Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts

Dechun Yin; Yu-Cheng Hsieh; Wei-Chung Tsai; Adonis Zhi-Yang Wu; Zhaolei Jiang; Yi-Hsin Chan; Dongzhu Xu; Na Yang; Changyu Shen; Zhenhui Chen; Shien-Fong Lin; Peng-Sheng Chen; Thomas H Everett 4th

doi:10.1161/CIRCEP.116.004434

Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts

Circ Arrhythm Electrophysiol. 2017 Feb;10(2):e004434. doi: 10.1161/CIRCEP.116.004434.

Authors

Affiliations

¹ 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.).
² 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.

Abstract

Background: Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents (I_KAS) are heterogeneously upregulated in failing hearts. We hypothesized that I_KAS influences the location and stability of rotors during VF.

Methods and results: 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 high I_KAS distribution. At baseline, the distribution density of phase singularities during VF in high I_KAS distribution 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 high I_KAS distribution 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.

Conclusions: The I_KAS current influences the mechanism of VF in failing hearts as phase singularities, high dominant frequencies, and reentrant spiral waves all correlated to areas of high I_KAS. Apamin eliminated this relationship and reduced VF vulnerability.

Keywords: apamin; electrophysiology; heart failure; potassium; ventricular fibrillation.

MeSH terms

Action Potentials / physiology
Animals
Apamin / pharmacology*
Cardiac Pacing, Artificial
Disease Models, Animal
Female
Heart Failure / physiopathology*
Rabbits
Small-Conductance Calcium-Activated Potassium Channels / drug effects*
Small-Conductance Calcium-Activated Potassium Channels / metabolism*
Up-Regulation
Ventricular Fibrillation / physiopathology*
Ventricular Fibrillation / prevention & control*

Substances

Small-Conductance Calcium-Activated Potassium Channels
Apamin

Abstract

MeSH terms

Substances

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