Shedding of the coronary endothelial glycocalyx: Effects of hypoxia/reoxygenation vs ischaemia/reperfusion

Abstract

Background. Vascular endothelium is covered by a glycocalyx. Damage to the glycocalyx after systemic inflammation or ischaemia/reperfusion contributes to increased vascular permeability and leucocyte adhesion. The underlying mechanisms leading to ischaemia/reperfusion-induced glycocalyx shedding are incompletely understood, in terms of lack of oxygen, absence of flow, or return of oxygen. Methods. Isolated guinea pig hearts perfused with KrebsHenseleit buffer at 37°C underwent 20 min of either stopped-flow ischaemia or hypoxic perfusion with subsequent reperfusion/reoxygenation (n=6 each). Hearts perfused with normoxic buffer served as time controls. Epicardial transudate was collected to assess coronary net fluid filtration, colloid extravasation, and histamine release by mast cells. Syndecan-1 and heparan sulphate were measured in coronary effluent, together with lactate, purines, and the release of mast-cell tryptase β. Additional hearts were perfusion-fixed to visualize the glycocalyx. Results. Both ischaemia and hypoxia with reperfusion/ reoxygenation resulted in significant increases in net fluid filtration (P<0.05) and release of syndecan-1 and heparan sulphate in coronary effluent. These effects were already seen with the onset of hypoxic perfusion. Histamine was released during hypoxia and reoxygenation and also reperfusion, as was tryptase β, and high concentrations of adenosine (>1 μmol litre -1, hypoxia group) and inosine (>7 μmol litre-1, ischaemia group) were measured in effluent (P<0.05). Damage to the coronary glycocalyx was evident upon electron microscopy. Conclusions. Both ischaemic and hypoxic hypoxia initiate glycocalyx degradation, promoting an increase in permeability. A contributing mechanism could be purine-mediated degranulation of resident mast cells, with liberated tryptase β acting as potential 'sheddase'. © The Author [2011]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.