PATHOGENESIS OF HEMORRHAGE-INDUCED BACTERIA ENDOTOXIN TRANSLOCATION IN RATS - EFFECTS OF RECOMBINANT BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN/

Objective This study was conducted to determine the role of gut-derive d bacteria/endotoxin in the pathogenesis of the multiple-organ damage and mortality, the possible beneficial effect of recombinant bacterici dal/permeability-increasing protein (rBPi(21)), and whether neutralizi ng endotoxemia by rBPI(21) treatment influences tumor necrosis factor (TNF) formation in rats after hemorrhagic shock and resuscitation. Sum mary Background Data Hypovolemic shock might be associated with bacter ial or endotoxin translocation as well as systemic sepsis. Similar to bactericidal/permeabiliiy-increasing (BPI) protein, rBPI(21) has been found to bind endotoxin and inhibit TNF production. Methods A rat mode l of prolonged hemorrhagic shock (30 to 35 mm Hg for 180 min) followed by adequate resuscitation was employed. Recombinant bactericidal/perm eability-increasing protein was administered at 5 mg/kg intravenously. The control group was treated similarly to the BPI group, but receive d thaumatin as a protein-control preparation in the same dose as rBPI( 21). Results Immediately after resuscitation (230 min), plasma endotox in levels in the control group (61.0+/-16.3 pg/mL) were almost neutral ized by rBPI(21) treatment (13.8+/-4.8 pg/mL, p < 0.05). Plasma TNF le vels were not significantly influenced by rBPI(21) treatment. The 48-h our survival rate was 68.8% in the treatment group versus 37.5% in the control group (p = 0.08). Microscopic histopathologic examination rev ealed relatively minor damage to various organs in the treatment group . Conclusions These data suggest that hemorrhagic shock may lead to ba cterial/endotoxin translocation with concomitant TNF formation, endoge nous endotoxemia may play an important role in the pathogenesis of mul tiple-organ failure after shock and trauma, TNF formation at an early stage might be related mainly to mechanisms other than Kupffer's cells activation via lipopolysaccharide, and rBPI(21) might be a useful the rapeutic agent against endogenous bacteria/endotoxin related disorders in severe hemorrhagic shock.