Abstract
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 actionsin vitro and proinflammatory effectsin 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 Ceactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-α, 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-α, 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.
Résumé
Objectif
On a démontré que l’amiodarone (AMIO), un médicament anti-arythmique très utilisé, réduit l’incidence de fibrillation auriculaire après la chirurgie cardiaque et qu’il exerce une action immunomodulatrice in vitro ainsi que des effets pronflammatoires in vivo. Cette étude a observé les propriétés immunomodulatrices de l’AMIO dans la réaction inflammatoire provoquée par la chirurgie cardiaque avec circulation extracorporelle (CEC).
Méthode
Dans cette étude à double insu et contrôlée par placebo, vingt patients devant subir un pontage aortocoronarien ont été randomisés à recevoir oralement soit un placebo, soit de l’AMIO 600 mg·jour-1 les sept jours précédant la chirurgie et 45 mg·h-1 en intraveineux durant les 48 h suivant l’opération. Les niveaux plasmatiques des marqueurs pro-inflammatoires suivants ont été comparés avant et après l’opération: protéine C-réactive (CRP), fibrinogène (FBG), facteur nécrosant des tumeurs (TNF)- α, interleukine (IL)-6 et protéine chimioattractive monocytaire (MCP1), et le marqueur antinflammatoire IL-10.
Résultats
Les niveaux plasmatiques de FBG avaient plus que doublé 96 h après le début de la chirurgie (augmentation par 2,2 ± 0,5 fois, P < 0,0001). De façon générale, la formation de FBG s’est accrue de façon significative dans le groupe AMIO (P = 0,048). La sécrétion de la MCP-1 a momentanément augmenté quatre heures après le début de la chirurgie (de 6,6 ± 4,5 fois), mais a rapidement diminué ensuite (P < 0,0001). Une tendance vers des concentrations plasmatiques de MCP-1 plus élevées a été observée dans le groupe AMIO (P = 0,13). Les niveaux plasmatiques de CRP, TNF-α, IL-6 et IL-10 se sont modifiés de façon significative durant le temps de l’étude, mais le traitement à l’AMIO ne les a pas influencés.
Conclusion
Dans le cas de la réaction inflammatoire provoquée par une chirurgie cardiaque avec CEC, nos données suggèrent que le traitement à l’AMIO est associé à une tendance sélective vers des propriétés pronflammatoires.
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Supported by the “Austrian Fonds zur Foerderung der Wissenschaftlichen Forschung” (Grant P 15152) ISRCTN33778807.
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Karth, G.D., Buberl, A., Nikfardjam, M. et al. Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions. Can J Anesth 54, 262–268 (2007). https://doi.org/10.1007/BF03022770
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DOI: https://doi.org/10.1007/BF03022770