title: Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.
abstract: BACKGROUND
  Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive.
  
  
  RESULTS
  Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk.
  
  
  CONCLUSIONS
  Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC.
authors.forename: Ethan J
authors.initials: EJ
authors.lastname: Anderson
authors.forename: Jimmy T
authors.initials: JT
authors.lastname: Efird
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Davies
authors.forename: Wesley T
authors.initials: WT
authors.lastname: O'Neal
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Darden
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Thayne
authors.forename: Lalage A
authors.initials: LA
authors.lastname: Katunga
authors.forename: Linda C
authors.initials: LC
authors.lastname: Kindell
authors.forename: T Bruce
authors.initials: TB
authors.lastname: Ferguson
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Anderson
authors.forename: W Randolph
authors.initials: WR
authors.lastname: Chitwood
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Koutlas
authors.forename: J Mark
authors.initials: JM
authors.lastname: Williams
authors.forename: Evelio
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kypson
mesh_terms: D000328:Adult; D000368:Aged; D020517:Atrial Appendage / Q000201:enzymology* / Q000601:surgery; D001281:Atrial Fibrillation / Q000201:enzymology* / Q000209:etiology; D015415:Biomarkers / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016009:Chi-Square Distribution; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D015999:Multivariate Analysis; D009206:Myocardium / Q000201:enzymology*; D019255:NADPH Oxidases / Q000378:metabolism; D016017:Odds Ratio; D010084:Oxidation-Reduction; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D008995:Monoamine Oxidase; D019255:NADPH Oxidases; D005980:Glutathione Reductase; D005978:Glutathione
keywords: biomarkers; cardiopulmonary bypass; catecholamines; oxidative stress; post‐operative atrial fibrillation; redox; tachyarrhythmias