Plasma activation during splanchnic arterial occlusion shock.
During circulatory shock, activating factors for cells in the microcirculation can be detected in plasma. But the source of such activators has remained uncertain. We have demonstrated recently that homogenates derived from the pancreas but not other peritoneal organs activate naive leukocytes. Production of such activating factors can be blocked by a serine protease inhibitor. Thus, factors generated by pancreatic proteases may possibly produce cellular activation in vivo. Rats were subjected to 90 min of superior mesenteric and celiac artery occlusion followed by reperfusion (SAO shock). In addition, rats were subjected to SAO shock for 120 min, after a 60-min pretreatment prior to occlusion with either saline or the serine protease inhibitor Futhan (nafamostat mesilate, 3.3 mg/kg b.w.). A sham SAO protocol was carried out as a control. Cellular activation was tested by neutrophil pseudopod formation and NBT reduction. Plasma from SAO-shocked animals but not sham shock rats exhibited a significant increase (P < 0.001) in the activation of naive leukocytes. Futhan-treated animals subjected to SAO shock exhibited a significantly higher post-reperfusion blood pressure than non-treated animals (P < 0.005 for all time points greater than 120 minutes), as well as significantly greater survival (P < 0.001). Neutrophil pseudopod formation and plasma peroxide production, an additional index of cellular activation, were significantly lower in Futhan-treated SAO shock plasma (P < 0.05) than levels in non-treated SAO shock animals. These results demonstrate that activating factors for leukocyte are released in SAO shock and can be mitigated by pretreatment with the serine protease inhibitor Futhan. Proteolytically derived plasma factors released during SAO shock may contribute to leukocyte activation and ensuing organ dysfunction.
Kistler
E B
EB
Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412, USA.
Lefer
A M
AM
Hugli
T E
TE
Schmid-Schönbein
G W
GW
D000208:Acute Disease; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001550:Benzamidines; D001685:Biological Factors / Q000097:blood*; D002415:Cats; D002445:Celiac Artery / Q000473:pathology*; D003250:Constriction; D006146:Guanidines / Q000494:pharmacology; D007511:Ischemia / Q000097:blood* / Q000150:complications; D008638:Mesenteric Arteries / Q000473:pathology*; D009201:Myocardial Depressant Factor / Q000097:blood*; D009504:Neutrophils / Q000502:physiology*; D010179:Pancreas / Q000098:blood supply*; D010182:Pancreatic Diseases / Q000097:blood* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood* / Q000209:etiology; D016897:Respiratory Burst; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012769:Shock / Q000097:blood*; D013152:Splanchnic Circulation
D001550:Benzamidines; D001685:Biological Factors; D006146:Guanidines; D009201:Myocardial Depressant Factor; D015842:Serine Proteinase Inhibitors; C032855:nafamostat