Colchicine attenuates myocardia inflammatory response after acute myocardial infarction demonstrated by C-14-methionine imaging

Objectives: Colchicine is a substance with pleiotropic anti-inflammatory effect and has been used for treatment and prevention of gouty attacks etc. This anti-inflammatory effect might be cardioprotective after acute myocardial infarction. We previously demonstrated that methionine uptake after myocardial ischemia and reperfusion reflects macrophage infiltration (JNM 2013; 54: 431-6). This study aimed to explore how colchicine administration at 1 day or more after reperfusion affects myocardial inflammatory response using C-14-methionine in a rat model of severe ischemia and reperfusion.

Methods: The left coronary artery was occluded for 30 min followed by reperfusion. In control rats, 3 and 7 days after reperfusion, C-14-methionine (0.74 MBq) was injected 20 min before sacrifice. One min before sacrifice, the left coronary artery was re-occluded and Tc-99m-MIBI (150-180 MBq) was injected to verify the area at risk. In rat with colchicine, 0.4 mg/Kg/day of colchicine was intraperitoneally administered every day from 1 day after reperfusion to the day before methionine injection (Day 3 and day 7). Dual-tracer autoradiography of the left ventricular short axis slices was performed. The first autoradiographic exposure on an imaging plate was performed for 15-20 min to visualize the area at risk expressed by Tc-99m-MIBI distribution at 1 to 2 h after sacrifice. Three days later the second exposure was made for 1-2 weeks to visualize the methionine uptake. The methionine uptake ratio in an ischemic area was calculated by dividing the count density in an ischemic area by that of a normally perfused area.

Results: In control rats (n=12), methionine uptake ratios at day 3 and 7 were 1.85 ± 0.15 and 1.38 ± 0.13, respectively. With colchicine (n=12), methionine uptake was reduced significantly at both day 3 (1.59 ± 0.24, p< 0.05) and at day 7 (1.25 ± 0.098, p< 0.05). In colchicine, uptake area of methionine to area at risk was similar to control at day 3 (0.67 ± 0.077 (control) vs 0.65 ± 0.048 (with colchicine), P = ns) and at day7 (0.57 ± 0.15 (control) vs 0.58 ± 0.048 (colchicine), P = ns). Conclusions: Administration of colchicine after severe ischemia and reperfusion attenuated methionine uptake both at day 3 and day 7, suggesting suppression of macrophage infiltration after myocardial infarction. It is concluded that colchicine treatment would suppress inflammatory response after myocardial infarction and methionine imaging would be feasible to monitor the effectiveness of the therapy.