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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U2 - 10.1152/ajpheart.00355.2012
DO - 10.1152/ajpheart.00355.2012
M3 - Article
C2 - 22707561
AN - SCOPUS:84865792502
SN - 0363-6135
VL - 303
SP - H578-H586
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -