Skip to main content
Download PDF

Volume 15 Supplement 1

31st International Symposium on Intensive Care and Emergency Medicine

Impact of modulation of the endocannabinoid system on the intestinal microcirculation in experimental sepsis

Critical Care volume 15, Article number: P255 (2011) Cite this article

Introduction

The endocannabinoid system (ECS) is upregulated during sepsis [1]. However, the functional outcomes of modulating endocannabinoid signaling during sepsis are currently unclear. Impairment of the intestinal microcirculation during sepsis may cause a breakdown of gut epithelial barrier function and bacterial translocation into the systemic circulation, increasing the systemic inflammatory response [2]. The aim of the present study was to examine the effects of CB1 and CB2 receptor modulation on the intestinal microcirculation in a model of polybacterial sepsis (colon ascendens stent peritonitis (CASP)) using intravital microscopy (IVM).

Methods

We studied six groups of animals (Lewis rats, n = 10 per group): sham operated controls (SHAM), septic controls (CASP), CASP animals treated with CB1 agonist ACEA (2.5 mg/kg i.v.), CASP animals treated with CB1 antagonist AM281 (2.5 mg/kg i.v.), CASP animals treated with CB2 agonist HU308 (2.5 mg/kg i.v.), and CASP animals treated with CB2 antagonist AM630 (2.5 mg/kg i.v.). All treatments were performed immediately after sepsis induction. IVM of the intestinal microcirculation was performed 16 hours following sepsis induction. Leukocyte adhesion and functional capillary density were measured in a blinded fashion.

Results

Following 16 hours of CASP-induced experimental sepsis, a significant increase of leukocyte adhesion in the intestinal submucosal venules (for example, collecting venules (V1): SHAM 35.7 ± 6.2 n/mm2, CASP 214.4 ± 22.6 n/mm2, P < 0.05) was observed. Capillary perfusion of the muscular and mucosal layers of the intestinal wall was significantly reduced (for example, longitudinalis muscular layer: SHAM 143.5 ± 7.6 cm/cm2, CASP 77.1 ± 7.2 cm/cm2). Treatment of CASP animals with the CB1 receptor agonist ACEA reduced leukocyte adhesion (V1 venules: 107.4 ± 5.1 n/mm2), whereas CB2 receptor stimulation did not affect leukocyte adhesion. However, CB2 receptor inhibition by AM630 reduced leukocyte activation significantly (V1 venules: 60.0 ± 14.1 n/mm2) and restored capillary perfusion (longitudinal muscular layer: 114.1 ± 7.6 cm/cm2).

Conclusions

The data suggest that ECS signaling is involved in the impairment of the intestinal microcirculation during sepsis. Blocking CB2 receptor signaling reduces leukocyte activation and improves capillary perfusion in sepsis in rats. The long-term effect of ECS modulation needs further investigation.

References

  1. Varga K, et al.: FASEB J. 1998, 12: 1035-1044.

    CAS  PubMed  Google Scholar 

  2. Spronk PE, et al.: Crit Care. 2004, 8: 462. 10.1186/cc2894

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dalhousie University, Halifax, Canada

    C Lehmann, R Kuschnereit, I Kiister, J Zhou, S Whynot, O Hung, R Shukla, D Henzler, V Cerny, D Pavlovic & M Kelly

Authors
  1. C Lehmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Kuschnereit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I Kiister
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Whynot
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. O Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D Henzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. V Cerny
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D Pavlovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Lehmann, C., Kuschnereit, R., Kiister, I. et al. Impact of modulation of the endocannabinoid system on the intestinal microcirculation in experimental sepsis. Crit Care 15 (Suppl 1), P255 (2011). https://doi.org/10.1186/cc9675

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/cc9675

Keywords

  • Leukocyte Adhesion
  • Capillary Perfusion
  • Functional Capillary Density
  • Sepsis Induction
  • Intestinal Microcirculation

Critical Care

ISSN: 1364-8535