To restore a glycocalyx! Is there any opportunity?

Close metadata

Recommended articles:

Endothelial dysfunction and glycocalyx degradation in aortic surgery under moderate hypothermia and circulatory arrest. Russian Journal of Cardiology and Cardiovascular Surgery. 2024;(2):170-175

Endothelial glycocalyx is a layer enriched with glycoproteins, proteoglycans and glycosaminoglycans covering the entire vascular surface of endotheliocytes. Some components of glycocalyx are exfoliated by the bloodstream and aggressive biological agents and simultaneously replenished with blood glycosaminoglycans. Dynamic equilibrium of endothelial glycocalyx structure is disturbed by accelerated exfoliation of its elements (shear-stress) following hypoxia, hyper- and hypovolemia, hyperglycemia, enzymatic and microbial invasion. Glycocalyx damage leads to further endothelial lesion and endotheliitis underlying multiple critical conditions. Prevention of endothelial glycocalyx damage and its potential remodulation are perspective for the treatment of critical conditions. However, such methods and drugs are still not studied enough. At the same time, various experimental and clinical studies have been published over the last 20—25 years. According to these data, various modern drugs ensure own therapeutic effect apparently affecting the structure and integrity of endothelial glycocalyx. Remodulation of damaged glycocalyx via infusion of albumin and fresh frozen plasma was experimentally observed. At the same time, infusion of colloidal solutions (dextran, hydroxyethyl starches) had no similar effect. The ability of glucocorticoids to stabilize and prevent glycocalix damage has been obtained in clinical studies in neonates undergoing surgical interventions. Long-term use of sulodexide contributed to a 2-fold decrease of proteinuria and thickening of glycocalyx in renal capillaries in patients with diabetes mellitus. This review also considers the possibilities of other drugs in prevention of glycocalyx damage and its remodulation.

Keywords:

bleeding control

fresh frozen plasma

glycocalyx

protection

regeneration

Authors:

Sokologorsky S.V.

Sechenov First Moscow State Medical University

Ovechkin A.M.

Sechenov First Moscow State Medical University

ORCID: 0000-0002-3453-8699

Politov M.E.

Sechenov First Moscow State Medical University

Bulanova E.L.

Municipal Clinical Hospital No. 52

Received:

14.07.2021

Accepted:

05.10.2021

List of references:

