T wave alternans in an in vitro canine tissue model of Brugada syndrome.
Macroscopic T wave alternans (TWA) associated with increased occurrence of ventricular arrhythmias has been reported in patients with Brugada syndrome. However, the mechanisms in this syndrome are still unclear. We evaluated the hypothesis that TWA in Brugada syndrome was caused by the dynamic instability and heterogeneity of action potentials (APs) in the right ventricle. Using an optical mapping system, we mapped APs on the epicardium or transmural surfaces of 28 isolated and arterially perfused canine right ventricular preparations having drug-induced Brugada syndrome (in micromol/l: 2.5-15 pinacidil, 5.0 terfenadine, and 5.0-13 pilsicainide). Bradycardia at cycle length (CL) of 2,632 +/- 496 ms (n = 19) induced alternating deep and shallow T waves in the transmural electrocardiogram. Compared with the shallow T waves, deep T waves were associated with epicardial APs having longer durations and larger domes. Adjacent regions having APs with alternating domes, with constant domes, and without domes coexisted simultaneously in the epicardium and caused TWA. In contrast to the alternating epicardial APs, midmyocardial and endocardial APs did not change during TWA. Alternans could be terminated by rapid (CL: 529 +/- 168 ms, n = 7) or very slow (CL: 3,000 ms, n = 7) pacing. The heterogeneic APs during TWA augmented the dispersion of repolarization both within the epicardium and from the epicardium to the endocardium and caused phase 2 reentry. In this drug-induced model of Brugada syndrome, heterogeneic AP contours and dynamic alternans in the dome of right ventricular epicardial, but not midmyocardial or endocardial, APs caused TWA and heightened arrhythmogenicity in part by increasing the dispersion of repolarization.
Morita
Hiroshi
H
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zipes
Douglas P
DP
Lopshire
John
J
Morita
Shiho T
ST
Wu
Jiashin
J
D000200:Action Potentials; D000818:Animals; D002037:Bundle-Branch Block / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010496:Pericardium / Q000503:physiopathology*; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000503:physiopathology*