Journal Article

Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion

Daniel Chappell, Matthias Jacob, Klaus Hofmann-Kiefer, Markus Rehm, Ulrich Welsch, Peter Conzen and Bernhard F. Becker

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 83, issue 2, pages 388-396
Published in print July 2009 | ISSN: 0008-6363
Published online March 2009 | e-ISSN: 1755-3245 | DOI: http://dx.doi.org/10.1093/cvr/cvp097
Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion

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Aims

Antithrombin is an important inhibitor of the coagulation system, additionally exerting specific anti-inflammatory effects on endothelial cells. Healthy vascular endothelium is coated by the endothelial glycocalyx, diminution of which increases capillary permeability, e.g. after ischaemia. Antithrombin is known to infiltrate the glycocalyx, binding to glycosaminoglycans, and to preserve the glycocalyx after application tumour necrosis factor-α. We investigated the influence of antithrombin on glycocalyx subjected to ischaemia/reperfusion.

Methods and results

Isolated guinea pig hearts were perfused with Krebs–Henseleit buffer (KHB). Antithrombin was applied to achieve physiological levels (1 U/mL) before inducing 20 min of ischaemia (37°C). Hearts were reperfused for 20 min at constant flow (baseline perfusion pressure 70 cmH2O) with KHB or KHB plus 2 g% hydroxyethyl starch (130 kDa). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Post-ischaemic coronary release of syndecan-1 and heparan sulfate was quantified by ELISA. Hearts were perfusion-fixed to visualize the glycocalyx by electron microscopy. Ischaemia/reperfusion caused degradation of the glycocalyx, enhanced coronary perfusion pressure, and increased vascular permeability. Antithrombin significantly reduced post-ischaemic glycocalyx shedding, coronary perfusion pressure, coronary leak, and tissue oedema formation compared to untreated hearts. Additional application of colloid augmented these actions of antithrombin. Electron microscopy revealed a mostly intact glycocalyx after antithrombin treatment.

Conclusion

Antithrombin preserves the endothelial glycocalyx, sustaining the vascular barrier function and reducing interstitial oedema. The potentiated effect of colloid in these hearts suggests that the prevention of shedding should be of functional benefit also in vivo.

Keywords: Endothelial function; Ischaemia; Antithrombin; Glycocalyx; Vascular leak

Journal Article.  5614 words.  Illustrated.

Subjects: Cardiovascular Medicine

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