Document Detail


Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx.
MedLine Citation:
PMID:  18073553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Daniel Chappell; Matthias Jacob; Klaus Hofmann-Kiefer; Dirk Bruegger; Markus Rehm; Peter Conzen; Ulrich Welsch; Bernhard F Becker
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  107     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-12-12     Completed Date:  2008-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  776-84     Citation Subset:  AIM; IM    
Affiliation:
Clinic of Anesthesiology, Ludwig-Maximilians University Munich, Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology*
Blood Pressure / drug effects
Capillary Permeability / drug effects
Endothelium, Vascular / drug effects*
Extravasation of Diagnostic and Therapeutic Materials / metabolism
Exudates and Transudates / drug effects
Glucose / administration & dosage
Glycocalyx / drug effects*,  metabolism,  ultrastructure
Guinea Pigs
Heart / drug effects*,  physiology
Hetastarch / administration & dosage
Histamine / metabolism
Hydrocortisone / pharmacology*
Male
Microscopy, Electron
Oxidative Stress / drug effects
Plasma Substitutes / administration & dosage
Reperfusion Injury / complications
Time Factors
Tromethamine / administration & dosage
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Krebs-Henseleit solution; 0/Plasma Substitutes; 50-23-7/Hydrocortisone; 50-99-7/Glucose; 51-45-6/Histamine; 77-86-1/Tromethamine; 9005-27-0/Hetastarch

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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