17 research outputs found

    New therapeutic target for the non-electrophysiological signaling in atrial fibrosis and fibrillation such as inflammation

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    AbstractWe have experimentally established appropriate models of atrial fibrillation (AF) with atrial interstitial fibrosis. Two approaches were adopted. Firstly, left atrial fibrosis was induced by continuous infusion of angiotensin II (AII). In an electrophysiological study using isolated perfused heart, AF was easily induced following AII treatment. Repeated whole-body hyperthermia led to the induction of heat-shock protein 72, which resulted in attenuation of AII-induced left atrial fibrosis and suppression of AF inducibility. Secondly, atrial fibrosis was induced by pressure overload by abdominal aortic constriction (AAC). AAC enhanced left atrial expression of monocyte chemoattractant protein-1 and activity of matrix metalloproteinase-9. Treatment with pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, resulted in attenuation of pressure overload-induced left atrial fibrosis and suppression of AF inducibility. In the same AAC model, the effects of candesartan on gap junction remodeling were investigated. Connexin 43 (Cx43) of the left atria was firmly located in the intercalated disks in control rats. A progressive redistribution of Cx43 from the intercalated disk to the lateral surface (lateralization) was observed in AAC rats. Candesartan prevented left Cx43 lateralization. Thus, heat-shock proteins, pioglitazone, and candesartan could be novel therapeutic approaches to prevent atrial fibrosis and AF

    QT Interval Revisited —Not Just the Matter of “Interval,” but “Dynamics, Variability and Morphology” Matter!—

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    Recently, the effects of QT interval prolongation have received more attention among clinicians, industry, and official regulatory agencies. Some have advocated the total elimination or discontinuing development of drugs which prolong the QT interval. In this review, we will give a brief overview of the pathophysiology and the dynamic variability and morphology of the QT interval. From the view point of arrhythmogenesis, QT interval prolongation with increased heterogeneity of ventricular repolarization is critical. The problem is how to detect such an abnormal repolarization. To detect heterogeneity, a new index should be developed and validated, and it must incorporate QT variability and morphology of the T wave. The heart rate correction of the QT interval is also an important issue, and disclosing conflict-corrected QT intervals depend on the formulae used. Not just QT interval prolongation is important; what also matters is the heterogeneity of ventricular repolarization