Levick JR. Revision of the Starling principle: new views of tissue fluid balance. The Journal of Physiology. 2004;557(Pt 3):704. https://doi.org/10.1113/jphysiol.2004.066118
Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovascular Research. 2010;87(2):198-210. https://doi.org/10.1093/cvr/cvq062
Jeansson M, Haraldsson B. Morphological and functional evidence for an important role of the endothelial cell glycocalyx in the glomerular barrier. American Journal of Physiology. Renal Physiology. 2006;290(1):111-116. https://doi.org/10.1152/ajprenal.00173.2005
Steppan J, Hofer S, Funke B, Brenner T, Henrich M, Martin E, Weitz J, Hofmann U, Weigand MA. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix. The Journal of Surgical Research. 2011;165(1):136-141. https://doi.org/10.1016/j.jss.2009.04.034
Yarustovsky MB, Abramyan MB, Krotenko NP, Popov DA, Plyusch MG, Nazarova EI, Gordeev SL. Experience of use of endotoxin selective adsorption in patients with heavy sepsis after open-heart surgery. Anesteziologiya i reanimatologiya. 2014;3:39-46. (In Russ.).
Nieuwdorp M, Mooij HL, Kroon J, Atasever B, Spaan JA, Ince C, Holleman F, Diamant M, Heine RJ, Hoekstra JB, Kastelein JJ, Stroes ES, Vink H. Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes. 2006;55(4):1127-1132. https://doi.org/10.2337/diabetes.55.04.06.db05-1619
Nieuwdorp M, van Haeften TW, Gouverneur MC, Mooij HL, van Lieshout MH, Levi M, Meijers JC, Holleman F, Hoekstra JB, Vink H, Kastelein JJ, Stroes ES. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes. 2006;55(2):480-486. https://doi.org/10.2337/diabetes.55.02.06.db05-1103
Chappell D, Jacob M, Hofmann-Kiefer K, Rehm M, Welsch U, Conzen P, Becker BF. Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion. Cardiovascular Research. 2009;83(2):388-396. https://doi.org/10.1093/cvr/cvp097
Jacob M, Chappell D. Reappraising Starling: the physiology of the microcirculation. Current Opinion in Critical Care. 2013;19(4):282-289. https://doi.org/10.1097/MCC.0b013e3283632d5e
Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. British Journal of Anaesthesia. 2012;108(3):384-394. https://doi.org/10.1093/bja/aer515
Becker BF, Chappell D, Bruegger D, Annecke T, Jacob M. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovascular Research. 2010;87(2):300-310. https://doi.org/10.1093/cvr/cvq137
Moroz VV, Ryzhkov IA. Acute blood loss: regional blood flow and microcirculation (review, part I). Obshchaya reanimatologiya. 2016;12(2):66-89. (In Russ.). https://doi.org/10.15360/1813-9779-2016-2-56-65
Moroz VV, Ryzhkov IA. Acute blood loss: regional blood flow and microcirculation (review, part II). Obshchaya reanimatologiya. 2016;12(5):65-94. (In Russ.). https://doi.org/10.15360/1813-9779-2016-5-65-94
Rehm M, Haller M, Orth V, Kreimeier U, Jacob M, Dressel H, Mayer S, Brechtelsbauer H, Finsterer U. Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy. Anesthesiology. 2001;95(4):849-856. https://doi.org/10.1097/00000542-200110000-00011
Berg S, Engman A, Hesselvik JF, Laurent TC. Crystalloid infusion increases plasma hyaluronan. Critical Care Medicine. 1994;22(10):1563-1567. https://doi.org/10.1097/00003246-199422100-00010
Sokologorskij SV. Glycocalyx is the birth of a new clinical paradigm. Anesteziologiya i reanimatologiya. 2018;(4):22-29. (In Russ.). https://doi.org/10.17116/anaesthesiology201804122
Eskens BJ, Zuurbier CJ, van Haare J, Vink H, van Teeffelen JW. Effects of two weeks of metformin treatment on whole-body glycocalyx barrier properties in db/db mice. Cardiovascular Diabetology. 2013;12:175. https://doi.org/10.1186/1475-2840-12-175
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):572-576. https://doi.org/10.1097/SHK.0b013e318157e926
Henry CB, Duling BR. TNF-alpha increases entry of macromolecules into luminal endothelial cell glycocalyx. American Journal of Physiology. Heart and Circulatory Physiology. 2000;279(6):2815-2823. https://doi.org/10.1152/ajpheart.2000.279.6.H2815
