Serum heparan sulfate levels are elevated in endotoxemia

<p>Abstract</p> <p>Background</p> <p>Increased vascular permeability is a characteristic feature of sepsis which, in the past, has been ascribed exclusively to a malfunction of endothelial cells. However, recently it has become evident that the endothelial glycocalyx is of considerable importance concerning various aspects of vascular physiology, e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential components is characteristically traceable in blood, in case the endothelial glycocalyx is damaged or destroyed.</p> <p>Methods</p> <p>In 15 pigs we investigated whether the administration of endotoxin from gram-negative bacteria (Escherichia coli) results in increased serum levels of heparan sulfate, signalizing a shedding of the glycocalyx. In addition, markers of inflammation (white blood cell count, platelet count, tumour necrosis factor-α and interleukin-6) were evaluated over an observation period of 6 hours.</p> <p>Results</p> <p>Serum heparan sulfate concentrations significantly increased over time in the endotoxin group and were significantly elevated in comparison to the control group 6 hours after administration of endotoxin (p < 0.001). In the endotoxin group all markers of inflammation significantly changed during the time course.</p> <p>Conclusions</p> <p>The administration of bacterial endotoxin induced a significant rise in degradation products of the endothelial glycocalyx.</p

Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock

Multiple experimental and human trials have shown that microcirculatory alterations are frequent in sepsis. In this review, we discuss the various mechanisms that are potentially involved in their development and the implications of these alterations. Endothelial dysfunction, impaired inter-cell communication, altered glycocalyx, adhesion and rolling of white blood cells and platelets, and altered red blood cell deformability are the main mechanisms involved in the development of these alterations. Microcirculatory alterations increase the diffusion distance for oxygen and, due to the heterogeneity of microcirculatory perfusion in sepsis, may promote development of areas of tissue hypoxia in close vicinity to well-oxygenated zones. The severity of microvascular alterations is associated with organ dysfunction and mortality. At this stage, therapies to specifically target the microcirculation are still being investigated