@article{oai:hama-med.repo.nii.ac.jp:00001849,
 author = {Yamazaki, Keisuke and Terada, Hajime and Satoh, Hiroshi and Naito, Kensuke and Takeshita, Akihiro and Uehara, Akihiko and Katoh, Hideki and Ohnishi, Kazunori and Hayashi, Hideharu},
 issue = {11},
 journal = {Circulation Journal},
 month = {Oct},
 note = {Background Arsenic trioxide (As2O3) is a new promising regimen for patients with a relapse of acute promyelocytic leukemia (APL), but causes life-threatening arrhythmias. This study aimed to investigate the incidence and mechanism of arrythmogenesis caused by As2O3. Methods and Results Standard 12-lead ECGs were monitored throughout As2O3 therapy in 20 APL patients. As2O3 (0.15 mg/kg) significantly prolonged the corrected QT interval (QTc: 445±7 to 517±17 ms, means±SE, p<0.01), and also increased the QTc dispersion and transmural dispersion of repolarization. Non-sustained ventricular tachycardias and torsades de pointes occurred in 4 and 1 patients, respectively. The action potentials and isometric contraction were measured in guinea pig papillary muscles during As2O3 perfusion (350μmol/L). The action potential duration was prolonged (APD90: 150±11 to 195±12 ms at 60 min, p<0.01, n=5) and perfusion of As2O3 in a low K+ solution with a low stimulation rate augmented the prolongation of APD, and provoked early after-depolarizations and triggered activities. The prolonged exposure to As2O3 induced muscle contracture, after-contractions, triggered activities and electromechanical alternans. Tetrodotoxin or butylated hydroxytoluene partially prevented the As2O3-induced prolongation of APD. Conclusions The prolonged QTc and spatial heterogeneity are responsible for the As2O3-induced ventricular tachyarrhythmias. In addition to prolongation of the APD, cellular Ca2+ overload and lipid peroxidation might contribute to the electrophysiological abnormalities caused by As2O3.},
 pages = {1407--1414},
 title = {Arrhythmogenic Effects of Arsenic Trioxide in Patients With Acute Promyelocytic Leukemia and an Electrophysiological Study in Isolated Guinea Pig Papillary Muscles},
 volume = {70},
 year = {2006}
}