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Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice

Authors: Andreas Margraf, Jan M. Herter, Katharina Kühne, Anika Stadtmann, Thomas Ermert, Manuel Wenk, Melanie Meersch, Hugo Van Aken, Alexander Zarbock, Jan Rossaint

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice.

Methods

6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation.

Results

Both CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 μm vs. 1.39 ± 0.10 μm) and lung capillaries (0.81 ± 0.09 μm vs. 1.49 ± 0.12 μm).

Conclusions

These data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.
Appendix
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Literature
1.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10.CrossRefPubMed
2.
Wilhelms SB, Huss FR, Granath G, Sjoberg F. Assessment of incidence of severe sepsis in Sweden using different ways of abstracting International Classification of Diseases codes: difficulties with methods and interpretation of results. Crit Care Med. 2010;38(6):1442–9.CrossRefPubMed
3.
Rossaint J, Zarbock A. Pathogenesis of multiple organ failure in sepsis. Crit Rev Immunol. 2015;35(4):277–91.CrossRefPubMed
4.
Groeneveld AB, Teule GJ, Bronsveld W, van den Bos GC, Thijs LG. Increased systemic microvascular albumin flux in septic shock. Intensive Care Med. 1987;13(2):140–2.CrossRefPubMed
5.
Christ F, Gamble J, Gartside IB, Kox WJ. Increased microvascular water permeability in patients with septic shock, assessed with venous congestion plethysmography (VCP). Intensive Care Med. 1998;24(1):18–27.CrossRefPubMed
6.
7.
Hahn RG. Why crystalloids will do the job in the operating room. Anaesthesiol Intensive Ther. 2014;46(5):342–9.CrossRefPubMed
8.
Kruer RM, Ensor CR. Colloids in the intensive care unit. Am J Health Syst Pharm. 2012;69(19):1635–42.CrossRefPubMed
9.
10.
Mohamed EI, Bayoumi AM. Modeling combined transport of water and charged graded-size molecules across the glomerular capillary wall. Biochem Biophys Res Commun. 2010;396(3):590–5.CrossRefPubMed
11.
Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20):1901–11.CrossRefPubMed
12.
Tarbell JM, Cancel LM. The glycocalyx and its significance in human medicine. J Intern Med. 2016;280(1):97–113.CrossRefPubMed
13.
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345–59.CrossRefPubMedPubMedCentral
14.
Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012;40(4):840–8.CrossRefPubMed
15.
16.
17.
Huang X, Kong G, Li Y, Zhu W, Xu H, Zhang X, Li J, Wang L, Zhang Z, Wu Y, et al. Decitabine and 5-azacitidine both alleviate LPS induced ARDS through anti-inflammatory/antioxidant activity and protection of glycocalyx and inhibition of MAPK pathways in mice. Biomed Pharmacother. 2016;84:447–53.CrossRefPubMed
18.
Han S, Lee SJ, Kim KE, Lee HS, Oh N, Park I, Ko E, Oh SJ, Lee YS, Kim D, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med. 2016;8(335):335ra355.CrossRef
19.
Nordling S, Hong J, Fromell K, Edin F, Brannstrom J, Larsson R, Nilsson B, Magnusson PU. Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation. Thromb Haemost. 2015;113(6):1312–22.CrossRefPubMed
20.
21.
Reutershan J, Basit A, Galkina EV, Ley K. Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L807–15.CrossRefPubMed
22.
Zarbock A, Distasi MR, Smith E, Sanders JM, Kronke G, Harry BL, von Vietinghoff S, Buscher K, Nadler JL, Ley K. Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of acute lung injury (ALI). J Immunol. 2009;183(7):4715–22.CrossRefPubMedPubMedCentral
23.
Radu M, Chernoff J. An in vivo assay to test blood vessel permeability. J Vis Exp. 2013;73:e50062.
