Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium

Yuko S. Ishiguro, Haruo Honjo, Tobias Opthof, Yusuke Okuno, Harumichi Nakagawa, Masatoshi Yamazaki, Masahide Harada, Hiroki Takanari, Tomoyuki Suzuki, Mikio Morishima, Ichiro Sakuma, Kaichiro Kamiya, Itsuo Kodama

研究成果: Article

21 引用 (Scopus)

抄録

Background: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. Objective: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (INa and ICa,L), respectively, on SW reentry. Methods: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. Results: During constant stimulation, pilsicainide (3-5 μM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 μM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% ± 9% for 5 μM pilsicainide vs. 22% ± 9% for controls and 62% ± 10% for 3 μM verapamil vs. 22% ± 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 μM pilsicainide and 3 μM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% ± 2% vs. 29% ± 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. Conclusion: Blockade of either INa or ICa,L stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.

元の言語English
ページ(範囲)684-692
ページ数9
ジャーナルHeart Rhythm
6
発行部数5
DOI
出版物ステータスPublished - 01-05-2009
外部発表Yes

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Ventricular Tachycardia
Verapamil
Myocardium
Rabbits
Action Potentials
Cryosurgery
Anti-Arrhythmia Agents
pilsicainide
Sodium
Calcium
Muscles
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

これを引用

Ishiguro, Yuko S. ; Honjo, Haruo ; Opthof, Tobias ; Okuno, Yusuke ; Nakagawa, Harumichi ; Yamazaki, Masatoshi ; Harada, Masahide ; Takanari, Hiroki ; Suzuki, Tomoyuki ; Morishima, Mikio ; Sakuma, Ichiro ; Kamiya, Kaichiro ; Kodama, Itsuo. / Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium. :: Heart Rhythm. 2009 ; 巻 6, 番号 5. pp. 684-692.
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title = "Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium",
abstract = "Background: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. Objective: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (INa and ICa,L), respectively, on SW reentry. Methods: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. Results: During constant stimulation, pilsicainide (3-5 μM) caused a frequency-dependent decrease of conduction velocity (CV; by 20{\%}-54{\%} at 5 Hz) without affecting action potential duration (APD). Verapamil (3 μM) caused APD shortening (by 16{\%} at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58{\%} ± 9{\%} for 5 μM pilsicainide vs. 22{\%} ± 9{\%} for controls and 62{\%} ± 10{\%} for 3 μM verapamil vs. 22{\%} ± 8{\%} for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 μM pilsicainide and 3 μM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2{\%} ± 2{\%} vs. 29{\%} ± 9{\%} for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. Conclusion: Blockade of either INa or ICa,L stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.",
author = "Ishiguro, {Yuko S.} and Haruo Honjo and Tobias Opthof and Yusuke Okuno and Harumichi Nakagawa and Masatoshi Yamazaki and Masahide Harada and Hiroki Takanari and Tomoyuki Suzuki and Mikio Morishima and Ichiro Sakuma and Kaichiro Kamiya and Itsuo Kodama",
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Ishiguro, YS, Honjo, H, Opthof, T, Okuno, Y, Nakagawa, H, Yamazaki, M, Harada, M, Takanari, H, Suzuki, T, Morishima, M, Sakuma, I, Kamiya, K & Kodama, I 2009, 'Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium', Heart Rhythm, 巻. 6, 番号 5, pp. 684-692. https://doi.org/10.1016/j.hrthm.2009.01.022

Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium. / Ishiguro, Yuko S.; Honjo, Haruo; Opthof, Tobias; Okuno, Yusuke; Nakagawa, Harumichi; Yamazaki, Masatoshi; Harada, Masahide; Takanari, Hiroki; Suzuki, Tomoyuki; Morishima, Mikio; Sakuma, Ichiro; Kamiya, Kaichiro; Kodama, Itsuo.

:: Heart Rhythm, 巻 6, 番号 5, 01.05.2009, p. 684-692.

研究成果: Article

TY - JOUR

T1 - Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium

AU - Ishiguro, Yuko S.

AU - Honjo, Haruo

AU - Opthof, Tobias

AU - Okuno, Yusuke

AU - Nakagawa, Harumichi

AU - Yamazaki, Masatoshi

AU - Harada, Masahide

AU - Takanari, Hiroki

AU - Suzuki, Tomoyuki

AU - Morishima, Mikio

AU - Sakuma, Ichiro

AU - Kamiya, Kaichiro

AU - Kodama, Itsuo

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Background: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. Objective: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (INa and ICa,L), respectively, on SW reentry. Methods: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. Results: During constant stimulation, pilsicainide (3-5 μM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 μM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% ± 9% for 5 μM pilsicainide vs. 22% ± 9% for controls and 62% ± 10% for 3 μM verapamil vs. 22% ± 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 μM pilsicainide and 3 μM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% ± 2% vs. 29% ± 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. Conclusion: Blockade of either INa or ICa,L stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.

AB - Background: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. Objective: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (INa and ICa,L), respectively, on SW reentry. Methods: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. Results: During constant stimulation, pilsicainide (3-5 μM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 μM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% ± 9% for 5 μM pilsicainide vs. 22% ± 9% for controls and 62% ± 10% for 3 μM verapamil vs. 22% ± 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 μM pilsicainide and 3 μM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% ± 2% vs. 29% ± 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. Conclusion: Blockade of either INa or ICa,L stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.

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