Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination

Yoshio Takemoto, Hiroki Takanari, Haruo Honjo, Norihiro Ueda, Masahide Harada, Sara Kato, Masatoshi Yamazaki, Ichiro Sakuma, Tobias Opthof, Itsuo Kodama, Kaichiro Kamiya

Research output: Contribution to journalArticle

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Abstract

Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV 0 - D·κ (D, diffusion coefficient; LCV 0, LCV at κ = 0). CBX decreased LCV0 and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV0 and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm -1. SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume303
Issue number5
DOIs
Publication statusPublished - 01-09-2012
Externally publishedYes

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Gap Junctions
Carbenoxolone
Cryosurgery
Incidence
Ventricular Fibrillation
Ventricular Tachycardia
Action Potentials
Myocardium
Pharmacology
Rabbits
Muscles
Isolated Heart Preparation
rotigaptide

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Takemoto, Yoshio ; Takanari, Hiroki ; Honjo, Haruo ; Ueda, Norihiro ; Harada, Masahide ; Kato, Sara ; Yamazaki, Masatoshi ; Sakuma, Ichiro ; Opthof, Tobias ; Kodama, Itsuo ; Kamiya, Kaichiro. / Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination. In: American Journal of Physiology - Heart and Circulatory Physiology. 2012 ; Vol. 303, No. 5.
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abstract = "Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36{\%}, whereas RG increased it by 22-24{\%} (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV 0 - D·κ (D, diffusion coefficient; LCV 0, LCV at κ = 0). CBX decreased LCV0 and D by 27 ± 3 and 57 ± 3{\%}, respectively (n = 5; P < 0.01). RG increased LCV0 and D by 18 ± 3 and 54 ± 5{\%}, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm -1. SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4{\%} after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6{\%} after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.",
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Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination. / Takemoto, Yoshio; Takanari, Hiroki; Honjo, Haruo; Ueda, Norihiro; Harada, Masahide; Kato, Sara; Yamazaki, Masatoshi; Sakuma, Ichiro; Opthof, Tobias; Kodama, Itsuo; Kamiya, Kaichiro.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 303, No. 5, 01.09.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination

AU - Takemoto, Yoshio

AU - Takanari, Hiroki

AU - Honjo, Haruo

AU - Ueda, Norihiro

AU - Harada, Masahide

AU - Kato, Sara

AU - Yamazaki, Masatoshi

AU - Sakuma, Ichiro

AU - Opthof, Tobias

AU - Kodama, Itsuo

AU - Kamiya, Kaichiro

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV 0 - D·κ (D, diffusion coefficient; LCV 0, LCV at κ = 0). CBX decreased LCV0 and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV0 and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm -1. SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.

AB - Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV 0 - D·κ (D, diffusion coefficient; LCV 0, LCV at κ = 0). CBX decreased LCV0 and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV0 and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm -1. SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.

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