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. American Journal of Physiology. Heart and Circulatory Physiology. 2005;289(5):1993-1999. https://doi.org/10.1152/ajpheart.00218.2005
Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, Ko TC, Paredes A. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesthesia and Analgesia. 2011;112(6):1289-1295. https://doi.org/10.1213/ANE.0b013e318210385c
Gouverneur M, Spaan JA, Pannekoek H, Fontijn RD, Vink H. Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. American Journal of Physiology. Heart and Circulatory Physiology. 2006;290(1):458-452. https://doi.org/10.1152/ajpheart.00592.2005
Subramanian SV, Fitzgerald ML, Bernfield M. Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor receptor activation. The Journal of Biological Chemistry. 1997;272(23):14713-14720. https://doi.org/10.1074/jbc.272.23.14713
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Archiv. 2007;454(3):345-359. https://doi.org/10.1007/s00424-007-0212-8
Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014;69(7):777-784. https://doi.org/10.1111/anae.12661
Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116(17):1896-1906. https://doi.org/10.1161/CIRCULATIONAHA.106.684852
Henry CB, Duling BR. Permeation of the luminal capillary glycocalyx is determined by hyaluronan. The American Journal of Physiology. 1999;277(2 Pt 2):508-514. https://doi.org/10.1152/ajpheart.1999.277.2.H508
Constantinescu AA, Vink H, Spaan JA. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23(9):1541-1547. https://doi.org/10.1161/01.ATV.0000085630.24353.3D
Lipowsky HH, Gao L, Lescanic A. Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. American Journal of Physiology. Heart and Circulatory Physiology. 2011;301(6):2235-2245. https://doi.org/10.1152/ajpheart.00803.2011
Becker BF, Jacob M, Leipert S, Salmon AH, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. British Journal of Clinical Pharmacology. 2015;80(3):389-402. https://doi.org/10.1111/bcp.12629
Vink H, Duling BR. Capillary endothelial surface layer selectively reduces plasma solute distribution volume. American Journal of Physiology. Heart and Circulatory Physiology. 2000;278(1):285-289. https://doi.org/10.1152/ajpheart.2000.278.1.H285
Kolářová H, Ambrůzová B, Svihálková Šindlerová L, Klinke A, Kubala L. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators of Inflammation. 2014;2014:694312. https://doi.org/10.1155/2014/694312
Florian JA, Kosky JR, Ainslie K, Pang Z, Dull RO, Tarbell JM. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circulation Research. 2003;93(10):136-142. https://doi.org/10.1161/01.RES.0000101744.47866.D5
Yen W, Cai B, Yang J, Zhang L, Zeng M, Tarbell JM, Fu BM. Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo. PLoS One. 2015;10(1):e0117133. https://doi.org/10.1371/journal.pone.0117133
Pati S, Matijevic N, Doursout MF, Ko T, Cao Y, Deng X, Kozar RA, Hartwell E, Conyers J, Holcomb JB. Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw. The Journal of Trauma. 2010;69(suppl 1):S55-S63. https://doi.org/10.1097/TA.0b013e3181e453d4
Torres LN, Sondeen JL, Ji L, Dubick MA, Torres Filho I. Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats. The Journal of Trauma and Acute Care Surgery. 2013;75(5):759-766. https://doi.org/10.1097/TA.0b013e3182a92514
Potter DR, Baimukanova G, Keating SM, Deng X, Chu JA, Gibb SL, Peng Z, Muench MO, Fomin ME, Spinella PC, Kozar R, Pati S. Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock. The Journal of Trauma and Acute Care Surgery. 2015;78(6 suppl 1):7-17. https://doi.org/10.1097/TA.0000000000000630
Jacob M, Bruegger D, Rehm M, Welsch U, Conzen P, Becker BF. Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability. Anesthesiology. 2006104(6):1223-1231. https://doi.org/10.1097/00000542-200606000-00018
