pci-32765 and Atrial-Remodeling

Ibrutinib is a novel antitumor drug that targets Bruton tyrosine kinase for treatment of chronic lymphocytic leukemia. Atrial fibrillation (AF) occurs in 5%-9% of patients during treatment, but the underlying mechanisms remain unclear.. The purpose of this study was to develop a mouse model of ibrutinib-induced AF and investigate its proarrhythmic mechanisms.. In C57BI/6 mice in the ibrutinib and control groups, ibrutinib (25 mg/kg/d) or vehicle (hydroxypropy1-β-cyclodextrin), respectively, was administered orally for 4 weeks. Transesophageal burst stimulation then was used to induced AF. To evaluate the underlying mechanism of AF, cardiac echocardiography was performed. Ca. Compared with the control group, the ibrutinib group showed (1) a higher incidence and longer duration of AF with transesophageal burst stimulation; (2) increased left atrial mass, as indicated by echocardiography; (3) significant myocardial fibrosis in the left atrium on Masson trichrome staining; (4) Ca. The present study established a mouse model of AF by oral administration of ibrutinib for 4 weeks. The arrhythmogenic mechanisms underlying this model likely are associated with structural remodeling and Ca

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Antineoplastic Agents; Atrial Fibrillation; Atrial Remodeling; Calcium; Calcium Signaling; Disease Models, Animal; Echocardiography; Heart Atria; Leukemia, Lymphocytic, Chronic, B-Cell; Mice; Myocytes, Cardiac; Piperidines; Pyrazoles; Pyrimidines