Microcirculatory failure after rat liver transplantation is related to Kupffer cell-derived oxidant stress but not involved in early graft dysfunction.
BACKGROUND
Microcirculatory failure, activation of Kupffer cells (KC), and the formation of reactive oxygen species (ROS) are considered pivotal mechanisms of reperfusion injury after orthotopic liver transplantation. However, the sequence of these events and their impact on early graft function remain controversial. We therefore investigated whether KC induce microcirculatory disturbances through ROS release and whether microcirculatory failure contributes to early graft function after liver transplantation.


METHODS
Donor livers of Lewis rats were pretreated either with saline or with gadolinium chloride (GdCl3), an inhibitor of KC function (n=8 each). Syngeneic OLT was performed after 24 hr of hypothermic preservation in University of Wisconsin solution.


RESULTS
Intravital microscopy revealed significantly higher sinusoidal perfusion rates in GdCl3-treated allografts (92+/-1.1% vs. 75.7+/-0.8%; P<0.001) compared with untreated controls; permanent leukocyte sticking in sinusoids (23.5+/-2.1 vs. 62.6+/-3.3 cells/lobule, P<0.001) and in postsinusoidal venules (153.1+/-10.4 vs. 446.6+/-46.4 cells/mm(2), P<0.001) were markedly attenuated in GdCl3-treated allografts. Improvement of microcirculatory parameters in GdCl3-treated livers was correlated with a significant reduction of plasma glutathione disulfide formation by KC-derived ROS (0.96+/-0.1 microM vs. 1.79+/-0.5 microM; P<0.01). Despite these beneficial effects, GdCl3-pretreatment failed to improve postischemic alanine aminotransferase release and bile flow.


CONCLUSIONS
Microcirculatory failure after liver transplantation is related to KC-derived oxidant stress but not involved in early graft dysfunction.
Schauer
R J
RJ
Department of Surgery, Klinikum Grosshadern, University of Munich, Germany. schauer@gch.med.uni-muenchen.de
Bilzer
M
M
Kalmuk
S
S
Gerbes
A L
AL
Leiderer
R
R
Schildberg
F W
FW
Messmer
K
K
D000818:Animals; D005682:Gadolinium / Q000494:pharmacology; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology*; D014184:Transplantation, Homologous
D005682:Gadolinium; D005978:Glutathione; C038958:gadolinium chloride; D019803:Glutathione Disulfide