Systemic inflammatory response in cardiac surgery: possibilities of using colchicine

Aim. To evaluate manifestations of systemic inflammatory response (SIR) and the effect of the colchicine therapy on SIR severity in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) with extracorporeal circulation (EC).

Material and methods. This study included 100 patients aged 62+6.3 years with stable IHD and multivessel coronary atherosclerosis scheduled for CABG with EC. Patients of group 1 (n=50) were administered with a single dose of colchicine (Colchicum-Dispert) 500 µg 4 hours before surgery followed by 500 µg twice a day for 10 days after surgery. Patients of group 2 (n=50) received a standard treatment, including nonsteroid anti-inflammatory drugs after surgery. Severity of the inflammatory response was evaluated by measuring blood cytokines.

Results. In the postoperative period, patient of group 1 showed a tendency toward a lower incidence of pleurisy and heart rhythm disorders in the form of paroxysmal atrial fibrillation (AF) (p=0.18). Levels of the anti-inflammatory cytokines, interleukin-10 (IL-10) and interleukin-6 (IL-6), were significantly increased in both groups at 6 hours after surgery (p<0.05); at the same time, in group 1, IL-10 remained increased also at 10 days after surgery (р=0.0002). No significant time-related changes in the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), were observed. At 3 days post-CABG, there were significant increases in tissue inhibitors of matrix metalloprotease 1 (TIMP-1) (р<0.0001) and matrix metalloproteinase 9 (MMP-9) (р<0.001); at the same time, patients of group 1 had lower MMP-9 concentrations than patients of group 2 (p<0.05). At 10 days of postoperative period, these values were comparable with the background values. Increases in neopterin compared to preoperative values were found in both groups on days 3 and 10 after surgery (р <0.0001).

Conclusion. CABG with EC is associated with the activation of SIR. The colchicine therapy at a dose of 500 µg 4 hours prior to surgery and 500 µg twice a day for 10 days after surgery reduces manifestations of SIR, which is clinically evident as a tendency to reduced incidence of pleurisy and arrhythmias, and does not result in the development of serious complications. The dynamics of matrix metalloproteinases indicates that the colchicine treatment is promising for decreasing the risk of CHF progression and myocardial remodeling in patients with IHD. 

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