Jacob M, Paul O, Mehringer L, Chappell D, Rehm M, Welsch U, Kaczmarek I, Conzen P, Becker BF. Albumin augmentation improves condition of guinea pig hearts after 4 h of cold ischemia. Transplantation. 2009;87(7):956-965. https://doi.org/10.1097/TP.0b013e31819c83b5
Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, Wang W, Zaske AM, Menge T, Kozar RA. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011;6(8):e23530. https://doi.org/10.1371/journal.pone.0023530
Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. The Journal of Trauma. 2007;63(4):805-813. https://doi.org/10.1097/TA.0b013e3181271ba3
Deng X, Cao Y, Huby MP, Duan C, Baer L, Peng Z, Kozar RA, Doursout MF, Holcomb JB, Wade CE, Ko TC. Adiponectin in fresh frozen plasma contributes to restoration of vascular barrier function after hemorrhagic shock. Shock. 2016;45(1):50-54. https://doi.org/10.1097/SHK.0000000000000458
Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper GJ, Perkins JG, Spinella PC, Williams KL, Park MS. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Annals of Surgery. 2008;248(3):447-458. https://doi.org/10.1097/SLA.0b013e318185a9ad
Pati S, Peng Z, Wataha K, Miyazawa B, Potter DR, Kozar RA. Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock. PLoS One. 2018;13(2):e0192363. https://doi.org/10.1371/journal. pone.0192363
Wu F, Peng Z, Park PW, Kozar RA. Loss of syndecan-1 abrogates the pulmonary protective phenotype induced by plasma after hemorrhagic shock. Shock. 2017;48(3):340-345. https://doi.org/10.1097/SHK.0000000000000832
Gambaro G, Cavazzana AO, Luzi P, Piccoli A, Borsatti A, Crepaldi G, Marchi E, Venturini AP, Baggio B. Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney International. 1992;42(2):285-291. https://doi.org/10.1038/ki.1992.288
Gambaro G, Venturini AP, Noonan DM, Fries W, Re G, Garbisa S, Milanesi C, Pesarini A, Borsatti A, Marchi E, et al. Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy. Kidney International. 1994;46(3):797-806. https://doi.org/10.1038/ki.1994.335
Dedov I, Shestakova M, Vorontzov A, Palazzini E. A randomized, controlled study of sulodexide therapy for the treatment of diabetic nephropathy. Nephrology, Dialysis, Transplantation. 1997;12(11):2295-2300. https://doi.org/10.1093/ndt/12.11.2295
Tamsma JT, van der Woude FJ, Lemkes HH. Effect of sulphated glycosaminoglycans on albuminuria in patients with overt diabetic nephropathy. Nephrology, Dialysis, Transplantation. 1996;11(1):182-185.
Solini A, Vergnani L, Ricci F, Crepaldi G. Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care. 1997;20(5):819-823. https://doi.org/10.2337/diacare.20.5.819
Broekhuizen LN, Lemkes BA, Mooij HL, Meuwese MC, Verberne H, Holleman F, Schlingemann RO, Nieuwdorp M, Stroes ES, Vink H. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010;53(12):2646-2655. https://doi.org/10.1007/s00125-010-1910-x
Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M. One year course of oral sulodexide in the management of diabetic nephropathy. Journal of Nephrology. 2005;18(5):568-574.
Li T, Liu X, Zhao Z, Ni L, Liu C. Liu Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury rat carotid artery model. Oncotarget. 2017;8(53):91350-91361. https://doi.org/10.18632/oncotarget.20518
Rehm M, Zahler S, Lötsch M, Welsch U, Conzen P, Jacob M, Becker BF. Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed. Anesthesiology. 2004;100(5):1211-1223. https://doi.org/10.1097/00000542-200405000-00025
Statkevicius S, Bonnevier J, Fisher J, Bark BP, Larsson E, Öberg CM, Kannisto P, Tingstedt B, Bentzer P. Albumin infusion rate and plasma volume expansion: a randomized clinical trial in postoperative patients after major surgery. Critical Care. 2019;23(1):191. https://doi.org/10.1186/s1305 4-019-2477-7
