Major Revision? The endothelial glycocalyx is now two layers!

Layer upon layer: the functional consequences of disrupting the glycocalyx-endothelial barrier in vivo and in vitro. FitzRoy E. Curry Cardiovasc Res (2017) 113 (6): 559-561.

Fitzroy Curry seems to be the world’s go-to opinion on all things glycocalyx, and I was as usual delighted to find my own clinical ramblings being cited by the great man. In an Invited Editorial he observes

the concept of a uniform glycocalyx extending into the vessel lumen has led to the misconception that large volumes of the vascular space may be partitioned within the glycocalyx7(see ref2,8 for critique, and much lower estimates of the glycocalyx volume).

The guilty original work gave estimates in excess of a litre for a healthy glycocalyx layer (1), and I was first advised of the error by Charles Michel who has published his own critique. In my defense, let me remind everyone I am a clinician constructing a conceptual paradigm for other clinicians to make rational fluid therapy prescriptions and not a lab physiologist. More importantly, even if Nieuwdorp over estimated the endothelial glycocalyx volume three fold there is still enough volume there to make my simple paradigm credible.

I think it is now time for me to re-appraise my paradigm and update my teaching to convey the important fact that there are two layers to a glycocalyx. Curry writes

a layered structure with a dense branch-like inner layer (blue bushes) formed from heparan sulfate rich glycoproteins associated with the endothelial cell membrane (extending about 200 nm from the surface) and an outer gel-like layer, which is more porous (lightly hatched). The outer layer (up to 1 micron thick) contains adsorbed plasma proteins and other glycosaminoglycans such as hyaluronic acid. The inner layer forms the primary barrier to macromolecules (white arrow indicating limited access) and the outer layer forms the microstructure limiting access of red cells (shown) and leukocytes (not shown) to endothelial surface.

Our clinical paradigm survives, and the new detail provides lots of opportunity to find more clinical sequelae. Go for it!

  1. Nieuwdorp M, Meuwese MC, Mooij HL, Ince C, Broekhuizen LN, Kastelein JJ, Stroes ES, Vink H: Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability, J Appl Physiol 2008, 104:845-852

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