title: Endothelial hyperpermeability after cardiac surgery with cardiopulmonary bypass as assessed using an in vitro bioassay for endothelial barrier function.
abstract: BACKGROUND
  The mechanisms causing increased endothelial permeability after cardiopulmonary bypass (CPB) have not been elucidated. Using a bioassay for endothelial barrier function, we investigated whether endothelial hyperpermeability is associated with alterations in plasma endothelial activation and adhesion markers and can be attenuated by the use of pulsatile flow during CPB.
  
  
  METHODS
  Patients undergoing cardiac surgery were randomized to non-pulsatile (n=20) or pulsatile flow CPB (n=20). Plasma samples were obtained before (pre-CPB) and after CPB (post-CPB), and upon intensive care unit (ICU) arrival. Changes in plasma endothelial activation and adhesion markers were determined by enzyme-linked immunosorbent assay. Using electric cell-substrate impedance sensing of human umbilical vein endothelial monolayers, the effects of plasma exposure on endothelial barrier function were assessed and expressed as resistance.
  
  
  RESULTS
  Cardiopulmonary bypass was associated with increased P-selectin, vascular cell adhesion molecule-1, and von Willebrand factor plasma concentrations and an increase in the angiopoietin-2 to angiopoietin-1 ratio, irrespective of the flow profile. Plasma samples obtained after CPB induced loss of endothelial resistance of 21 and 23% in non-pulsatile and pulsatile flow groups, respectively. The negative effect on endothelial cell barrier function was still present with exposure to plasma obtained upon ICU admission. The reduction in endothelial resistance after exposure to post-CPB plasma could not be explained by CPB-induced haemodilution.
  
  
  CONCLUSIONS
  The change in the plasma fingerprint during CPB is associated with impairment of in vitro endothelial barrier function, which occurs irrespective of the application of a protective pulsatile flow profile during CPB.
  
  
  BACKGROUND
  NTR2940.
authors.affiliation: Department of Anesthesiology.
authors.forename: N J
authors.initials: NJ
authors.lastname: Koning
authors.affiliation: Department of Anesthesiology.
authors.forename: M A H
authors.initials: MA
authors.lastname: Overmars
authors.affiliation: Department of Anesthesiology.
authors.forename: C E
authors.initials: CE
authors.lastname: van den Brom
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research.
authors.forename: J
authors.initials: J
authors.lastname: van Bezu
authors.affiliation: Department of Anesthesiology.
authors.forename: L E
authors.initials: LE
authors.lastname: Simon
authors.affiliation: Department of Cardio-thoracic Surgery.
authors.forename: A B A
authors.initials: AB
authors.lastname: Vonk
authors.affiliation: Department of Intensive Care Medicine, VU University Medical Centre, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
authors.forename: A R J
authors.initials: AR
authors.lastname: Girbes
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research.
authors.forename: G P
authors.initials: GP
authors.lastname: van Nieuw Amerongen
authors.affiliation: Department of Anesthesiology c.boer@vumc.nl.
authors.forename: C
authors.initials: C
authors.lastname: Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods*; D002199:Capillary Permeability / Q000502:physiology*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow / Q000502:physiology; D011897:Random Allocation
keywords: capillary permeability; cardiopulmonary bypass; endothelium, vascular; haemodilution; pulsatile flow