Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model - High-resolution optical mapping study
Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model - High-resolution optical mapping study
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DOI:
10.1016/j.jacc.2005.12.064
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发表时间:
2006-05-16
影响因子:
24
通讯作者:
Sunagawa, Kenji
中科院分区:
文献类型:
--
作者:
Aiba, Takeshi;Shimizu, Wataru;Sunagawa, Kenji
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 (Br-ugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome.METHODS We used high-resolution (256 x 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 mu mol/l), pinacidil (2 mu mol/l), and pilsicainide (5 mu mol/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 (GR(max): 176 +/- 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GR(max) 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. (J Am Coll Cardiol 2006;47:2074-85) (c) 2006 by the American College of Cardiology Foundation.