Background This study aimed to investigate the mechanism by which colchicine suppresses atrial fibrillation (AF) in a rabbit heart failure (HF) model. Methods and results HF was induced by coronary ligation. Using the Langendorff perfusion system, monophasic action potentials were recorded in the left atrial appendage (LAA) of normal rabbits (n = 6) and HF rabbits (n = 6) treated with colchicine (100 μM) followed by colchicine (100 μM) plus paclitaxel (5 μM). Collagen content and mRNA and protein expression of ion channels through the PI3K/AKT/eNOS signaling pathway were evaluated in LAA of normal rabbits (n = 6) and HF rabbits treated with vehicle (n = 6) or colchicine (n = 6) intraperitoneal injection for 2 days. Colchicine decreased action potential duration (74.1 ± 2.6 vs 91.8 ± 3.3 ms, P < 0.001), effective refractory period, and maximum slope of the restitution curve in HF LAA. However, these effects were reversed by paclitaxel. The incidence of early afterdepolarizations, delayed afterdepolarizations, and AF inducibility was significantly lower after colchicine perfusion than at baseline or after colchicine plus paclitaxel perfusion. Cardiac function increased and LA fibrosis decreased after colchicine treatment. mRNA and protein expression of Kir2.1, Kv1.4, Kv1.5, Kv7.1, Cav1.2, and SERCA2a were upregulated after colchicine treatment, as was mRNA expression of PI3K, AKT, and eNOS. Conclusion Colchicine regulates ion channel gene expression and activates the PI3K/AKT/eNOS signaling pathway in HF rabbits, which may reverse atrial remodeling and suppress AF.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Singhal, R., Chang, S. L., Chong, E., Hsiao, Y. W., Liu, S. H., Tsai, Y. N., Hsu, C. P., Lin, Y. J., Lo, L. W., Ha, T. L., Chen, Y. C., Chen, Y-J., Chiou, C. W., & Chen, S. A. (2014). Colchicine suppresses atrial fibrillation in failing heart. International Journal of Cardiology, 176(3), 651-660. https://doi.org/10.1016/j.ijcard.2014.07.069