Protective effects of urinary trypsin inhibitor (UTI) on hepatic microvasculature in hypotensive brain-dead rats.
OBJECTIVE
We examined the protective effects of a protease inhibitor, urinary trypsin inhibitor (UTI), on livers of brain dead rats associated with systemic hemodynamic instability.


METHODS
Brain death was induced by inflating a balloon catheter placed in the epidural space in rats followed by intravenous administration of UTI for 6 h. The hemodynamic, functional and morphological changes in the liver were examined.


RESULTS
The induction of brain death resulted in a significant decrease in both mean arterial pressure (MAP) and hepatic tissue flow (HTF), and an increase in serum AST and cytokines such as tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC). An increase in the number of sequestered neutrophils and enhanced expressions of intercellular adhesion molecules (ICAM)-1 and CINC were also noted in the liver. The treatment with UTI significantly restored HTF to basal level without affecting MAP, and decreased the number of sequestered neutrophils in the hepatic sinusoids, suppressed the expression of ICAM-1 and CINC in the sinusoids, inhibited the production of serum TNF-alpha and CINC, and inactivated Kupffer cells.


CONCLUSIONS
Intravenous administration of UTI is likely to ease unfavorable effects on the hepatic microvasculature evoked by brain death.
Itabashi
K
K
Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan. itako@kitasato-u.ac.jp
Ito
Y
Y
Takahashi
T
T
Ishii
K
K
Sato
K
K
Kakita
A
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D001794:Blood Pressure; D001926:Brain Death; D018925:Chemokines / Q000097:blood; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000097:blood; D006023:Glycoproteins / Q000494:pharmacology*; D006339:Heart Rate; D007022:Hypotension / Q000188:drug therapy*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007728:Kupffer Cells / Q000648:ultrastructure; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects*; D016031:Liver Transplantation; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014019:Tissue Donors; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C028665:urinastatin