AccScience Publishing / JCTR / Volume 5 / Issue 5 / DOI: 10.18053/jctres.05.202005.004
ORIGINAL ARTICLE

Hemodilution causes glycocalyx shedding without affecting vascular endothelial barrier permeability in rats

Bülent Ergin1,2* Philippe Guerci2,3,4 Zühre Uz2 Martin Westphal5 Yasin Ince2 Matthias P Hilty2 Can Ince1,2
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1 Department of Adult Intensive Care, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
2 Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
3 INSERM U1116, University of Lorraine, VandoeuvreLes-Nancy, France
4 Department of Anesthesiology and Critical Care Medicine, University Hospital of Nancy, France
5 Fresenius Kabi Deutschland GmbH, Bad Homburg, Germany
Received: 7 January 2020 | Revised: 9 March 2020 | Accepted: 14 April 2020 | Published online: 12 May 2020
© 2020 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: The consequences of acute normovolemic hemodilution (ANH) following different types of fluids on the different components of the glycocalyx and on vascular barrier permeability (VBP) remain unknown.

Aim: To investigate whether the microcirculatory disruption and glycocalyx shedding induced by ANH alters VBP and whether this is affected by the composition and volume of the resuscitation fluid.

Methods: Anesthetized Wistar albino rats (n = 24) underwent stepwise ANH at hematocrit levels of 35%, 25%, 20%, and 15% induced by the exchange of blood with 6% balanced hydroxyethyl starch (1:1), balanced crystalloid (1:3), and normal saline (NS) (1:3). Glycocalyx-shed products were measured at each level of hemodilution. VBP was reflected in the decay of fluorescence dyes of different molecular size and their plasma retention ratios. Edema was assessed by measuring organ water content and muscle microcirculation by hand-held videomicroscopy.

Results: NS caused increased degradation of heparan sulfate and hyaluronan compared with the control group (P = 0.003, P = 0.004, respectively). Neither VBP nor tissue edema was affected by the fluid used. The total and perfused vessel densities within the microcirculation of muscle tissue decreased at hematocrit 15% in the balanced crystalloid (P = 0.02) and NS groups only (P < 0.0001, P = 0.0003, respectively) compared with baseline.

Conclusion: Balanced colloid solution preserved the glycocalyx layer better than balanced and unbalanced crystalloid solutions while maintaining the microcirculatory function associated with an improved total intravascular volume. Among the fluids tested, NS caused the most microcirculatory alterations. While ANH caused the degradation of glycocalyx components regardless of fluid, it did not disrupt the vascular barrier as indicated by macromolecular leakage.

Relevance for patients: The results of this study provide insight into the choice of fluid for optimal perioperative fluid management and the consequences of fluid type on the vascular barrier, glycocalyx, and microcirculation.

Keywords
acute normovolemic hemodilution
fluids
glycocalyx
hydroxyethyl starch
microcirculation
vascular barrier permeability
Conflict of interest
Dr Can Ince runs an internet site microcirculationacademy.org which offers services (e.g., training, courses, and analysis) related to clinical microcirculation and, has received honoraria and independent research grants from Fresenius-Kabi, Baxter Health Care, and AM-Pharma; has developed SDF imaging; is listed as an inventor on related patents commercialized by MicroVision Medical under a license from the Academic Medical Centre; and has been a consultant for MicroVision Medical in the past but has not been involved with this company for more than 5 years. The company that developed the CytoCam-IDF imaging system, Braedius Medical, is owned by a relative of Dr Ince. Dr Ince has no financial relationship with Braedius Medical (i.e., never owned shares or received consultancy or speaker fees). Prof. Martin Westphal is chief medical officer of Fresenius kabi. The remaining authors declare no conflicts of interest.
References

[1] Bampoe S, Odor PM, Dushianthan A, Bennett-Guerrero E, Cro S, Gan TJ, et al. Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures. Cochrane Database Syst Rev 2017;9:CD004089.

[2] Qureshi SH, Rizvi SI, Patel NN, Murphy GJ. Meta-analysis of colloids versus crystalloids in critically ill, trauma and surgical patients. Br J Surg 2016;103:14-26.

[3] Grant MC, Resar LM, Frank SM. The Efficacy and Utility of Acute Normovolemic Hemodilution. Anesth Analg 2015;121:1412-4.

[4] Zhou X, Zhang C, Wang Y, Yu L, Yan M. Preoperative Acute Normovolemic Hemodilution for Minimizing Allogeneic Blood Transfusion: A Meta-Analysis. Anesth Analg 2015;121:1443-55.

