title: A randomized controlled trial to prevent post-operative atrial fibrillation by antioxidant reinforcement.
abstract: OBJECTIVE
  This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of post-operative atrial fibrillation.
  
  
  BACKGROUND
  Therapy to prevent post-operative atrial fibrillation remains suboptimal. Although oxidative stress plays a key role in the pathogenesis of this arrhythmia, antioxidant reinforcement has produced controversial results.
  
  
  METHODS
  A total of 203 patients scheduled for on-pump cardiac surgery were randomized to placebo or supplementation with n-3 polyunsaturated fatty acids (2 g/day) (eicosapentaenoic acid:docosahexaenoic acid ratio 1:2), vitamin C (1 g/day), and vitamin E (400 IU/day). The primary outcome was the occurrence of post-operative atrial fibrillation. Secondary outcomes were the biomarkers related to oxidative stress and inflammation.
  
  
  RESULTS
  Post-operative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05).
  
  
  CONCLUSIONS
  This safe, well-tolerated, and low-cost regimen, consisting of n-3 polyunsaturated fatty acids plus vitamins C and E supplementation, favorably affected post-operative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation. (Prevention of Post-Operative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning; ISRCTN45347268).
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: rrodrigo@med.uchile.cl.
authors.forename: Ramón
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Korantzopoulos
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cereceda
authors.forename: René
authors.initials: R
authors.lastname: Asenjo
authors.forename: Jaime
authors.initials: J
authors.lastname: Zamorano
authors.forename: Eli
authors.initials: E
authors.lastname: Villalabeitia
authors.forename: Cristián
authors.initials: C
authors.lastname: Baeza
authors.forename: Rubén
authors.initials: R
authors.lastname: Aguayo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Castillo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carrasco
authors.forename: Juan G
authors.initials: JG
authors.lastname: Gormaz
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D019587:Dietary Supplements; D016903:Drug Monitoring; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018384:Oxidative Stress / Q000187:drug effects*; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control; D016896:Treatment Outcome; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D014810:Vitamin E; D001205:Ascorbic Acid
keywords: DHA; EPA; MDA; POAF; PUFA; ROS; antioxidants; docosahexaenoic acid; eicosapentaenoic acid; inflammation; malondialdehyde; n-3 fatty acids; oxidative stress; polyunsaturated fatty acid; post-operative atrial fibrillation; reactive oxygen species; vitamin C; vitamin E