Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions.
OBJECTIVE
Amiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actions in vitro and proinflammatory effects in vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB).


METHODS
In this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg day(-1) orally for seven days before surgery and 45 mg hr(-1) intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers C-reactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery.


RESULTS
Ninety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 +/- 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 +/- 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-alpha, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment.


CONCLUSIONS
In the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.
Karth
Georg Delle
GD
Universitaetsklinik fuer Innere Medizin II/Kardiologie, Medizinische Universitaet, Wien, Waehringer Guertel 18-20, 1090 Wien, Austria. georg.delle-karth@meduniwien.ac.at
Buberl
Anton
A
Nikfardjam
Mariam
M
Meyer
Brigitte
B
Wollenek
Gregor
G
Grimm
Michael
M
Lassnigg
Andrea
A
Brannath
Werner
W
Hiesmayr
Michael
M
Heinz
Gottfried
G
D000368:Aged; D000638:Amiodarone / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000889:Anti-Arrhythmia Agents; D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005340:Fibrinogen; D002097:C-Reactive Protein; D000638:Amiodarone