Circulating proteoglycans and glycosaminoglycans during critical illness

Abstract: The endothelial glycocalyx is the carbohydrate rich inner layer of the blood vessels. Important components of the glycocalyx are the proteoglycans with their attached glycosaminoglycans. At this location these molecules contribute to the adhesion and transport of leucocytes to inflamed tissue, the anticoagulation as well as the transport of fluid across the vessel wall. All these functions are disturbed during severe sepsis. The present thesis aims at determining if these molecules are increased in concentration of septic patients and/or if the blood levels provide additional information useful in the management of these patients. We found that circulating levels of glycosaminoglycans, and in particular heparan sulphate and hyaluronic acid, main glycosaminoglycans on the vessel wall, were higher in in septic shock patients compared to control patients. Furthermore, the concentration was higher in the patients that did not survive the disease. These results indicate that analysis may be useful and that the increased level is probably due to shedding from the glycocalyx. Severe haemorrhage is accompanied with development of a systemic inflammatory reaction. We found increased plasma levels of heparan sulphate during haemorrhagic shock in the rat, indicating damage to the glycocalyx. Treatment of the blood loss with fresh frozen plasma, albumin or Ringer’s acetate had no significant difference in the release of heparan sulphate. Transcapillary escape rate for albumin was not affected by bleeding, indicating that the induced damage to the glycocalyx was insufficient to affect the permeability. In a mixed cohort of intensive care patients circulating levels of the proteoglycans syndecan-1 was increased compared to controls. No difference was detected between patients with different underlying conditions. This indicates that syndecan-1 release is a general consequence of critical illness that probably has limited value as a marker in clinical practice.