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Educati<strong>on</strong>al Objectives:<br />

The Endothelial Glycocalyx: A New Target in Critical Illness<br />

Can Ince PhD<br />

2:15-2:30<br />

Wednesday, February 15<br />

Discuss the morphology, compositi<strong>on</strong> and physiology of the endothelial glycocalyx<br />

Present methods of assessing the presence of the glycocalyx<br />

Discuss the how the glycocalyx is compromised, its pathophysiological c<strong>on</strong>sequences and the factors which c<strong>on</strong>tribute<br />

to its shedding.<br />

C<strong>on</strong>tent Descripti<strong>on</strong>:<br />

The endothelial glycocalyx is an intraluminal layer of about 0.2µm covering the endothelial cells of blood vessels.<br />

It is a compressible gel-like layer c<strong>on</strong>sisting of a web-like structure of membrane-bound glycoproteins and<br />

proteoglycans.<br />

The endothelial glycocalyx exerts a wide array of protective effects for the vasculature via inhibiti<strong>on</strong> of coagulati<strong>on</strong><br />

and leucocyte adhesi<strong>on</strong>, c<strong>on</strong>tributing to anti-oxidant compounds, c<strong>on</strong>tributing to the vascular permeability<br />

barrier and by mediating shear stress-induced NO release. Dem<strong>on</strong>strating its presence and its compromise has<br />

been technically very challenging which why its presence and significance has <strong>on</strong>ly recently come to light. Its<br />

compromise is detected under vital or electr<strong>on</strong> microscopy or by the presence of comp<strong>on</strong>ents of the shredded<br />

glycocalyx in plasma. Its degradati<strong>on</strong> is partially sensitive to reactive oxygen species and disease states associated<br />

with activati<strong>on</strong> of oxidative stress such as diabetes and sepsis as well probably a host of other diseased states<br />

where inflammatory activati<strong>on</strong> and oxidative stress are present. The appreciati<strong>on</strong> of its presence and physiological<br />

functi<strong>on</strong> has led to a re-appraisal of the view of fluid resuscitati<strong>on</strong> as a means of treating hypovolemia and<br />

maintaining intraluminal volume. In this respect there has been a reappraisal of the understanding of Starlings<br />

principle in describing the effects of colloids. It is clear that future will be focused <strong>on</strong> protective strategies aimed<br />

at the glycocalyx as well as novel fluid taking the importance the glycocalyx into account. Methods under development<br />

using high resoluti<strong>on</strong> vital microscopy to assess the presence of the glycocalyx at the bedside may prove<br />

useful in this respect.<br />

Suggested Reading:<br />

Nieuwdorp M, Meuwese MC, van Lieshout MHP, Levi M, Meijers JCM, Ince C, Vink H, Kastelein JJP, Erik<br />

SG Stroes ESG (2009) TNF· inhibiti<strong>on</strong> dampens endotoxin-induced endothelial glycocalyx perturbati<strong>on</strong> and<br />

inflammatory effects in vivo. Atherosclerosis. 202(1):296-303.<br />

Nieuwdorp M, Meuwese MC, Hans L Mooij HL, Ince C, BroekhuizenLN, Kastelein JP, Stroes ESG, Vink H<br />

(2008) Measuring endothelial glycocalyx dimensi<strong>on</strong>s in humans: a novel tool to m<strong>on</strong>itor vascular vulnerability. J<br />

of Applied Physiol 104(3):845-52<br />

Nieuwdorp M, Mooij HL, Kro<strong>on</strong> J, Atasever B, Spaan JA, Ince C, Holleman F, Diamant M, Heine RJ, Hoekstra<br />

JB, Kastelein JJ, Stroes ES, Vink H. (2006) Endothelial glycocalyx damage coincides with microalbuminuria in<br />

type 1 diabetes. Diabetes. Apr;55(4):1127-32<br />

Vink H and Duling BR. Identificati<strong>on</strong> of distinct luminal domains for macromolecules, erythrocytes, and leukocytes<br />

within mammalian capillaries. Circ Res 79: 581-589, 1996.<br />

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