Recombinant N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) 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 (rBPI21) on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock.


METHODS
Prospective, randomized, blinded, and placebo-controlled experimental study.


METHODS
University research laboratory.


METHODS
Anesthetized Sprague-Dawley rats, weighing 220 to 250 g.


METHODS
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 rBPI21 (10 mg/kg) or placebo either before or after shock period.


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 significantly narrowed sinusoids in all shock groups compared with controls (8.5 +/- 0.3 microm vs. 10.0 +/- 0.4 pm). Leukocyte adhesion was markedly increased to comparable values in both placebo groups (619 cells/mm2 and 644 cells/mm2; sham, 168 cells/mm2). Neutralization of endotoxin by administration of rBPI21 before or after shock resulted in plain reduction of pathologic leukocyte-endothelial interaction (138 cells/mm2 and 85 cells/mm2).


CONCLUSIONS
The results support the hypothesis that endotoxin induces microcirculatory alterations after shock, and further suggest a potentially beneficial role of rBPI21 in the treatment of posttraumatic endotoxin-induced inflammatory reactions.
Bauer
C
C
Department of Anesthesiology and Critical Care Medicine, University of Saarland Medical School, Homburg-Saar, Germany.
Riemer-Paxian
I
I
Larsen
R
R
Marzi
I
I
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007962:Leukocytes / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects*; D008565:Membrane Proteins; D008833:Microcirculation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016037:Single-Blind Method; D013997:Time Factors
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein