title: The Biomechanical Effects of Resuscitation Colloids on the Compromised Lung Endothelial Glycocalyx.
abstract: The endothelial glycocalyx is an important component of the vascular permeability barrier, forming a scaffold that allows serum proteins to create a gel-like layer on the endothelial surface and transmitting mechanosensing and mechanotransduction information that influences permeability. During acute inflammation, the glycocalyx is degraded, changing how it interacts with serum proteins and colloids used during resuscitation and altering its barrier properties and biomechanical characteristics. We quantified changes in the biomechanical properties of lung endothelial glycocalyx during control conditions and after degradation by hyaluronidase using biophysical techniques that can probe mechanics at (1) the aqueous/glycocalyx interface and (2) inside the glycocalyx. Our goal was to discern the location-specific effects of albumin and hydroxyethyl starch (HES) on glycocalyx function.
  
  
  
  The effects of albumin and HES on the mechanical properties of bovine lung endothelial glycocalyx were studied using a combination of atomic force microscopy and reflectance interference contrast microscopy. Logistic regression was used to determine the odds ratios for comparing the effects of varying concentrations of albumin and HES on the glycocalyx with and without hyaluronidase.
  
  
  
  Atomic force microscopy measurements demonstrated that both 0.1% and 4% albumin increased the thickness and reduced the stiffness of glycocalyx when compared with 1% albumin. The effect of HES on glycocalyx thickness was similar to albumin, with thickness increasing significantly between 0.1% and 1% HES and a trend toward a softer glycocalyx at 4% HES. Reflectance interference contrast microscopy revealed a concentration-dependent softening of the glycocalyx in the presence of albumin, but a concentration-dependent increase in stiffness with HES. After glycocalyx degradation with hyaluronidase, stiffness was increased only at 4% albumin and 1% HES.
  
  
  
  Albumin and HES induced markedly different effects on glycocalyx mechanics and had notably different effects after glycocalyx degradation by hyaluronidase. We conclude that HES is not comparable with albumin for studies of vascular permeability and glycocalyx-dependent signaling. Characterizing the molecular and biomechanical effects of resuscitation colloids on the glycocalyx should clarify their indicated uses and permit a better understanding of how HES and albumin affect vascular function.
authors.affiliation: From the *Department of Bioengineering, University of Utah, Salt lake City, Utah; and †Department of Anesthesiology, University of Illinois Chicago, Chicago, Illinois.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Job
authors.forename: Ryan
authors.initials: R
authors.lastname: O'Callaghan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Hlady
authors.forename: Alexandra
authors.initials: A
authors.lastname: Barabanova
authors.forename: Randal O
authors.initials: RO
authors.lastname: Dull
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003102:Colloids; D004305:Dose-Response Relationship, Drug; D055119:Elastic Modulus; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D016015:Logistic Models; D008168:Lung / Q000098:blood supply*; D018625:Microscopy, Atomic Force; D008857:Microscopy, Interference; D016017:Odds Ratio; D010952:Plasma Substitutes / Q000494:pharmacology*; D012151:Resuscitation / Q000379:methods*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
chemical_list: D003102:Colloids; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D012710:Serum Albumin, Bovine; D006821:Hyaluronoglucosaminidase