title: Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx.
abstract: BACKGROUND
  Hydrocortisone protects against ischemia-reperfusion injury, reduces paracellular permeability for macromolecules, and is routinely applied in the prevention of interstitial edema. Healthy vascular endothelium is coated by the endothelial glycocalyx, diminution of which increases capillary permeability, suggesting that the glycocalyx is a target for hydrocortisone action.
  
  
  METHODS
  Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer. Hydrocortisone was applied in a stress dose (10 microg/ml) before inducing 20 min of ischemia (37 degrees C). Hearts were reperfused for 20 min at constant flow (baseline perfusion pressure, 70 cm H2O) with Krebs-Henseleit buffer or Krebs-Henseleit buffer plus 2 g% hydroxyethyl starch (130 kd). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Hearts were perfusion fixed to visualize the glycocalyx.
  
  
  RESULTS
  Ischemia-induced degradation of the glycocalyx enhanced coronary perfusion pressure (118.8 +/- 17.3 cm H2O) and increased vascular permeability (8 +/- 0.2 microl x min(-1) x cm H2O(-1) at baseline vs. 34 +/- 3.3 microl x min(-1) x cm H2O(-1) after reperfusion). Enzymatic digestion of the glycocalyx (heparinase) elicited similar effects. Hydrocortisone reduced postischemic oxidative stress, perfusion pressure (86.3 +/- 6.4 cm H2O), and transudate formation (11 +/- 0.6 microl x min(-1) x cm H2O(-1)). Applying colloid augmented this (70.6 +/- 5.6 cm H2O and 9 +/- 0.5 microl x min(-1) x cm H2O(-1)). Postischemic shedding of syndecan-1, heparan sulfate, and hyaluronan was inhibited by hydrocortisone, as was release of histamine from resident mast cells. Electron microscopy revealed a mostly intact glycocalyx after hydrocortisone treatment, but not after heparinase treatment.
  
  
  CONCLUSIONS
  Hydrocortisone preserves the endothelial glycocalyx, sustaining the vascular barrier and reducing interstitial edema. The effect of colloids suggests that prevention of postischemic rise in coronary resistance by hydrocortisone could also be based on alleviation of endothelial swelling. Stabilization of myocardial mast cells by hydrocortisone may account for the mitigated inflammatory affect of ischemia-reperfusion.
authors: Clinic of Anesthesiology, Ludwig-Maximilians University Munich, Munich, Germany.
authors: Daniel
authors: D
authors: Chappell
authors: Matthias
authors: M
authors: Jacob
authors: Klaus
authors: K
authors: Hofmann-Kiefer
authors: Dirk
authors: D
authors: Bruegger
authors: Markus
authors: M
authors: Rehm
authors: Peter
authors: P
authors: Conzen
authors: Ulrich
authors: U
authors: Welsch
authors: Bernhard F
authors: BF
authors: Becker
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism; D005122:Exudates and Transudates / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects; D010952:Plasma Substitutes / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000150:complications; D013997:Time Factors; D014325:Tromethamine / Q000008:administration & dosage
chemical_list: D000893:Anti-Inflammatory Agents; D006895:Hydroxyethyl Starch Derivatives; C074097:Krebs-Henseleit solution; D010952:Plasma Substitutes; D014325:Tromethamine; D006632:Histamine; D005947:Glucose; D006854:Hydrocortisone