title: Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles.
abstract: It has been reported that blockade of the inward rectifier K(+) current (IK1) facilitates termination of ventricular fibrillation. We hypothesized that partial IK1 blockade destabilizes spiral wave (SW) re-entry, leading to its termination. Optical action potential (AP) signals were recorded from left ventricles of Langendorff-perfused rabbit hearts with endocardial cryoablation. The dynamics of SW re-entry were analyzed during ventricular tachycardia (VT), induced by cross-field stimulation. Intercellular electrical coupling in the myocardial tissue was evaluated by the space constant. In separate experiments, AP recordings were made using the microelectrode technique from right ventricular papillary muscles of rabbit hearts. Ba(2+) (10-50 μM) caused a dose-dependent prolongation of VT cycle length and facilitated termination of VT in perfused hearts. Baseline VT was maintained by a stable rotor, where an SW rotated around an I-shaped functional block line (FBL). Ba(2+) at 10 μM prolonged I-shaped FBL and phase-singularity trajectory, whereas Ba(2+) at 50 μM transformed the SW rotation dynamics from a stable linear pattern to unstable circular/cycloidal meandering. The SW destabilization was not accompanied by SW breakup. Under constant pacing, Ba(2+) caused a dose-dependent prolongation of APs, and Ba(2+) at 50 μM decreased conduction velocity. In papillary muscles, Ba(2+) at 50 μM depolarized the resting membrane potential. The space constant was increased by 50 μM Ba(2+) Partial IK1 blockade destabilizes SW rotation dynamics through a combination of prolongation of the wave length, reduction of excitability, and enhancement of electrotonic interactions, which facilitates termination of ventricular tachyarrhythmias.
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kushiyama
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and honjo@riem.nagoya-u.ac.jp.
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Niwa
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takanari
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takemoto
authors.affiliation: Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001145:Arrhythmias, Cardiac; D001464:Barium / Q000494:pharmacology*; D003452:Cryosurgery; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D000067268:Isolated Heart Preparation; D009206:Myocardium / Q000378:metabolism*; D061848:Optical Imaging; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000378:metabolism* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium
keywords: inward rectifier K+ current; optical mapping; spiral wave re-entry; ventricular tachycardia