N-Acetylcysteine and Postoperative Atrial Fibrillation: Comment

We read with interest the recent work of Amar et al.,1 with the editorial by Karamnov and Muehischlegel2 which demonstrated the feasibility and safety of an antioxidant, N-acetylcysteine, for the prevention of atrial fibrillation after thoracic surgery. We agree with Karamnov and Muehischlegel2 that an anti-inflammatory approach using antioxidants reduces NADPH oxidase activity for postoperative atrial fibrillation, a plausible strategy for prophylaxis.2 However, we have additional potential explanations for why there was no significant difference in the occurrence of postoperative atrial fibrillation in patients who did and did not receive perioperative N-acetylcysteine in the study of Amar et al.1N-Acetylcysteine is an l-cysteine prodrug and glutathione precursor that, via l-cysteine conversion, helps scavenge oxygen-derived free radicals and binds metal ions into complexes, resulting in oxidative stress reduction.3 However, as we showed in a previous study, which was done in rats and focused on the mesenteric artery, l-cysteine induces an oxygen-derived free radical, superoxide production mediated by NADPH oxidase in a high 95% oxygen condition.4 In contrast, it does not cause redox derangement in a 50% oxygen mixture.4 Therefore, the high oxygen exposure under one-lung ventilation during major thoracic surgery seems to cancel l-cysteine’s beneficial role as a radical scavenger and to add oxidative stress. Nevertheless, we do not see any information regarding the inspiratory oxygen fraction in the work of Amar et al.,1 and thus, N-acetylcysteine combined with a high oxygen condition during thoracic surgery may contribute to the results shown by Amar et al.1 Also, previous studies indicated that a membrane-bound NADPH oxidase is the primary source of oxidative stress in human atrial fibrillation,5 while inflammation (or cytokines) activates several subtypes of NADPH oxidase.6 However, there are no clinically specific inhibitors of membrane-bound NADPH oxidase.Support was provided solely from institutional and/or departmental sources.The authors declare no competing interests.