Amiodarone minimizes experimental autoimmune myocarditis in rats.
Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.
Matsui
Shinobu
S
Department of Cardiology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
Zong
Zhi-Ping
ZP
Han
Jian-Feng
JF
Katsuda
Shogo
S
Yamaguchi
Nobuo
N
Fu
Michael L X
ML
D000638:Amiodarone / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D008297:Male; D009205:Myocarditis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew
D000638:Amiodarone