evaluate the impact of colchicine on sympathetic denervation after acute myocardial infarction (AMI). MATERIALS & METHODS: Ischemia/Reperfusion was induced in C57BL/6J male mice. Left coronary artery was ligated during 45 min followed by reperfusion. 400 µg/kg of colchicine or the placebo was administrated intraperitoneally 15 min before the reperfusion. RESULTS: Colchicine treatment significantly improved heart rate variability index after AMI. Colchicine prevented sympathetic denervation in the remote area (p = 0.04) but not in the scar area (p = 0.70). CONCLUSION: These results suggest promising protective pathway of colchicine after AMI.

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 45min ligation of the left coronary artery followed by reperfusion. 400µg/kg of colchicine or the vehicle was administrated intraperitoneally (i.p.) 25min before the reperfusion (blinded administration). Mice were sacrificed at 24h after the acute myocardial ischemia (AMI) and the infarct size was determined. Circulating level of troponin and cytokines profile were assessed 4h after the AMI. An echocardiography was performed in a follow-up group mice, 48h and 8weeks 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±1423.7pg/mL, n=5 vs 30,723.7±7959.9pg/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.