Cytotoxicity of amiodarone in cultured human endothelial cells.

Abstract:

:As damage to the pulmonary vascular endothelium may be responsible for the lung toxicity of amiodarone, we evaluated the cytolytic toxicity of the drug in cultures of endothelial cells. Cells were cultured from human umbilical cord veins. Amiodarone caused a vacuolization of the cells with liberation of both lactate dehydrogenase (LDH) and angiotensin-converting enzyme (ACE) in the culture medium. These effect were both concentration and time dependent, and were correlated between them. The first toxic effects were shown as soon as 2 hours after contact with the drug and at 0.1 mg/ml, a concentration that can be reached in plasma of amiodarone-treated patients. A decrease of ACE activity in the cells was delayed to 24 hours and only with the 10 mg/ml concentration. This event correlated with cell death and detachment from the extracellular matrix. LDH increases corresponded to its isoenzymes 3 and 4. These data support the hypothesis of a direct toxic effect of amiodarone on the endothelium and show the need for evaluating LDH, total activity and isoenzymic profile, and ACE determinations in the plasma of patients treated with amiodarone for ischemic heart disease or arrhythmia.

journal_name

Cardiovasc Drugs Ther

authors

Baudin B,Bénéteau-Burnat B,Giboudeau J

doi

10.1007/BF00050996

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

557-60

issue

5

eissn

0920-3206

issn

1573-7241

journal_volume

10

pub_type

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