Document Detail


Clinical features of and effects of angiotensin system antagonists on amiodarone-induced pulmonary toxicity.
MedLine Citation:
PMID:  19106010     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Amiodarone (AMD) is a strong antiarrhythmic drug but has severe side effects such as pulmonary toxicity. There are no indicators or drugs that can prevent the development of amiodarone-induced pulmonary toxicity (AIPT). METHODS: We collected data for 96 consecutive patients treated with AMD and analyzed clinical factors related to AIPT. In addition, we examined the effect of AMD and angiotensin II (Ang II) on human lung alveolar epithelial cells (AEC) and verified the protective efficacy of an Ang II type 1 receptor blocker (ARB) in vitro. RESULTS: During a follow-up period of 33.8+/-34.6 months, AIPT developed in 11 patients (11.5%). There were no differences in the dose of AMD, left ventricular ejection fraction, serum KL-6 and %DLCO level before starting AMD between patients with and those without AIPT. However, repeated episodes of congestive heart failure (CHF) were observed more frequently in patients with AIPT than in patients without AIPT (81.8% vs. 41.2%, P<0.011). In vitro examination, AMD progressively increased apoptosis of AEC and Ang II enhanced this effect of AMD (P<0.001). However, ARB inhibited the enhancement by Ang II of the AMD-induced apoptosis effect (P<0.001). Furthermore, patients with AIPT were administrated a lower dose of angiotensin system antagonists than were those without AIPT (P<0.05). CONCLUSIONS: The results indicate that Ang II induced by CHF increases the risk of AMD-induced pulmonary toxicity. An angiotensin-converting enzyme inhibitor or ARB should be given at a sufficient dose during AMD treatment.
Authors:
Akira Nikaido; Takeshi Tada; Kazufumi Nakamura; Masato Murakami; Kimikazu Banba; Nobuhiro Nishii; Soichiro Fuke; Satoshi Nagase; Satoru Sakuragi; Hiroshi Morita; Tohru Ohe; Kengo Fukushima Kusano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-23
Journal Detail:
Title:  International journal of cardiology     Volume:  140     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  328-35     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Amiodarone / adverse effects*
Angiotensin II / blood,  drug effects*,  pharmacology
Angiotensin II Type 1 Receptor Blockers / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Anti-Arrhythmia Agents / adverse effects*
Apoptosis / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Female
Heart Failure / blood
Humans
Logistic Models
Lung Diseases / chemically induced*,  prevention & control
Male
Middle Aged
Multivariate Analysis
Pneumocytes / drug effects
Pulmonary Alveoli / drug effects
Retrospective Studies
Risk Factors
Survival Analysis
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Anti-Arrhythmia Agents; 11128-99-7/Angiotensin II; 1951-25-3/Amiodarone

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