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Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model

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Abstract

Shedding of the endothelial glycocalyx precedes leukocyte activation and adherence in acute inflammation. Rapid administration of crystalloid or colloid fluids for treating hemorrhagic shock may cause endothelial glycocalyx shedding, thereby increasing inflammation. This study aimed to compare the effect of different fluid treatments in a canine shock model on glycocalyx biomarker, hyaluronan, and inflammatory biomarkers. Greyhound dogs under general anesthesia subject to hemorrhage for 60 min were given 20 mL kg−1 of either fresh whole blood (FWB), hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg−1 of isotonic crystalloid (CRYST) over 20 min (n = 6 per group). Plasma biomarkers hyaluronan, interleukin (IL) 6, 8, 10, tumor necrosis factor-α, monocyte chemoattractant protein-1, keratinocyte chemokine-like, and atrial natriuretic peptide were measured at baseline, end of hemorrhage (Shock), end of fluid administration (T20), and then 40 (T60), 100 (T120), and 160 (T180) minutes later. Biomarker concentrations were compared between groups using the Kruskal-Wallis test or Fisher’s exact test (measurable versus unmeasurable) (significance set at P < 0.05). Hyaluronan concentration peaked early in the CRYST group at T20, compared to HES (P = 0.005) and GELO (P = 0.018), and later in the GELO group at T60, compared to FWB (P < 0.001). The CRYST group had significantly more samples with measurable IL6 at T180 (P = 0.015), compared to GELO, and IL10 at T60, T120, and T180 (all P = 0.015), compared to FWB. There were no significant differences in other biomarker concentrations. In conclusion, rapid large-volume crystalloid administered for hemorrhagic shock was associated with increased hyaluronan and a greater inflammatory response.

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Acknowledgments

The authors would like to thank Claire Neil and Kirsty Townsend for their assistance with laboratory work. We also thank Dr. Claire Sharp for assistance with the experimental model and Assoc Prof Kwok Ming Ho for manuscript revision.

Funding

This work was supported by grants awarded by the Canine Research Foundation and the American College of Veterinary Emergency and Critical Care, and departmental funds from the Centre for Clinical Research in Emergency Medicine.

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Authors and Affiliations

  1. Comparative Health Research Group, School of Veterinary and Life Sciences, Murdoch University, 90 South St, Murdoch, Perth, WA, 6163, Australia

    Lisa Smart, C. J. Boyd, M. A. Claus, G. Hosgood & A. Raisis

  2. Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia

    Lisa Smart & E. Bosio

  3. Emergency Medicine, University of Western Australia, Perth, Australia

    Lisa Smart & E. Bosio

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  1. Lisa Smart
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  2. C. J. Boyd
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  3. M. A. Claus
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Correspondence to Lisa Smart.

Ethics declarations

This study was approved by the Institutional Animal Ethics Committee (R2666/14) and was conducted by specialist anesthesia and critical care veterinarians in accordance with the Australian Code for the Care and Use of Animals for Scientific Purposes.

Additional information

The results of this study were, in part, published in abstract form (Critical Care 2018, 22(Suppl 1):P293) as a part of the International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium (March, 2018).

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Smart, L., Boyd, C.J., Claus, M.A. et al. Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model. Inflammation 41, 1515–1523 (2018). https://doi.org/10.1007/s10753-018-0797-4

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