Organ blood flow after partial hepatectomy in rats: modification by endotoxin-neutralizing bactericidal/permeability-increasing protein (rBPI23).
OBJECTIVE
Both maintenance of adequate perfusion and regeneration of the remnant liver are important in the recovery of liver function after partial hepatectomy. In previous experiments, we have shown that profound hypotension and liver injury can be attenuated by neutralizing endotoxins. The relative contribution of endotoxemia to changes in liver blood flow and blood flow to other major organs after partial hepatectomy is not known. The aim of this study was to examine the effect of endotoxin neutralization on individual organ blood flows including hepatic artery and splanchnic blood flow after experimental partial hepatectomy and its relation to liver cell proliferation.


METHODS
Male Wistar rats underwent either two-thirds partial hepatectomy or sham operation. Treatment consisted of continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23) or control protein. At 4 h after surgery, organ blood flows were measured using the radiolabeled microsphere technique, and at 24 h, proliferation index in liver tissue was calculated.


RESULTS
After partial hepatectomy, blood flows to virtually all organs were significantly lower as compared to values obtained in sham-operated rats. rBPI23 greatly improved hepatic artery flow (p<0.001) but not portal venous flow. These effects of rBPI23 on liver flow preceded an equally enhanced liver cell proliferation (p<0.01). Endotoxin neutralization led to significantly higher flows to some but not all splanchnic organs. Lung perfusion was significantly improved by rBPI23.


CONCLUSIONS
Neutralization of endogenous endotoxins improves liver blood flow after partial hepatectomy and also periportal and pericentral liver cell proliferation. This proliferation effect may result from an increased hepatic artery flow. Lung, colon, spleen and pancreas flow but not kidney flow was greatly enhanced by rBPI23.
Boermeester
M A
MA
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. boermees@worldonline.nl
Houdijk
A P
AP
Straatsburg
I H
IH
van Noorden
C J
CJ
van Leeuwen
P A
PA
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001794:Blood Pressure; D001798:Blood Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006498:Hepatectomy; D006499:Hepatic Artery / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein