title: Clinical features of and effects of angiotensin system antagonists on amiodarone-induced pulmonary toxicity.
abstract: 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.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nikaido
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tada
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Masato
authors.initials: M
authors.lastname: Murakami
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Banba
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishii
authors.forename: Soichiro
authors.initials: S
authors.lastname: Fuke
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagase
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakuragi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
authors.forename: Kengo Fukushima
authors.initials: KF
authors.lastname: Kusano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056809:Alveolar Epithelial Cells / Q000187:drug effects; D000638:Amiodarone / Q000009:adverse effects*; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011650:Pulmonary Alveoli / Q000187:drug effects; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D000804:Angiotensin II; D000638:Amiodarone