[5] Chappell D, Bruegger D, Potzel J, Jacob M, Brettner F, Vogeser M, et al. Hypervolemia Increases Release of Atrial Natriuretic Peptide and Shedding of the Endothelial Glycocalyx. Crit Care 2014;18:538.

[6] Makaryus R, Miller TE, Gan TJ. Current Concepts of Fluid Management in Enhanced Recovery Pathways. Br J Anaesth 2018;120:376-83.

[7] Guerci P, Ergin B, Uz Z, Ince Y, Westphal M, Heger M, et al. Glycocalyx Degradation is Independent of Vascular Barrier Permeability Increase in Nontraumatic Hemorrhagic Shock in Rats. Anesth Analg 2019;129:598-607.

[8] Walker AM, Xiao Y, Johnston CR, Rival DE. The Viscous Characterization of Hydroxyethyl Starch (HES) Plasma Volume Expanders in a Non-Newtonian Blood Analog. Biorheology 2013;50:177-90.

[9] Aykut G, Veenstra G, Scorcella C, Ince C, Boerma C. Cytocam-IDF (Incident Dark Field Illumination) Imaging for Bedside Monitoring of the Microcirculation. Intensive Care Med Exp 2015;3:40.

[10] Massey MJ, Shapiro NI. A Guide to Human In Vivo Microcirculatory Flow Image Analysis. Crit Care 2016;20:35.

[11] Cabrales P, Tsai AG. Plasma Viscosity Regulates Systemic and Microvascular Perfusion during Acute Extreme Anemic Conditions. Am J Physiol Heart Circ Physiol 2006;291:H2445-52.

[12] Martini J, Cabrales P, Tsai AG, Intaglietta M. Mechanotransduction and the Homeostatic Significance of Maintaining Blood Viscosity in Hypotension, Hypertension and Haemorrhage. J Intern Med 2006;259:364-72.

[13] Guerci P, Tran N, Menu P, Losser MR, Meistelman C, Longrois D. Impact of Fluid Resuscitation with Hypertonic-hydroxyethyl Starch Versus Lactated Ringer on Hemorheology and Microcirculation in Hemorrhagic Shock. Clin Hemorheol Microcirc 2014;56:301-17.

[14] Weinbaum S, Tarbell JM, Damiano ER. The Structure and Function of the Endothelial Glycocalyx Layer. Annu Rev Biomed Eng 2007;9:121-67.

[15] Curry FE, Adamson RH. Endothelial Glycocalyx: Permeability Barrier and Mechanosensor. Ann Biomed Eng 2012;40:828-39.

[16] Rehm M, Zahler S, Lötsch M, Welsch U, Conzen P, Jacob M, et al. Endothelial Glycocalyx as an Additional Barrier Determining Extravasation of 6% Hydroxyethyl Starch or 5% Albumin Solutions in the Coronary Vascular Bed. Anesthesiology 2004;100:1211-23.

[17] van Golen RF, Reiniers MJ, Vrisekoop N, Zuurbier CJ, Olthof PB, van Rheenen J, et al. The Mechanisms and Physiological Relevance of Glycocalyx Degradation in Hepatic Ischemia/Reperfusion Injury. Antioxid Redox Signal 2014;21:1098-118.

[18] Chignalia AZ, Yetimakman F, Christiaans SC, Unal S, Bayrakci B, Wagener BM, et al. The Glycocalyx and Trauma: A Review. Shock 2016;45:338-48.

[19] Tuma M, Canestrini S, Alwahab Z, Marshall J. Trauma and Endothelial Glycocalyx: The Microcirculation Helmet? Shock 2016;46:352-7.

[20] Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascón GA, et al. The Endothelium in Sepsis. Shock 2016;45:259-70.

[21] Zuurbier CJ, Demirci C, Koeman A, Vink H, Ince C. Shortterm Hyperglycemia Increases Endothelial Glycocalyx Permeability and Acutely Decreases Lineal Density of Capillaries with Flowing Red Blood Cells. J Appl Physiol 2005;99:1471-6.

[22] Ikonomidis I, Marinou M, Vlastos D, Kourea K, Andreadou I, Liarakos N, et al. Effects of Varenicline and Nicotine Replacement Therapy on Arterial Elasticity, Endothelial Glycocalyx and Oxidative Stress during a 3-Month Smoking Cessation Program. Atherosclerosis 2017;262:123-30.

[23] American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice Guidelines for Perioperative Blood Management: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management*. Anesthesiology 2015;122:241-75.

[24] Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA 2016;316:2025-35.

[25] Johannes T, Mik EG, Nohé B, Unertl KE, Ince C. Acute Decrease in Renal Microvascular PO2 during Acute Normovolemic Hemodilution. Am J Physiol Renal Physiol 2007;292:F796-803.

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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing