Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury.

Abstract

The objective of this work was to test the hypothesis that Intraluminal serine proteases are involved in trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury. Male Sprague-Dawley rats were administrated the serine protease inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, Nafamostat) either intraluminally into the gut or intravenously after a laparotomy (trauma) and then subjected to 90 min of hemorrhagic shock (T/HS) or sham shock (T/SS). Intestinal and lung injury was assessed at 3 h after resuscitation with Ringer's lactate solution. In a second set of experiments, mesenteric lymph was collected from the groups of rats subjected to T/HS or T/SS and its ability to activate normal neutrophils was tested. Lung permeability, pulmonary myeloperoxidase levels, and the bronchoalveolar lavage fluid protein to plasma protein ratio were increased after T/HS but were significantly decreased in the T/HS rats receiving intraluminal (P < 0.05), but not intravenous, nafamostat. Likewise, T/HS-induced intestinal villus injury was less in the nafamostat-treated shock rats (P < 0.05). Last, the ability of T/HS mesenteric lymph to increase PMN CD11b expression or prime neutrophils for an augmented respiratory burst was significantly reduced by the intraluminal administration of nafamostat. Because intraluminal nafamostat reduced T/HS-induced gut and lung injury as well as the neutrophil activating ability of intestinal T/HS lymph, the presence of serine proteases in the ischemic gut may play an important role in T/HS-induced gut and hence lung injury.

• Authors: Edwin A Deitch, Han Ping Shi, Qi Lu, Eleonora Feketeova, Da Zhong Xu
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 19 Issue 5 Pg. 452-6 (May 2003) ISSN: 1073-2322 [Print] United States
• PMID: 12744489 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Benzamidines
• Cell Adhesion Molecules
• Guanidines
• Serine Proteinase Inhibitors
• Serine Endopeptidases
• nafamostat

Topics

• Animals
• Benzamidines
• Cell Adhesion Molecules (drug effects, metabolism)
• Disease Models, Animal
• Guanidines (toxicity)
• Ileum (injuries, pathology)
• Intestinal Mucosa (drug effects, injuries, pathology)
• Lung (drug effects, pathology)
• Lung Injury
• Male
• Neutrophils (physiology)
• Permeability
• Rats
• Rats, Sprague-Dawley
• Regression Analysis
• Respiratory Burst (drug effects, physiology)
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (toxicity)
• Shock, Hemorrhagic (enzymology, etiology, physiopathology)