Milford EM, Reade MC. Resuscitation fluid choices to preserve the endothelial glycocalyx. Critical Care. 2019;23(1):77. https://doi.org/10.1186/s1305 4-019-2369-x.
Chappell D, Jacob M, Hofmann-Kiefer K, Bruegger D, Rehm M, Conzen P, Welsch U, Becker BF. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007;107(5):776-784. https://doi.org/10.1097/01.anes.0000286984.39328.96
Annane D. Glucocorticoids in the treatment of severe sepsis and septic shock. Current Opinion in Critical Care. 2005;11(5):449-453. https://doi.org/10.1097/01.ccx.0000176691.95562.43
Mukaida N, Zachariae CC, Gusella GL, Matsushima K. Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. Journal of Immunology. 1991;146(4):1212-1215.
Hafezi-Moghadam A, Simoncini T, Yang Z, Limbourg FP, Plumier JC, Rebsamen MC, Hsieh CM, Chui DS, Thomas KL, Prorock AJ, Laubach VE, Moskowitz MA, French BA, Ley K, Liao JK. Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nature Medicine. 2002;8(5):473-479. https://doi.org/10.1038/nm0502-473
Yang S, Zhang L. Glucocorticoids and vascular reactivity. Current Vascular Pharmacology. 2004;2(1):1-12. https://doi.org/10.2174/1570161043476483
Atkinson JP, Waldmann TA, Stein SF, Gelfand JA, Macdonald WJ, Heck LW, Cohen EL, Kaplan AP, Frank MM. Systemic capillary leak syndrome and monoclonal igg gammopathy. Medicine. 1977;56(3):225-239. https://doi.org/10.1097/00005792-197705000-00004
Pesonen E, Keski-Nisula J, Andersson S, Palo R, Salminen J, Suominen PK. High-dose methylprednisolone and endothelial glycocalyx inpaediatric heart surgery. Acta Anaesthesiologica Scandinavica. 2016;60(10):1386-1394. https://doi.org/10.1111/aas.12785
Afshari A, Wetterslev J, Brok J, Moller A. Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ. 2007;335(7632):1248-1251. https://doi.org/10.1136/bmj.39398.682500.25
Opal SM, Kessler CM, Roemisch J, Knaub S. Antithrombin, heparin, and heparan sulfate. Critical Care Medicine. 2002;30(5 suppl):325-331. https://doi.org/10.1097/00003246-200205001-00024
Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Research in Cardiology. 2009;104(1):78-89. https://doi.org/10.1007/s00395-008-0749-5
Li X, Sun S, Wu G, Che X, Zhang J. Effect of Hydroxyethyl Starch Loading on Glycocalyx Shedding and Cerebral Metabolism During Surgery. The Journal of Surgical Research. 2020;246:274-283. https://doi.org/10.1016/j.jss.2019.09.030
Bruegger D, Rehm M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Conzen P, Becker BF. Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts. Critical Care. 2008;12(3):73. https://doi.org/10.1186/cc6913
Annecke T, Chappell D, Chen C, Jacob M, Welsch U, Sommerhoff CP, Rehm M, Conzen PF, Becker BF. Sevoflurane preserves the endothelial glycocalyx against ischaemia-reperfusion injury. British Journal of Anaesthesia. 2010;104(4):414-421. https://doi.org/10.1093/bja/aeq019
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):483-491. https://doi.org/10.1097/ALN.0b013e3182289988
Flameng W, Borgers M, Van der Vusse GJ, Demeyere R, Vandermeersch E, Thoné F, Suy R. Cardioprotective effects of lidoflazine in extensive aorta-coronary bypass grafting. The Journal of Thoracic and Cardiovascular Surgery. 1983;85(5):758-768.
Golubev AM, Kuzovlev AN, Sundukov DV, Golubev MA. Morphological characteristics of the lungs during inhalation of lipopolysaccharide and perfluorane. Obshchaya reanimatologiya. 2015;11(1):6-13. (In Russ.). https://doi.org/10.15360/1813-9779-2015-1-6-13
Ushakova ND, Shevchenko AN, Chetverikov MV, Zlatnik EYu, Zykova TA. Results of selective endotoxin adsorption in sepsis in cancer patients. Obshchaya reanimatologiya. 2014;10(6):32-38. (In Russ.). https://doi.org/10.15360/1813-9779-2014-6-32-38
Bazhina ES, Nikulin AV, Horoshilov SE. Extracorporeal methods of treatment of abdominal sepsis. Obshchaya reanimatologiya. 2015;11(5):45-66. (In Russ.). https://doi.org/10.15360/1813-9779-2015-5-45-66

Close metadata