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Related Experiment Videos

Plasma activation during splanchnic arterial occlusion shock.

E B Kistler1, A M Lefer, T E Hugli

  • 1Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412, USA.

Shock (Augusta, Ga.)
|July 26, 2000
PubMed
Summary

During circulatory shock, pancreatic proteases release leukocyte-activating factors. Pretreatment with the serine protease inhibitor Futhan significantly improves survival and reduces cellular activation in a rat model of shock.

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Area of Science:

  • Biochemistry
  • Physiology
  • Immunology

Background:

  • Circulatory shock involves plasma-derived activators of microcirculation cells.
  • The origin of these activators, particularly in relation to pancreatic proteases, remained unclear.
  • Previous work indicated pancreatic homogenates activate leukocytes, a process inhibited by serine protease inhibitors.

Purpose of the Study:

  • To investigate the role of pancreatic proteases in generating leukocyte-activating factors during shock.
  • To evaluate the therapeutic potential of a serine protease inhibitor, Futhan, in a rat model of superior mesenteric and celiac artery occlusion (SAO) shock.

Main Methods:

  • Rats underwent SAO shock (90-120 min occlusion/reperfusion).
  • Pretreatment with saline or Futhan (nafamostat mesilate) was administered prior to SAO shock.

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  • Cellular activation assessed via neutrophil pseudopod formation and NBT reduction.
  • Plasma activation of naive leukocytes was measured.
  • Main Results:

    • SAO shock plasma significantly activated naive leukocytes compared to sham shock.
    • Futhan pretreatment significantly improved post-reperfusion blood pressure and survival rates.
    • Futhan treatment significantly reduced neutrophil pseudopod formation and plasma peroxide production.

    Conclusions:

    • Leukocyte-activating factors are released during SAO shock, potentially originating from pancreatic proteases.
    • Serine protease inhibition with Futhan mitigates leukocyte activation and improves outcomes in SAO shock.
    • Proteolytically derived factors contribute to leukocyte activation and organ dysfunction in shock.