title: Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function.
abstract: BACKGROUND
  Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide.
  
  
  METHODS
  The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations.
  
  
  RESULTS
  The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates.
  
  
  CONCLUSIONS
  Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.
authors.affiliation: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, Victoria, Australia. p.myles@alfred.org.au
authors.forename: Paul S
authors.initials: PS
authors.lastname: Myles
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.forename: David R
authors.initials: DR
authors.lastname: McIlroy
authors.forename: Chung-Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Joel A
authors.initials: JA
authors.lastname: Symons
authors.forename: Shaohui
authors.initials: S
authors.lastname: Chen
mesh_terms: D000368:Aged; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009609:Nitrous Oxide / Q000009:adverse effects*; D018384:Oxidative Stress; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D009609:Nitrous Oxide