Amiodarone inhibits arterial thrombus formation and tissue factor translation.
BACKGROUND
In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation.


RESULTS
Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-alpha and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. Metabolic labeling confirmed that amiodarone inhibited TF protein translation.


CONCLUSIONS
Amiodarone impairs thrombus formation in vivo; in line with this, it inhibits TF protein expression and surface activity in human vascular cells. These pleiotropic actions occur within the range of amiodarone concentrations measured in patients, and thus may account at least in part for its beneficial effects in patients with coronary artery disease.
Breitenstein
A
A
Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland.
Stämpfli
S F
SF
Camici
G G
GG
Akhmedov
A
A
Ha
H R
HR
Follath
F
F
Bogdanova
A
A
Lüscher
T F
TF
Tanner
F C
FC
D000638:Amiodarone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002341:Carotid Artery Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D012333:RNA, Messenger; C440780:mono-N-desethylamiodarone; D013925:Thromboplastin; D000638:Amiodarone