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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
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.
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.
- 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.