title: Endothelial dysfunction in the early postoperative period after major colon cancer surgery.
abstract: BACKGROUND
  Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively.
  
  
  METHODS
  Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four.
  
  
  RESULTS
  Preoperative RHI was 1.86 (1.64 - 2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations.
  
  
  CONCLUSIONS
  RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine - nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery.
  
  
  BACKGROUND
  NCT02344771.
authors.affiliation: Centre for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebækvej1, 4600 Koege, Denmark savb@regionsjaelland.dk.
authors.forename: S
authors.initials: S
authors.lastname: Ekeloef
authors.affiliation: Centre for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebækvej1, 4600 Koege, Denmark.
authors.forename: M H H
authors.initials: MH
authors.lastname: Larsen
authors.affiliation: Faculty of Health & Medical Sciences, University of Copenhagen, Ridebanevej 9, Frederiksberg 1870, Denmark.
authors.forename: A M V
authors.initials: AM
authors.lastname: Schou-Pedersen
authors.affiliation: Faculty of Health & Medical Sciences, University of Copenhagen, Ridebanevej 9, Frederiksberg 1870, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Center for Perioperative Optimization, Department of Surgery, Herlev University Hospital, Herlev Ringvej 75, Herlev 2730, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Centre for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebækvej1, 4600 Koege, Denmark.
authors.forename: I
authors.initials: I
authors.lastname: Gögenür
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D003110:Colonic Neoplasms / Q000503:physiopathology / Q000601:surgery*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D011183:Postoperative Complications / Q000503:physiopathology; D011446:Prospective Studies; D019210:Troponin I / Q000097:blood
chemical_list: D019210:Troponin I; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: cardiovascular optimisation; myocardial injury; non-cardiac surgery; perioperative complications