title: Hemolysis compromises nitric oxide-dependent vasodilatory responses in patients undergoing major cardiovascular surgery.
abstract: BACKGROUND
  The hemolytic products cell-free oxyhemoglobin (FHb) and arginase-1 reduce nitric oxide (NO) bioavailability by scavenging NO and by degrading the NO precursor arginine to ornithine, respectively. In this study we evaluated the relevance of hemolysis to NO-dependent blood flow in patients undergoing cardiovascular surgery.
  
  
  METHODS
  Plasma FHb, arginase-1, and amino acid concentrations were measured perioperatively. Forearm blood flow (FBF) responses to the intra-arterial administered NO-donor sodium nitroprusside (SNP) and the endothelium-dependent vasodilator acetylcholine (ACh) were measured by venous occlusion plethysmography.
  
  
  RESULTS
  When peak values plasma FHb and arginase-1 were found, vascular dilatation to SNP, but not ACh, was significantly reduced compared with 1 day postoperatively, when FHb had returned to baseline levels (p < 0.05). Interestingly, plasma FHb concentration was inversely correlated to FBF responses to SNP (r -0.93, p < 0.001). In contrast, the increase in arginase-1 was not biologically relevant as the ratio of plasma arginine to ornithine remained constant.
  
  
  CONCLUSIONS
  We conclude that hemolysis with concomitant release of FHb during cardiovascular surgery is associated with impaired NO-dependent forearm blood flow.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands. b.hanssen@maastrichtuniversity.nl).
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: Hanssen
authors.forename: Marcel C
authors.initials: MC
authors.lastname: van de Poll
authors.forename: Alfons J
authors.initials: AJ
authors.lastname: Houben
authors.forename: Iris C Vermeulen
authors.initials: IC
authors.lastname: Windsant
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Snoeijs
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobs
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000368:Aged; D000704:Analysis of Variance; D017545:Aortic Aneurysm, Thoracic / Q000601:surgery*; D001119:Arginase / Q000097:blood; D001120:Arginine / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006461:Hemolysis; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D009426:Netherlands; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage / Q000378:metabolism; D009952:Ornithine / Q000097:blood; D010108:Oxyhemoglobins / Q000378:metabolism; D010991:Plethysmography; D013997:Time Factors; D014656:Vascular Surgical Procedures / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020030:Nitric Oxide Donors; D010108:Oxyhemoglobins; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine; C574619:ARG1 protein, human; D001119:Arginase; D000109:Acetylcholine