The glycocalyx as a permeability barrier: basic science and clinical evidence

Abstract

Preclinical studies in animals and human clinical trials question whether the endothelial glycocalyx layer is a clinically important permeability barrier. Glycocalyx breakdown products in plasma mostly originate from 99.6-99.8% of the endothelial surface not involved in transendothelial passage of water and proteins. Fragment concentrations correlate poorly with in vivo imaging of glycocalyx thickness, and calculations of expected glycocalyx resistance are incompatible with measured hydraulic conductivity values. Increases in plasma breakdown products in rats did not correlate with vascular permeability. Clinically, three studies in humans show inverse correlations between glycocalyx degradation products and the capillary leakage of albumin and fluid.

Keywords: Anesthesia; Capillaries; Fluid kinetics; Glycocalyx; Human studies; Permeability; Translational research.

Fig. 1

A Historical model of the glycocalyx (left), based on electron micrographs, proposed that the endothelial glycocalyx covered the cell surface including the luminal opening of the intercellular junction and the neck of caveolae. B The contemporary model (right) suggests that the glycocalyx residing over the cell body is much thicker than originally proposed but does not appreciably cover the junctional opening or caveolae neck. In the contemporary model, junctional complexes like the adherens junction limits protein permeability rather than the glycocalyx. Modified from Reference [3]

Fig. 2

Inverse relationship between the plasma syndecan-1 concentration and the rate constant for capillary leakage of A infused fluid when 1.5 L of crystalloid solution was administered to males with a mean age of 72 years, and B albumin when 3 mL/kg of 20% albumin was infused in post-burn patients. Each point represents one infusion experiment. The kinetic constants (k₁₂ and k_b) were generated by volume kinetic analysis. Subplot A is derived from Reference [71], and subplot B was created based on data published in Reference [56]. Regressions were based on square-root-transformed plasma syndecan-1 concentrations measured (by the same laboratory) just before the infusions were initiated. Note the logarithmic scale in subplot B