title: Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.
abstract: Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (IKAS) are heterogeneously upregulated in failing hearts. We hypothesized thatIKASinfluences the location and stability of rotors during VF.
  
  
  
  Optical mapping was performed on 9 rabbit hearts with pacing-induced heart failure. The epicardial right ventricular and left ventricular surfaces were simultaneously mapped in a Langendorff preparation. At baseline and after apamin (100 nmol/L) infusion, the action potential duration (APD80) was determined, and VF was induced. Areas with a >50% increase in the maximum action potential duration (ΔAPD) after apamin infusion were considered to have a highIKASdistribution. At baseline, the distribution density of phase singularities during VF in highIKASdistribution areas was higher than in other areas (0.0035±0.0011 versus 0.0014±0.0010 phase singularities/pixel;P=0.004). In addition, high dominant frequencies also colocalized to highIKASdistribution areas (26.0 versus 17.9 Hz;P=0.003). These correlations were eliminated during VF after apamin infusion, as the number of phase singularities (17.2 versus 11.0;P=0.009) and dominant frequencies (22.1 versus 16.2 Hz;P=0.022) were all significantly decreased. In addition, reentrant spiral waves became unstable after apamin infusion, and the duration of VF decreased.
  
  
  
  TheIKAScurrent influences the mechanism of VF in failing hearts as phase singularities, high dominant frequencies, and reentrant spiral waves all correlated to areas of highIKAS. Apamin eliminated this relationship and reduced VF vulnerability.
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Dechun
authors.initials: D
authors.lastname: Yin
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Adonis Zhi-Yang
authors.initials: AZ
authors.lastname: Wu
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Chan
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Dongzhu
authors.initials: D
authors.lastname: Xu
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.).
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.affiliation: From the Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.Y., Y.-C.H., W.-C.T., A.Z.-Y.W., Z.J., Y.-H.C., D.X., N.Y., Z.C., S.-F.L., P.-S.C., T.H.E.); Department of Cardiology (D.Y.) and Department of Gynecological and Obstetric Ultrasound (N.Y.), First Affiliated Hospital of Harbin Medical University, China; Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei (Y.-C.H.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (W.-C.T.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (A.Z.-Y.W., S.-F.L.); Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China (Z.J.); Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C.); Department of Cardiology, Faculty of Medicine, University of Tsukuba, Japan (D.X.); and Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.). theveret@iu.edu.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Everett
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D011817:Rabbits; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin
keywords: apamin; electrophysiology; heart failure; potassium; ventricular fibrillation