Pathogenesis of hemorrhage-induced bacteria/endotoxin translocation in rats : effects of recombinant bactericidal/permeability-increasing protein

• Published in: Annals of surgery 1995-04, Vol.221 (4), p.398-405
• Main Authors: YONG-MING YAO, SOCHEYL BAHRAMI, LEICHFRIED, G, REDL, H, SCHLAG, G
• Format: Article
• Language: English
• Subjects: Animals; Antimicrobial Cationic Peptides; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Blood Proteins - therapeutic use; Cell Movement; Endotoxins - pharmacokinetics; Escherichia coli - physiology; Human bacterial diseases; Infectious diseases; Male; Medical sciences; Membrane Proteins; Peptide Fragments - pharmacology; Permeability; Rats; Rats, Sprague-Dawley; Recombinant Proteins - therapeutic use; Shock, Hemorrhagic - metabolism; Shock, Hemorrhagic - microbiology; Shock, Hemorrhagic - therapy; Toxemia - metabolism; Toxemia - microbiology; Toxemia - therapy; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0003-4932; 1528-1140
• DOI: 10.1097/00000658-199504000-00011

This study was conducted to determine the role of gut-derived bacteria/endotoxin in the pathogenesis of the multiple-organ damage and mortality, the possible beneficial effect of recombinant bactericidal/permeability-increasing protein (rBPl21), and whether neutralizing endotoxemia by rBPl21 treatment influences tumor necrosis factor (TNF) formation in rats after hemorrhagic shock and resuscitation. Hypovolemic shock might be associated with bacterial or endotoxin translocation as well as systemic sepsis. Similar to bactericidal/permeability-increasing (BPl) protein, rBPl21 has been found to bind endotoxin and inhibit TNF production. A rat model of prolonged hemorrhagic shock (30 to 35 mm Hg for 180 min) followed by adequate resuscitation was employed. Recombinant bactericidal/permeability-increasing protein was administered at 5 mg/kg intravenously. The control group was treated similarly to the BPl group, but received thaumatin as a protein-control preparation in the same dose as rBPl21. Immediately after resuscitation (230 min), plasma endotoxin levels in the control group (61.0 +/- 16.3 pg/mL) were almost neutralized by rBPl21 treatment (13.8 +/- 4.8 pg/mL, p < 0.05). Plasma TNF levels were not significantly influenced by rBPl21 treatment. The 48-hour survival rate was 68.8% in the treatment group versus 37.5% in the control group (p = 0.08). Microscopic histopathologic examination revealed relatively minor damage to various organs in the treatment group. These data suggest that hemorrhagic shock may lead to bacterial/endotoxin translocation with concomitant TNF formation, endogenous endotoxemia may play an important role in the pathogenesis of multiple-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 rBPl21 might be a useful therapeutic agent against endogenous bacteria/endotoxin related disorders in severe hemorrhagic shock.