{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:31:27Z","timestamp":1780763487722,"version":"3.54.1"},"reference-count":39,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:p> 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 \u03bcmol\/l: 2.5\u201315 pinacidil, 5.0 terfenadine, and 5.0\u201313 pilsicainide). Bradycardia at cycle length (CL) of 2,632 \u00b1 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 \u00b1 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. <\/jats:p>","DOI":"10.1152\/ajpheart.01259.2005","type":"journal-article","created":{"date-parts":[[2006,4,29]],"date-time":"2006-04-29T00:38:42Z","timestamp":1146271122000},"page":"H421-H428","source":"Crossref","is-referenced-by-count":37,"title":["T wave alternans in an in vitro canine tissue model of Brugada syndrome"],"prefix":"10.1152","volume":"291","author":[{"given":"Hiroshi","family":"Morita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas P.","family":"Zipes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lopshire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho T.","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-8932(04)77101-8"},{"key":"R2","unstructured":"Aiba T, Hidaka I, Shimizu W, Uemura K, Inagaki M, Sugimachi M, and Sunagawa K. Steep repolarization gradient is required for development of phase 2 reentry and subsequent ventricular tachyarrhythmias in a model of the Brugada syndrome: high-resolution optical mapping study (Abstract). 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