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Microcirculatory, leukocyte/endothelium interaction and survival time effects of recombinant C-reactive protein in nonhypotensive endotoxemia in hamsters

Introduction

Microcirculatory, leukocyte/endothelium interaction and 7-day survival time effects of human recombinant C-reactive protein (rCRP) associated or not with volume resuscitation were studied in the hamster window chamber model during resuscitation from nonhypotensive endotoxemia [1, 2].

Methods

Awake hamsters subjected to endotoxemia with intravenous injection of lipopolysaccharide (LPS) (2 mg/kg) were divided, 1 hour after LPS injection, into four groups: LPS (n = 6): no treatment; VR (n = 6): received 40 ml/kg body weight of NaCl 0.9% in 1 hour followed by 20 ml/kg body weight during the remaining 4 hours; rCRP (n = 6): received rCRP infusion in the dose of 24 μg/kg/hour during 5 hours; VR/rCRP (n = 6): received 40 ml/kg body weight of NaCl 0.9% in the first hour followed by 20 ml/kg body weight during the remaining 4 hours, and in the last period it was combined with rCRP infusion in the dose of 24 μg/kg/hour. Groups were compared with Control (n = 6): no LPS. Arteriolar and venular diameters, functional capillary density (FCD), venular leukocyte rolling and adhesion, and 7-day survival time were evaluated.

Results

LPS reduced FCD so it was maintained lower than Control and baseline even after 24 hours (13 ± 11 and 100 ± 7% from baseline in LPS and Control, respectively). Volume resuscitation and rCRP restored FCD to baseline levels but it was lower than Control after 24 hours (36 ± 25 and 32 ± 20% from baseline in VR and rCRP, respectively). VR/rCRP restored FCD and it was not different from Control (72 ± 26% from baseline in rCRP). Arteriolar and venular diameters were not different among groups. LPS increased the number of sticking leukocytes to the venular wall (41.2 ± 13 and 1.1 ± 1 leucocytes/mm2 in LPS and Control, respectively). rCRP and VR/rCRP significantly reduced venular leukocyte adhesion (12.6 ± 7.1 and 11.8 ± 9.5 leucocytes/mm2 in rCRP and VR/rCRP, respectively). There was no difference in rolling leukocytes among groups. The survival curve was not significantly different in rCRP, VR and VR/rCRP from Control.

Conclusion

rCRP associated or not with volume resuscitation improved tissue perfusion, reduced the number of sticking leukocytes and increased the survival time during endotoxemia in the hamster model.

References

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    Joyce DE, et al.: Leukocyte and endothelial cell interactions in sepsis: relevance of the protein C pathway. Crit Care Med 2004,32(5 Suppl):S280-S286. 10.1097/01.CCM.0000128037.72072.22

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    Iba T, et al.: Activated protein C improves the visceral microcirculation by attenuating the leukocyte–endothelial interaction in a rat lipopolysaccharide model. Crit Care Med 2005, 33: 368-372. 10.1097/01.CCM.0000153415.04995.88

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Silva, M., Santos, A., Furtado, E. et al. Microcirculatory, leukocyte/endothelium interaction and survival time effects of recombinant C-reactive protein in nonhypotensive endotoxemia in hamsters. Crit Care 13, P243 (2009). https://doi.org/10.1186/cc7407

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Keywords

  • Survival Time
  • Tissue Perfusion
  • Leukocyte Adhesion
  • Volume Resuscitation
  • Leukocyte Rolling