Canine model of Brugada syndrome using regional epicardial cooling of the right ventricular outflow tract.
BACKGROUND
Myocardial cooling can induce J point elevation (Osborn wave) as seen on ECG of the Brugada syndrome by activating transient outward current (Ito) and causing a spike-and-dome configuration of the monophasic action potential (MAP) in the ventricular epicardium in isolated canine ventricular wedge preparations. We determined the effect of regional epicardial cooling of the right ventricular outflow tract (RVOT) on surface ECG and ventricular vulnerability in the dog.


RESULTS
In 12 dogs, a cooling device (20-mm diameter) was attached to the RVOT epicardium, and surface ECG, epicardial MAP, and endocardial MAP were recorded. Regional cooling (29.7 degrees C +/- 2.2 degrees C) elevated the J point from 0.05 +/- 0.06 mV to 0.12 +/- 0.11 mV and induced T wave inversion (from 0.02 +/- 0.12 mV to -0.27 +/- 0.20 mV) in lead V1 in association with "spike-and-dome" configuration of the epicardial MAP. Cooling prolonged MAP duration in the RVOT epicardium from 172 +/- 27 ms to 213 +/- 30 ms (P < 0.01) but not in the RV endocardium and increased transmural dispersion of MAP duration from 9 +/- 8 ms to 44 +/- 21 ms (P < 0.01). Cooling also prolonged the QT interval in lead V1 from 191 +/- 19 ms to 212 +/- 23 ms (P < 0.05), but not in lead V5, and increased spatial dispersion of QT interval from 7 +/- 5 ms to 20 +/- 10 ms (P < 0.01). QT interval in lead V1 correlated positively with MAP duration in the RVOT epicardium (r = 0.75). T wave amplitude in lead V1 correlated inversely with transmural dispersion of MAP duration in the RVOT (r =-0.74). Vagal nerve stimulation accentuated the cooling-induced changes. During cooling, ventricular fibrillation was induced by a single extrastimulus in 2 of 4 dogs, and additional vagal nerve stimulation during isoproterenol administration induced spontaneous ventricular fibrillation in one dog.


CONCLUSIONS
Localized epicardial cooling of the RVOT could be an in vivo experimental model of Brugada syndrome.
Nishida
Kunihiro
K
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Fujiki
Akira
A
Mizumaki
Koichi
K
Sakabe
Masao
M
Sugao
Masataka
M
Tsuneda
Takayuki
T
Inoue
Hiroshi
H
D000200:Action Potentials; D000818:Animals; D002037:Bundle-Branch Block / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000379:methods; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D010496:Pericardium / Q000503:physiopathology; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*