title: Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia.
abstract: BACKGROUND
  The astonishing thickness of the endothelial glycocalyx, which rivals that of endothelial cells in the microvasculature, was disclosed in the last 15 years. As already demonstrated, this structure plays a key role in the regulation of inflammation and vascular permeability.
  
  
  RESULTS
  Two components of the glycocalyx, syndecan-1 and heparan sulfate, were measured in arterial blood of 18 patients undergoing surgery of the ascending aorta with cardiopulmonary bypass (n=12 with and n=6 without deep hypothermic circulatory arrest) and of 14 patients undergoing surgery for infrarenal aortic aneurysm. Basal values of syndecan-1 (1.2 microg/dL) and heparan sulfate (590 microg/dL) of patients were similar to those of control subjects. Anesthesia and initiation of surgery caused no changes. Global ischemia with circulatory arrest (n=12) was followed by transient 42- and 10-fold increases in syndecan-1 and heparan sulfate, respectively, during early reperfusion (0 to 15 minutes). After regional ischemia of heart and lungs (cardiopulmonary bypass; n=6), syndecan-1 increased 65-fold, and heparan sulfate increased 19-fold. Infrarenal ischemia was followed by 15- and 3-fold increases, respectively (n=14). The early postischemic rises were positively correlated (r=0.76, P<0.001). Plasma concentrations of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 did not change. Circulating polymorphonuclear granulocytes and the level of postischemic heparan sulfate corresponded negatively. Immunohistochemical imaging and immunoassay of isolated hearts (guinea pig) substantiated syndecan-1 and heparan sulfate as components of the endothelial glycocalyx released into the coronary venous effluent. Electron microscopy revealed shedding of the glycocalyx after ischemia/reperfusion.
  
  
  CONCLUSIONS
  This study provides the first evidence in humans for shedding of the endothelial glycocalyx during ischemia/reperfusion procedures.
authors.affiliation: Clinic of Anesthesiology, Ludwig-Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany. markus.rehm@med.uni-muenchen.de
authors.forename: Markus
authors.initials: M
authors.lastname: Rehm
authors.forename: Dirk
authors.initials: D
authors.lastname: Bruegger
authors.forename: Frank
authors.initials: F
authors.lastname: Christ
authors.forename: Peter
authors.initials: P
authors.lastname: Conzen
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
authors.forename: Matthias
authors.initials: M
authors.lastname: Jacob
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappell
authors.forename: Mechthild
authors.initials: M
authors.lastname: Stoeckelhuber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welsch
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
authors.forename: Klaus
authors.initials: K
authors.lastname: Peter
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Becker
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000601:surgery / Q000648:ultrastructure; D001014:Aortic Aneurysm / Q000378:metabolism* / Q000473:pathology; D002315:Cardiopulmonary Bypass; D050792:Circulatory Arrest, Deep Hypothermia Induced; D003331:Coronary Vessels / Q000378:metabolism* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D019276:Glycocalyx / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D006497:Heparan Sulfate / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood* / Q000473:pathology; D015425:Myocardial Reperfusion; D053668:Syndecan-1; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D006497:Heparan Sulfate; D018799:Intercellular Adhesion Molecule-1; D053668:Syndecan-1; D019010:Vascular Cell Adhesion Molecule-1; C508241:SDC1 protein, human