Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model: high-resolution optical mapping study.
OBJECTIVE
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 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 micromol/l), pinacidil (2 micromol/l), and pilsicainide (5 micromol/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.
Aiba
Takeshi
T
Department of Cardiovascular Dynamics, Research Institute, National Cardiovascular Center, Suita, Japan.
Shimizu
Wataru
W
Hidaka
Ichiro
I
Uemura
Kazunori
K
Noda
Takashi
T
Zheng
Can
C
Kamiya
Atsunori
A
Inagaki
Masashi
M
Sugimachi
Masaru
M
Sunagawa
Kenji
K
D000200:Action Potentials; D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D004699:Endocardium; D006329:Heart Conduction System / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced; D006352:Heart Ventricles / Q000187:drug effects; D008012:Lidocaine / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D010496:Pericardium; D020110:Pinacidil / Q000009:adverse effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D016593:Terfenadine / Q000009:adverse effects; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology*
D002317:Cardiovascular Agents; D020110:Pinacidil; D016593:Terfenadine; D008012:Lidocaine; C042288:pilsicainide