Recombinant N-terminal fragment of bactericidal permeability increasing protein (rBPI(21)) prevents shock-induced microcirculatory alterations in the liver

Objective: To investigate the effects of the recombinant 21-kilodalton N-terminal fragment of recombinant bactericidal and permeability increasing protein (rBPI(21)) on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock. Design: Prospective, randomized, blinded, and placebo-controlled experimental study. Setting: University research laboratory. Subjects: Anesthetized Sprague-Dawley rats, weighing 220 to 250 g. Interventions: Rats were subjected to 60 mins of hemorrhagic shock and subsequent resuscitation to sufficiently restore systemic circulation. The microcirculation of the liver was investigated by intravital fluorescence microscopy 5 hrs after hemorrhagic shock. Four shock groups were compared with a sham control group. Shock groups received either rBPI(21)(10 mg/kg) or placebo either before or after shock period. Measurements and Main Results: No differences were observed in hemodynamic, respiratory, or metabolic parameters between the shock groups, However, the hepatic microcirculation showed severe deterioration 5 hrs after shock, indicated by signifi- cantly narrowed sinusoids in all shock groups compared with controls (8.5 +/- 0.3 mu m vs, 10.0 +/- 0.4 mu m). Leukocyte adhesion was markedly increased to comparable values in both placebo groups (619 cells/mm(2) and 644 cells/mm(2); sham, 168 cells/mm(2)), Neutral ization of endotoxin by administration of rBPI(21) before or after shock resulted in plain reduction of pathologic leukocyte endothelial interaction (138 cells/mm(2) and 85 cells/mm(2)). Conclusion: The results support the hypothesis that endotoxin induces microcirculatory alterations after shock, and further suggest a potentially beneficial role of rBPI(21) in the treatment of posttraumatic endotoxin-induced inflammatory reactions.