Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model. High-Resolution Optical Mapping Study

Takeshi Aiba, Wataru Shimizu, Ichiro Hidaka, Kazunori Uemura, Takashi Noda, Can Zheng, Atsunori Kamiya, Masashi Inagaki, Masaru Sugimachi, Kenji Sunagawa

Research output: Contribution to journalArticle

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Abstract

Objectives: We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome. Background: Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome. Methods: We used high-resolution (256 × 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 μmol/l), pinacidil (2 μmol/l), and pilsicainide (5 μmol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition. Results: Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GRmax: 176 ± 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GRmax was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases. Conclusions: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

Original languageEnglish
Pages (from-to)2074-2085
Number of pages12
JournalJournal of the American College of Cardiology
Volume47
Issue number10
DOIs
Publication statusPublished - May 16 2006
Externally publishedYes

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Brugada Syndrome
Ventricular Fibrillation
Premature Cardiac Complexes
Maintenance
Ventricular Tachycardia
Electrocardiography
Pericardium
Action Potentials
Pinacidil
Terfenadine
Endocardium
Canidae

ASJC Scopus subject areas

  • Nursing(all)

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Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model. High-Resolution Optical Mapping Study. / Aiba, Takeshi; Shimizu, Wataru; Hidaka, Ichiro; Uemura, Kazunori; Noda, Takashi; Zheng, Can; Kamiya, Atsunori; Inagaki, Masashi; Sugimachi, Masaru; Sunagawa, Kenji.

In: Journal of the American College of Cardiology, Vol. 47, No. 10, 16.05.2006, p. 2074-2085.

Research output: Contribution to journalArticle

Aiba, Takeshi ; Shimizu, Wataru ; Hidaka, Ichiro ; Uemura, Kazunori ; Noda, Takashi ; Zheng, Can ; Kamiya, Atsunori ; Inagaki, Masashi ; Sugimachi, Masaru ; Sunagawa, Kenji. / Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model. High-Resolution Optical Mapping Study. In: Journal of the American College of Cardiology. 2006 ; Vol. 47, No. 10. pp. 2074-2085.
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abstract = "Objectives: We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome. Background: Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome. Methods: We used high-resolution (256 × 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 μmol/l), pinacidil (2 μmol/l), and pilsicainide (5 μmol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition. Results: Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GRmax: 176 ± 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GRmax was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases. Conclusions: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.",
author = "Takeshi Aiba and Wataru Shimizu and Ichiro Hidaka and Kazunori Uemura and Takashi Noda and Can Zheng and Atsunori Kamiya and Masashi Inagaki and Masaru Sugimachi and Kenji Sunagawa",
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T1 - Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model. High-Resolution Optical Mapping Study

AU - Aiba, Takeshi

AU - Shimizu, Wataru

AU - Hidaka, Ichiro

AU - Uemura, Kazunori

AU - Noda, Takashi

AU - Zheng, Can

AU - Kamiya, Atsunori

AU - Inagaki, Masashi

AU - Sugimachi, Masaru

AU - Sunagawa, Kenji

PY - 2006/5/16

Y1 - 2006/5/16

N2 - Objectives: We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome. Background: Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome. Methods: We used high-resolution (256 × 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 μmol/l), pinacidil (2 μmol/l), and pilsicainide (5 μmol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition. Results: Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GRmax: 176 ± 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GRmax was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases. Conclusions: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

AB - Objectives: We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome. Background: Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome. Methods: We used high-resolution (256 × 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 μmol/l), pinacidil (2 μmol/l), and pilsicainide (5 μmol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition. Results: Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GRmax: 176 ± 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GRmax was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases. Conclusions: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

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