Research

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2006年07月18日

Remodeling of the Atrium in Hypertension: A Basis to Increased Susceptibility to Atrial Tachyarrhythmia?
高血圧時の心房モデリング:心房性頻脈性不整脈との関連性

日 時 2006年07月18日(火) 15:00 より 16:30 まで
講演者 Andrew F. James 先生
講演者所属 University of Bristol, UK
お問い合わせ先 岡田泰伸 (機能協関) (内線 7731)
要旨

The major research focus of our laboratory is cardiac electrophysiology and the basis to arrhythmia. Atrial fibrillation (AF), the most common arrhythmia (its incidence increasing with age), is associated with increased mortality. AF has many causes and its etiology is complex. Animal models, in which causes of AF are studied in isolation, have provided valuable insights into the mechanisms underlying the disease. However, while hypertension is the most prevalent risk factor for AF, to date there have been no reports of atrial remodeling in any animal model of hypertension. We have examined the remodeling of the left atrium (LA) associated with hypertension, using spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto control (WKY) at two ages; 12-weeks and 42- weeks. The incidence of LA tachyarrhythmia (AT) following burst pacing in excised perfused whole hearts was increased in 42-week SHR compared with their age-matched WKY controls and compared with the 12- week SHR, demonstrating the development of a substrate for arrhythmia with age in hypertensive animals. This increased susceptibility to AT was not associated with changes in LA effective refractory period. On the other hand, whole-cell Ca2+ currents in isolated LA myocytes showed evidence of remodeling. There was also evidence of LA structural remodeling in SHR: SHR LA were hypertrophied compared to WKY and showed evidence of fibrosis. In conclusion, this study provides the first evidence of atrial remodeling producing a substrate for AT in an animal model of hypertension. Our work on sex differences in ventricular repolarisation and drug-induced arrhythmia may also be presented in this seminar.