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Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions

[Rôle de l’amiodarone sur la réaction inflammatoire systémique provoquée par la chirurgie cardiaque : actions pro-inflammatoires]

Georg Delle Karth, MD^*, Anton Buberl, MD^*, Mariam Nikfardjam, MD^*, Brigitte Meyer, MD^*, Gregor Wollenek, MD, Michael Grimm, MD, Andrea Lassnigg, MD, Werner Brannath, PhD, Michael Hiesmayr, MD and Gottfried Heinz, MD^*

^* From the Departments of Cardiology,
Cardiac-Thoracic Surgery, and
Cardiac-Thoracic Anesthesia, and the
Core Unit for Medical Statistics and Informatics Section of Medical Statistics, Medical University of Vienna, Austria.

Address correspondence to: Dr. Georg Delle Karth, Universitaetsklinik fuer Innere Medizin II/Kardiologie, Medizinische Universitaet, Wien, Waehringer Guertel 18-20, 1090 Wien, Austria. Phone: ++ 43-1-40400 -4615; Fax: ++43-1-40400 -4216; E-mail: georg.delle-karth{at}meduniwien.ac.at

Purpose: 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)-, 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-, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment.

Conclusion: 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.