title: Endothelial permeability following coronary artery bypass grafting: an observational study on the possible role of angiopoietin imbalance.
abstract: BACKGROUND
  Unresolved inflammation resulting in capillary leakage with endothelial barrier dysfunction is a major contributor to postoperative morbidity and mortality after coronary artery bypass graft (CABG). Angiopoietins (ANGs) are vascular growth factors, also mediating inflammation and disruption of the endothelium, thus inducing capillary leakage. We hypothesized that changes in the relative serum levels of ANG1 and ANG2 influence endothelial barrier function and perioperative morbidity after CABG.
  
  
  METHODS
  After approval and informed consent, serum samples (n = 28) were collected pre CABG surgery, 1, 6, and 24 h after aortic de-clamping. ANG1, ANG2, soluble ANG receptor TIE2 (sTIE2), and IL-6 serum concentrations were analyzed by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with patient serum and FITC-dextran permeability was assessed. Furthermore, ANG2 secretion of HPMECs was analyzed after incubation with IL-6-containing patient serum.
  
  
  RESULTS
  CABG induced an early and sustained increase of ANG2/ANG1 ratio (5-fold after 24 h compared to pre-surgery). These changes correlated with elevated serum lactate levels, fluid balance, as well as the duration of mechanical ventilation. Permeability of HPMECs significantly increased after incubation with post-surgery serum showing a marked shift of ANG2/ANG1 balance (18-fold) compared to serum with a less pronounced increase (6-fold). Furthermore, CABG resulted in increased IL-6 serum content. Pre-incubation with serum containing high levels of IL-6 amplified the ANG2 secretion by HPMECs; however, this was not influenced by blocking IL-6.
  
  
  CONCLUSIONS
  CABG affects the balance between ANG1 and ANG2 towards a dominance of the barrier-disruptive ANG2. Our data suggest that this ANG2/ANG1 imbalance contributes to an increased postoperative endothelial permeability, likewise being reflected by the clinical course. The results strongly suggest a biological effect of altered angiopoietin balance during cardiac surgery on endothelial permeability.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. thilbert@uni-bonn.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hilbert
authors.affiliation: Department of Cardiovascular Surgery, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Daniel.Duerr@ukb.uni-bonn.de.
authors.forename: Georg Daniel
authors.initials: GD
authors.lastname: Duerr
authors.affiliation: Department of Cardiovascular Surgery, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Marwan.Hamiko@ukb.uni-bonn.de.
authors.forename: Marwan
authors.initials: M
authors.lastname: Hamiko
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Stilla.Frede@ukb.uni-bonn.de.
authors.forename: Stilla
authors.initials: S
authors.lastname: Frede
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. Lynette.Rogers@nationwidechildrens.org.
authors.forename: Lynette
authors.initials: L
authors.lastname: Rogers
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Georg.Baumgarten@ukb.uni-bonn.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Andreas.Hoeft@ukb.uni-bonn.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. Markus.Velten@ukb.uni-bonn.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000097:blood / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000097:blood / Q000378:metabolism*; D001026:Coronary Artery Bypass / Q000401:mortality*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D010539:Permeability; D042787:Receptor, TIE-2 / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019344:Lactic Acid; D042787:Receptor, TIE-2