24.
Block H, Herter JM, Rossaint J, Stadtmann A, Kliche S, Lowell CA, Zarbock A. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med. 2012;209(2):407–21.CrossRefPubMedPubMedCentral
25.
Herter JM, Rossaint J, Block H, Welch H, Zarbock A. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling. Blood. 2013;121(12):2301–10.CrossRefPubMed
26.
Zarbock A, Lowell CA, Ley K. Spleen tyrosine kinase Syk is necessary for E-selectin-induced αLβ2 integrin-mediated rolling on intercellular adhesion molecule-1. Immunity. 2007;26(6):773–83.CrossRefPubMedPubMedCentral
27.
Rossaint J, Herter JM, Van Aken H, Napirei M, Doring Y, Weber C, Soehnlein O, Zarbock A. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood. 2014;123(16):2573–84.CrossRefPubMed
28.
Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt ZX, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012;18(8):1217–23.CrossRefPubMed
29.
Vink H, Duling BR. Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res. 1996;79(3):581–9.CrossRefPubMed
30.
Marechal X, Favory R, Joulin O, Montaigne D, Hassoun S, Decoster B, Zerimech F, Neviere R. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock. 2008;29(5):572–6.PubMed
31.
Pahwa R, Nallasamy P, Jialal I. Toll-like receptors 2 and 4 mediate hyperglycemia induced macrovascular aortic endothelial cell inflammation and perturbation of the endothelial glycocalyx. J Diabetes Complications. 2016;30(4):563–72.CrossRefPubMed
32.
Brettner F, von Dossow V, Chappell D. The endothelial glycocalyx and perioperative lung injury. Curr Opin Anaesthesiol. 2017;30(1):36–41.PubMed
33.
Job KM, O’Callaghan R, Hlady V, Barabanova A, Dull RO. The biomechanical effects of resuscitation colloids on the compromised lung endothelial glycocalyx. Anesth Analg. 2016;123(2):382–93.CrossRefPubMedPubMedCentral
34.
Vlodavsky I, Eldor A, Haimovitz-Friedman A, Matzner Y, Ishai-Michaeli R, Lider O, Naparstek Y, Cohen IR, Fuks Z. Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation. Invasion Metastasis. 1992;12(2):112–27.PubMed
35.
de la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, Danese S, Fiocchi C, Stern R. Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol. 2009;174(6):2254–64.CrossRefPubMedPubMedCentral
36.
Rossaint J, Zarbock A. Platelets in leucocyte recruitment and function. Cardiovasc Res. 2015;107(3):386–95.CrossRefPubMed
37.
Herter JM, Rossaint J, Zarbock A. Platelets in inflammation and immunity. J Thromb Haemost. 2014;12(11):1764–75.CrossRefPubMed
38.
Albeiroti S, Ayasoufi K, Hill DR, Shen B, de la Motte CA. Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation. Blood. 2015;125(9):1460–9.CrossRefPubMedPubMedCentral
39.
Levi M, Jonge E. Clinical relevance of the effects of plasma expanders on coagulation. Semin Thromb Hemost. 2007;33(8):810–5.CrossRefPubMed
40.
Rossaint J, Berger C, Kraft F, Van Aken H, Giesbrecht N, Zarbock A. Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation. Br J Anaesth. 2015;114(3):509–19.CrossRefPubMed
41.
Petri B, Phillipson M, Kubes P. The physiology of leukocyte recruitment: an in vivo perspective. J Immunol. 2008;180(10):6439–46.CrossRefPubMed
42.
Mulivor AW, Lipowsky HH. Role of glycocalyx in leukocyte-endothelial cell adhesion. Am J Physiol Heart Circ Physiol. 2002;283(4):H1282–91.CrossRefPubMed
43.
Constantinescu AA, Vink H, Spaan JA. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol. 2003;23(9):1541–7.CrossRefPubMed
44.
Chappell D, Heindl B, Jacob M, Annecke T, Chen C, Rehm M, Conzen P, Becker BF. Sevoflurane reduces leukocyte and platelet adhesion after ischemia-reperfusion by protecting the endothelial glycocalyx. Anesthesiology. 2011;115(3):483–91.CrossRefPubMed
