Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock
Abstract Background Disruption 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...
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2021
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oai:doaj.org-article:b78f2c9b0af84ac4b2fcd961d98166312021-11-28T12:23:49ZEffects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock10.1186/s40635-021-00417-42197-425Xhttps://doaj.org/article/b78f2c9b0af84ac4b2fcd961d98166312021-11-01T00:00:00Zhttps://doi.org/10.1186/s40635-021-00417-4https://doaj.org/toc/2197-425XAbstract Background Disruption 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) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). 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. Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold 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 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 a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE. Conclusions Septic 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 registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020Klaus StahlUta Carola HillebrandYulia KiyanBenjamin SeeligerJulius J. SchmidtHeiko SchenkThorben PapeBernhard M. W. SchmidtTobias WelteMarius M. HoeperAgnes SauerMalgorzata WygreckaChristian BodeHeiner WedemeyerHermann HallerSascha DavidSpringerOpenarticleExtracorporeal treatmentDAMPPlasmapheresisHeparan sulfateHeparanaseMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENIntensive Care Medicine Experimental, Vol 9, Iss 1, Pp 1-16 (2021) |
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Extracorporeal treatment DAMP Plasmapheresis Heparan sulfate Heparanase Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 |
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Extracorporeal treatment DAMP Plasmapheresis Heparan sulfate Heparanase Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Klaus Stahl Uta Carola Hillebrand Yulia Kiyan Benjamin Seeliger Julius J. Schmidt Heiko Schenk Thorben Pape Bernhard M. W. Schmidt Tobias Welte Marius M. Hoeper Agnes Sauer Malgorzata Wygrecka Christian Bode Heiner Wedemeyer Hermann Haller Sascha David Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| description |
Abstract Background Disruption 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) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). 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. Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold 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 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 a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE. Conclusions Septic 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 registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020 |
| format |
article |
| author |
Klaus Stahl Uta Carola Hillebrand Yulia Kiyan Benjamin Seeliger Julius J. Schmidt Heiko Schenk Thorben Pape Bernhard M. W. Schmidt Tobias Welte Marius M. Hoeper Agnes Sauer Malgorzata Wygrecka Christian Bode Heiner Wedemeyer Hermann Haller Sascha David |
| author_facet |
Klaus Stahl Uta Carola Hillebrand Yulia Kiyan Benjamin Seeliger Julius J. Schmidt Heiko Schenk Thorben Pape Bernhard M. W. Schmidt Tobias Welte Marius M. Hoeper Agnes Sauer Malgorzata Wygrecka Christian Bode Heiner Wedemeyer Hermann Haller Sascha David |
| author_sort |
Klaus Stahl |
| title |
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| title_short |
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| title_full |
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| title_fullStr |
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| title_full_unstemmed |
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| title_sort |
effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock |
| publisher |
SpringerOpen |
| publishDate |
2021 |
| url |
https://doaj.org/article/b78f2c9b0af84ac4b2fcd961d9816631 |
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