Arrhythmogenic Effects of Arsenic Trioxide in Patients With Acute Promyelocytic Leukemia and an Electrophysiological Study in Isolated Guinea Pig Papillary Muscles

元データ 2006-10-20 社団法人日本循環器学会

概要

Background Arsenic trioxide (As_2O_3) 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 As_2O_3. Methods and Results Standard 12-lead ECGs were monitored throughout As_2O_3 therapy in 20 APL patients. As_2O_3 (0.15mg/kg) significantly prolonged the corrected QT interval (QTc: 445±7 to 517±17ms, 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 As_2O_3 perfusion (350μmol/L). The action potential duration was prolonged (APD_<90>: 150±11 to 195±12ms at 60min, p<0.01, n=5) and perfusion of As_2O_3 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 As_2O_3 induced muscle contracture, after-contractions, triggered activities and electromechanical alternans. Tetrodotoxin or butylated hydroxytoluene partially prevented the As_2O_3-induced prolongation of APD. Conclusions The prolonged QTc and spatial heterogeneity are responsible for the As_2O_3-induced ventricular tachyarrhythmias. In addition to prolongation of the APD, cellular Ca^<2+> overload and lipid peroxidation might contribute to the electrophysiological abnormalities caused by As_2O_3.

著者

Osaki K Department Of Pathology Kurume University School Of Medicine
Satoh Hiroshi Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Ohnishi K Third Department Of Internal Medicine Hamamatsu University School Of Medicine
AMAGASAKI Taro Novartis Pharma Japan
NAITO Kensuke The Third Department of Internal Medicine, Hamamatsu University School of Medicine
KATOH Hideki Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
HAYASHI Hideharu Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Katoh Hideki Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Internal Medicine Iii Hamamatsu University School Of Medicine
Naito Kensuke The Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Okayama Kenichi Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Odagiri Keiichi Department Of Medicine Hamamatsu Red Cross Hospital
NAITO Kensuke Division of Hematology, Department of Medicine III, Hamamatsu University School of Medicine
OHNISHI Kazunori Division of Hematology, Department of Medicine III, Hamamatsu University School of Medicine
Takeshita Akihiro Laboratory Medicine, Hamamatsu University School of Medicine
Hayashi Hideharu Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Takeshita A The Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Tomida Akihiro 癌研究会癌化学療法センター
Terada Hajime Divisions Of Cardiology Department Of Internal Medicine Iii
Terada Hajime Department Of Medicine Iii Hamamatsu University Of Medicine
Ohnishi Kazunori Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Uehara Akihiko Divisions Of Cardiology Department Of Internal Medicine Iii
Uehara Akihiko Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Tomita Akihiro First Department Of Internal Medicine Nagoya University School Of Medicine
Yamazaki Keisuke Divisions of Cardiology, Department of Internal Medicine III
Sone Hirohito Department Of Nutrition Ochanomizu University
Ohnishi Kazunori Department Of Internal Medicine Hamamatsu University School Of Medicine
Omachi Ken Department Of Hematology And Oncology Tokai University School Of Medicine
Ochi Kensuke Laboratory Of Molecular Medicine Human Genome Center Institute Of Medical Science University Of Toky
Ohhashi Kyoichi Department Of Clinical Pharmacology And Therapeutics Hamamatsu University School Of Medicine
Takeshita Akihiro Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Takeshita Akihiro Department Of Medicine Iii Hamamatsu University School Of Medicine
Terada Hajime Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Odagiri Keiichi Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Ohashi Kyoichi Department Of Clinical Pharmacology And Therapeutics Hamamatsu University School Of Medicine
Takeshita Akihiro Hamamatsu Univ. School Of Medicine Shizuoka Jpn
Yamazaki Keisuke Divisions Of Cardiology Department Of Internal Medicine Iii
Ohashi K Third Department Of Internal Medicine Hamamatsu University School Of Medicine
Ohnishi Kazunori Cancer Center Hamamatsu University School Of Medicine
Uehara Akihiro 3rd Department Of Internal Medicine Hamamatsu University
Naito Kensuke Department Of Hematology Hamamatsu Medical Center
Tamura Amane Hamamatsu Univ. School Of Medicine Shizuoka Jpn

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