title: Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  In conclusion, colchicine allowed a significant reduction of infarct size in mice, improves hemodynamic parameters and decrease cardiac fibrosis.
authors.affiliation: Cardiology Department, University Hospital of Montpellier, Montpellier, France; PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Mariama
authors.initials: M
authors.lastname: Akodad
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Fauconnier
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sicard
authors.affiliation: Cardiology Department, University Hospital of Montpellier, Montpellier, France; PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Huet
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Blandel
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Bourret
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Santa Barbara
authors.affiliation: Cardiology Department, University Hospital of Montpellier, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Aguilhon
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Marion
authors.initials: M
authors.lastname: LeGall
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Hugon
authors.affiliation: PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lacampagne
authors.affiliation: Cardiology Department, University Hospital of Montpellier, Montpellier, France; PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France. Electronic address: francois.roubille@gmail.com.
authors.forename: François
authors.initials: F
authors.lastname: Roubille
mesh_terms: D000818:Animals; D003078:Colchicine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000627:therapeutic use
chemical_list: D050257:Tubulin Modulators; D003078:Colchicine