Abstract
BackgroundDisruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) against fresh frozen plasma might influence eGC related pathology.MethodsWe enrolled 20 norepinephrine dependent (NE > 0.4μg/kg/min) patients with early septic shock (onset < 12h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products such as heparan-sulfate (HS) and the eGC regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls.ResultsSDF demonstrated a marked decrease in eGC thickness in septic patients compared to healthy individuals (p=0.001). Circulating HS levels were increased more than six-fold compared to controls and decreased significantly following TPE (controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p<0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p<0.001). The Hpa-2 /Hpa-1 ratio was markedly reduced in septic patients before TPE but normalized after TPE (controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p=0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p<0.001). Ex vivo stimulation of endothelial cells with serum from septic patients induced eGC damage that could be attenuated with serum post TPE.ConclusionsSeptic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency.Trial registrationclinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020
INTERACTION OF ENDOTHELIAL GLYCOCALYX WITH HEMODYNAMIC AND METABOLIC RESPONSE IN PATIENTS WITH SEPTIC SHOCK AND IN CARDIOSURGICAL INTERVENTIONS USING CARDIOPULMONARY BYPASS
