The Endothelial Glycocalyx Protects Against Myocardial Edema

Abstract

Myocardial tissue edema attributable to increased microvascular fluid loss contributes to cardiac dysfunction after myocardial ischemia, cardiopulmonary bypass, hypertension, and sepsis. Recent studies suggest that carbohydrate structures on the luminal surface of microvascular endothelium are essential to prevent tissue edema. We carefully preserved these structures for visualization with electron microscopy, revealing that the rat myocardial capillary endothelial surface is coated with a 0.2-to 0.5-m-thick carbohydrate layer and that its degradation instantly results in notable myocardial tissue edema.

Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts

“…To degrade the glycocalyx in the coronary circulation, we infused hyaluronidase at a concentration of 500 U/ml in the LCx region for two subsequent 20-min periods. With a Q LCx of ϳ30 ml/min (Table 1) and infusion rate of 2 ml/min, the estimated concentration in the coronary circulation is comparable to the 25 U/ml that was used previously by van den Berg et al (26) in isolated rat hearts. In that study, the endotheliumassociated carbohydrate layer in capillaries, visualized by electron microscopy, was greatly reduced by 1-h perfusion with hyaluronidase in the medium and resulted in significant myocardial interstitial edema formation (26).…”

“…Intravital microscopic studies of cremaster tissue have suggested that adenosine affects capillary perfusion by limiting the effect of the glycocalyx on vascular resistance (3,12,21). The glycocalyx is the carbohydrate-rich matrix that lines the luminal surface of blood vessels and forms the true interface between the endothelium and flowing blood (6,24,26,30). Normally, flowing red blood cells and large dextrans are excluded from the glycocalyx in cremaster capillaries (6, 30, 31).…”

“…In anesthetized dogs, coronary pressure and flow were measured in the left circumflex artery, and reactive hyperemia was compared with the hyperemia induced by intracoronary injection of adenosine. To determine the influence of the glycocalyx, interventions were repeated after hyaluronidase treatment of the coronary vascular bed, which reduces glycocalyx structures and increases its porosity (6,26). It was hypothesized that maximal coronary conductance obtained during reactive hyperemia would be lower than during adenosine hyperemia in control conditions but that this difference would be smaller in case of a degraded glycocalyx.…”

Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx

“…Diminution of the glycocalyx leads to activation of coagulation, leukocyte and platelet adhesion and increases capillary permeability, leading to tissue oedema (van den Berg et al, 2003). Furthermore, ischaemia/ reperfusion impairs shear-stress mediated, endothelium (nitric oxide)-dependent coronary vasodilatation, contributing to low reflow, and leads to damage of the coronary endothelium (Bouchard and Lamontagne, 1999).…”

Microcirculatory dysfunction and tissue oxygenation in critical illness

“…Endothelial exposure to oxidative stress, oxidized lipoproteins,32, 33, 34 and hyperglycemia35 cause further glycocalyx injury which in turn give rise to profound changes in capillary flows and hematocrit 33, 36. The glycocalyx constitutes a fluid barrier, and degradation of the glycocalyx is hence associated with edema and capillary compression 37, 38…”