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Fluids reverse the early lipopolysaccharide-induced albumin leakage in rodent mesenteric venules

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Abstract

Objective

Volume resuscitation is clinically beneficial in patients with sepsis, but few data exist concerning the effects of fluid administration on early events in the inflammatory process. Vascular permeability, leukocyte rolling and leukocyte adhesion in the rodent mesenteric microcirculation were assessed in vivo using intravital microscopy, and the effect of fluid administration on lipopolysaccharide (LPS)-induced changes recorded.

Design

Prospective, repeated measures study.

Setting

University hospital laboratory.

Subjects

Male Wistar rats in six groups.

Interventions

All animals underwent intravital microscopic examination of mesenteric post-capillary venules. LPS or vehicle was applied topically. Animals received either no additional fluids, 0.9% saline (16 ml/kg per h) or 5% human albumin (16 ml/kg per h) commencing 30 min prior to LPS/vehicle administration.

Measurements and main results

Leukocyte rolling, firm adhesion and blood velocity were observed directly. Vascular permeability was assessed using the flux of fluorescently labelled albumin into the interstitium. LPS significantly increased the median (IQR) number of leukocytes rolling and firmly adherent relative to baseline (at 60 min rolling increased from 12.0 (10.3–13.8) to 40.3 (36.0–47.5) cells/min; adhesion increased from 1 (1–2) to 17 (12–26) cells/100 μm; n=5, p<0.01). Transvascular albumin flux was significantly increased 45 min after LPS application (p<0.01), but not after vehicle. Administration of either 0.9% saline (n=5) or 5% human albumin (n=6), significantly attenuated LPS-induced increases in albumin flux (p<0.05), leukocyte rolling (p<0.01) and adhesion (p<0.01). Fluid administration did not appear to alter shear rates.

Conclusions

Pre-emptive volume administration with either saline or albumin prevented early LPS-induced microcirculatory changes by an undefined effect that is unrelated to changes in microvascular flow.

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Acknowledgements

Supported by the British Heart Foundation and a non-directional grant from the Plasma Protein Therapeutics Association (Europe).

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Authors and Affiliations

  1. Unit of Critical Care, National Heart and Lung Institute, Imperial College of Science Technology & Medicine, Dovehouse Street, London, SW3 6LY, UK

    Peter B. Anning, Simon J. Finney, Suveer Singh & Timothy W. Evans

  2. Physiological Flow Studies Unit, Imperial College of Science Technology & Medicine, Dovehouse Street, London, SW3 6LY, UK

    C. Peter Winlove

Authors
  1. Peter B. Anning
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  2. Simon J. Finney
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  3. Suveer Singh
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  4. C. Peter Winlove
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  5. Timothy W. Evans
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Corresponding author

Correspondence to Timothy W. Evans.

Additional information

Drs. Anning and Finney are supported by grants from the British Heart Foundation.

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Anning, P.B., Finney, S.J., Singh, S. et al. Fluids reverse the early lipopolysaccharide-induced albumin leakage in rodent mesenteric venules. Intensive Care Med 30, 1944–1949 (2004). https://doi.org/10.1007/s00134-004-2385-3

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  • DOI: https://doi.org/10.1007/s00134-004-2385-3

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