Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia.
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.
Rehm
Markus
M
Clinic of Anesthesiology, Ludwig-Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany. markus.rehm@med.uni-muenchen.de
Bruegger
Dirk
D
Christ
Frank
F
Conzen
Peter
P
Thiel
Manfred
M
Jacob
Matthias
M
Chappell
Daniel
D
Stoeckelhuber
Mechthild
M
Welsch
Ulrich
U
Reichart
Bruno
B
Peter
Klaus
K
Becker
Bernhard F
BF
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
D006497:Heparan Sulfate; D018799:Intercellular Adhesion Molecule-1; D053668:Syndecan-1; D019010:Vascular Cell Adhesion Molecule-1; C508241:SDC1 protein, human