To examine the inhibition of IL-6 involved in the effect of colchicine in preventing the occurrence of POAF, we administered IL-6 to rats to determine whether the therapeutic eff ;ect of colchicine can be abolished by supplementation with IL-6. IL-6 was injected intraperitoneally at 8 h and 48 h after surgery. As shown in Fig. 6A, the IL-6 level in atria was significantly increased again on day 3 after the supplementation of IL-6. Meanwhile, supplementation with IL-6 markedly increased the total AF duration (Fig. 6B) and the probability of AF induction (Fig. 6C). Conduction in the atria was also assessed in spontaneously beating and stimulated hearts using multi-electrode array mapping (Fig. 6D–G). Consistent with our recent findings , SP rats treated with vehicle show severe disruption of conduction homogeneity as demonstrated by the increased inhomogeneity index. However, the inhomogeneity index decreased after treatment with colchicine but increased again after supplementation with IL-6. Of note, there was no significant difference in conduction velocity among groups. In addition, the phosphorylation of STAT3 also increased again after supplementation with IL-6 (Fig. 6H,I). These results suggest that colchicine prevents POAF by inhibiting the expression of IL-6.
Fig. 6. The supplementation of IL-6 reversed the therapeutic effect of colchicine in SP rats. A. ELISA IL-6 in the atria. B and C. The mean duration of AF episodes (B) and probability (C) of induced AF. D and E. Typical maps of spontaneous conduction (D) and paced rhythm in the left atrium (from red to blue, bars indicate total time the last measurement within one heartbeat). FeG. Quantification of conduction velocity and conduction heterogeneity index during sinus rhythm (F) and 7 Hz (G). H and I. Representative western blot (H) and quantification (I) of p-STAT3/STAT3. GAPDH was used as an internal control. Data are the means±SEM. A one-way ANOVA with Bonferroni’s post-hoc test. &&&P<0.001, &&P<0.01 vs. Colchicine; n = 4-8 rats for each group. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
Biomedicine & Pharmacotherapy
