Colchicine Improves Survival, Left Ventricular Remodeling, and Chronic Cardiac Function After Acute Myocardial Infarction

• Published in: Circulation Journal Vol. 81; no. 8; pp. 1174 - 1182
• Main Authors: Fujisue, Koichiro, Sugamura, Koichi, Kurokawa, Hirofumi, Matsubara, Junichi, Ishii, Masanobu, Izumiya, Yasuhiro, Kaikita, Koichi, Sugiyama, Seigo
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2017
• Subjects: Animals; Colchicine; Colchicine - pharmacology; Disease Models, Animal; Inflammasome; Inflammation; Male; Mice; Myocardial infarction; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Recovery of Function - drug effects; Ventricular Remodeling - drug effects; Myocardial infarction; Inflammasome; Inflammation; Colchicine
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-16-0949

Background:Several studies have reported that colchicine attenuated the infarct size and inflammation in acute myocardial infarction (MI). However, the sustained benefit of colchicine administration on survival and cardiac function after MI is unknown. It was hypothesized that the short-term treatment with colchicine could improve survival and cardiac function during the recovery phase of MI.Methods and Results:MI was induced in mice by permanent ligation of the left anterior descending coronary artery. Mice were then orally administered colchicine 0.1 mg/kg/day or vehicle from 1 h to day 7 after MI. Colchicine significantly improved survival rate (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%, P<0.01), left ventricular end-diastolic diameter (5.0±0.2 vs. 5.6±0.2 mm, P<0.05) and ejection fraction (41.5±2.1 vs. 23.8±3.1%, P<0.001), as assessed by echocardiogram compared with vehicle at 4 weeks after MI. Heart failure development as pulmonary edema assessed by wet/dry lung weight ratio (5.0±0.1 vs. 5.5±0.2, P<0.01) and B-type natriuretic peptide expression in the heart was attenuated in the colchicine group at 4 weeks after MI. Histological and gene expression analysis revealed colchicine significantly inhibited the infiltration of neutrophils and macrophages, and attenuated the mRNA expression of pro-inflammatory cytokines and NLRP3 inflammasome components in the infarcted myocardium at 24 h after MI.Conclusions:Short-term treatment with colchicine successfully attenuated pro-inflammatory cytokines and NLRP3 inflammasome, and improved cardiac function, heart failure, and survival after MI.