45.
McDonald KK, Cooper S, Danielzak L, Leask RL. Glycocalyx degradation induces a proinflammatory phenotype and increased leukocyte adhesion in cultured endothelial cells under flow. PLoS One. 2016;11(12):e0167576.CrossRefPubMedPubMedCentral
46.
Balkamou X, Xanthos T, Stroumpoulis K, Moutzouris DA, Rokas G, Agrogiannis G, Demestiha T, Patsouris E, Papadimitriou L. Hydroxyethyl starch 6% (130/0.4) ameliorates acute lung injury in swine hemorrhagic shock. Anesthesiology. 2010;113(5):1092–8.CrossRefPubMed
47.
Huang CC, Kao KC, Hsu KH, Ko HW, Li LF, Hsieh MJ, Tsai YH. Effects of hydroxyethyl starch resuscitation on extravascular lung water and pulmonary permeability in sepsis-related acute respiratory distress syndrome. Crit Care Med. 2009;37(6):1948–55.CrossRefPubMed
48.
Keh D, Trips E, Marx G, Wirtz SP, Abduljawwad E, Bercker S, Bogatsch H, Briegel J, Engel C, Gerlach H, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016;316(17):1775–85.CrossRefPubMed
49.
Lygizos MI, Yang Y, Altmann CJ, Okamura K, Hernando AA, Perez MJ, Smith LP, Koyanagi DE, Gandjeva A, Bhargava R, et al. Heparanase mediates renal dysfunction during early sepsis in mice. Physiol Rep. 2013;1(6):e00153.CrossRefPubMedPubMedCentral
50.
Chappell D, Bruegger D, Potzel J, Jacob M, Brettner F, Vogeser M, Conzen P, Becker BF, Rehm M. Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx. Crit Care. 2014;18(5):538.CrossRefPubMedPubMedCentral
51.
Bruegger D, Jacob M, Rehm M, Loetsch M, Welsch U, Conzen P, Becker BF. Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts. Am J Physiol Heart Circ Physiol. 2005;289(5):H1993–9.CrossRefPubMed
52.
Bruegger D, Schwartz L, Chappell D, Jacob M, Rehm M, Vogeser M, Christ F, Reichart B, Becker BF. Release of atrial natriuretic peptide precedes shedding of the endothelial glycocalyx equally in patients undergoing on- and off-pump coronary artery bypass surgery. Basic Res Cardiol. 2011;106(6):1111–21.CrossRefPubMed
53.
Hahn RG. Must hypervolaemia be avoided? A critique of the evidence. Anaesthesiol Intensive Ther. 2015;47(5):449–56.PubMed
54.
Bagshaw SM, Chawla LS. Hydroxyethyl starch for fluid resuscitation in critically ill patients. Can J Anaesth. 2013;60(7):709–13.CrossRefPubMed
55.
Gillies MA, Habicher M, Jhanji S, Sander M, Mythen M, Hamilton M, Pearse RM. Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis. Br J Anaesth. 2014;112(1):25–34.CrossRefPubMed
56.
Leberle R, Ernstberger A, Loibl M, Merkl J, Bunz M, Creutzenberg M, Trabold B. Association of high volumes of hydroxyethyl starch with acute kidney injury in elderly trauma patients. Injury. 2015;46(1):105–9.CrossRefPubMed
57.
Schimmer RC, Urner M, Voigtsberger S, Booy C, Roth Z’Graggen B, Beck-Schimmer B, Schlapfer M. Inflammatory kidney and liver tissue response to different hydroxyethylstarch (HES) preparations in a rat model of early sepsis. PLoS One. 2016;11(3):e0151903.CrossRefPubMedPubMedCentral
58.
Schick MA, Baar W, Bruno RR, Wollborn J, Held C, Schneider R, Flemming S, Schlegel N, Roewer N, Neuhaus W, et al. Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation. PLoS One. 2015;10(9):e0137247.CrossRefPubMedPubMedCentral
Metadata
Title
6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice
Authors
Andreas Margraf
Jan M. Herter
Katharina Kühne
Anika Stadtmann
Thomas Ermert
Manuel Wenk
Melanie Meersch
Hugo Van Aken
Alexander Zarbock
Jan Rossaint
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1846-3

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