title: Colchicine suppresses atrial fibrillation in failing heart.
abstract: BACKGROUND
  This study aimed to investigate the mechanism by which colchicine suppresses atrial fibrillation (AF) in a rabbit heart failure (HF) model.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Rahul
authors.initials: R
authors.lastname: Singhal
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Eric
authors.initials: E
authors.lastname: Chong
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsiao
authors.affiliation: Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shuen-Hsin
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yung-Nan
authors.initials: YN
authors.lastname: Tsai
authors.affiliation: Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiovascular Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chiao-Po
authors.initials: CP
authors.lastname: Hsu
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yenn-Jiang
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Trung Le
authors.initials: TL
authors.lastname: Ha
authors.affiliation: Department of Biomedical Engineering, National Defence Medical Centre, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. Electronic address: cwchiou@isca.vghks.gov.tw.
authors.forename: Chuen-Wang
authors.initials: CW
authors.lastname: Chiou
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. Electronic address: epsachen@ms41.hinet.net.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D015153:Blotting, Western; D003078:Colchicine / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy*; D007473:Ion Channels / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007473:Ion Channels; D011506:Proteins; D012333:RNA, Messenger; D003094:Collagen; D017239:Paclitaxel; D003078:Colchicine
keywords: Atrial fibrillation; Colchicine; Heart failure; PI3K/AKT/eNOS; Taxol