Arrhythmogenic Effects of Arsenic Trioxide in Patients With Acute Promyelocytic Leukemia and an Electrophysiological Study in Isolated Guinea Pig Papillary Muscles
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概要
- 論文の詳細を見る
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.
- 社団法人日本循環器学会の論文
- 2006-10-20
著者
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Osaki K
Department Of Pathology Kurume University School Of Medicine
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Satoh Hiroshi
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Ohnishi K
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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AMAGASAKI Taro
Novartis Pharma Japan
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NAITO Kensuke
The Third Department of Internal Medicine, Hamamatsu University School of Medicine
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KATOH Hideki
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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HAYASHI Hideharu
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Katoh Hideki
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Internal Medicine Iii Hamamatsu University School Of Medicine
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Naito Kensuke
The Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Okayama Kenichi
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Odagiri Keiichi
Department Of Medicine Hamamatsu Red Cross Hospital
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NAITO Kensuke
Division of Hematology, Department of Medicine III, Hamamatsu University School of Medicine
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OHNISHI Kazunori
Division of Hematology, Department of Medicine III, Hamamatsu University School of Medicine
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Takeshita Akihiro
Laboratory Medicine, Hamamatsu University School of Medicine
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Hayashi Hideharu
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Takeshita A
The Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Tomida Akihiro
癌研究会癌化学療法センター
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Terada Hajime
Divisions Of Cardiology Department Of Internal Medicine Iii
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Terada Hajime
Department Of Medicine Iii Hamamatsu University Of Medicine
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Ohnishi Kazunori
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Uehara Akihiko
Divisions Of Cardiology Department Of Internal Medicine Iii
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Uehara Akihiko
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Tomita Akihiro
First Department Of Internal Medicine Nagoya University School Of Medicine
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Yamazaki Keisuke
Divisions of Cardiology, Department of Internal Medicine III
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Sone Hirohito
Department Of Nutrition Ochanomizu University
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Ohnishi Kazunori
Department Of Internal Medicine Hamamatsu University School Of Medicine
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Omachi Ken
Department Of Hematology And Oncology Tokai University School Of Medicine
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Ochi Kensuke
Laboratory Of Molecular Medicine Human Genome Center Institute Of Medical Science University Of Toky
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Ohhashi Kyoichi
Department Of Clinical Pharmacology And Therapeutics Hamamatsu University School Of Medicine
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Takeshita Akihiro
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Takeshita Akihiro
Department Of Medicine Iii Hamamatsu University School Of Medicine
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Terada Hajime
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Odagiri Keiichi
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Ohashi Kyoichi
Department Of Clinical Pharmacology And Therapeutics Hamamatsu University School Of Medicine
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Takeshita Akihiro
Hamamatsu Univ. School Of Medicine Shizuoka Jpn
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Yamazaki Keisuke
Divisions Of Cardiology Department Of Internal Medicine Iii
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Ohashi K
Third Department Of Internal Medicine Hamamatsu University School Of Medicine
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Ohnishi Kazunori
Cancer Center Hamamatsu University School Of Medicine
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Uehara Akihiro
3rd Department Of Internal Medicine Hamamatsu University
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Naito Kensuke
Department Of Hematology Hamamatsu Medical Center
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Tamura Amane
Hamamatsu Univ. School Of Medicine Shizuoka Jpn
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