Abstract 12923: The Sustained Benefit of Short Term Treatment With Colchicine After Acute Myocardial Infarction

Abstract

Background: In acute myocardial infarction (MI), acute inflammation and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome are involved in cardiac damage, remodeling, and developing heart failure (HF). Several studies have reported that colchicine attenuated the infarct size and inflammation in MI. However, the sustained benefit of colchicine administration after MI on survival and cardiac function is unknown. We hypothesized that short-term treatment with colchicine could inhibit the cardiac inflammation and NLRP3 inflammasome, and improve survival and cardiac function during recovery phase of MI. Methods: Mice were induced MI by permanent ligation of the left anterior descending coronary artery. Mice randomly received 0.1 mg/kg/day colchicine or saline (control) orally from one hour to 7 days after MI. Results: Colchicine significantly improved survival rate compared with control at 4 weeks after MI (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%, P<0.01). Colchicine significantly improved 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) assessed by echocardiogram, and HF-development as pulmonary edema assessed by lung weight at 4 weeks after MI (P<0.05). Histological analysis revealed that colchicine significantly inhibited the infiltration of Gr-1-positive granulocytes and Iba-1-positive macrophages in the infarct area at 24 hours after MI, and significantly improved left ventricular scar expansion at 1 week after MI. In the infarcted myocardium at 24 hours after MI, colchicine significantly attenuated the MI-induced myeloperoxydase activity and the mRNA expression of tissue necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and pro-caspase-1 compared with control. Conclusions: Short-term treatment with colchicine successfully attenuated the infiltration of inflammatory cells, cytokines, and NLRP3 inflammasome in the infarcted myocardium, leading to improvement of adverse cardiac remodeling, cardiac function, HF-development, and survival.