Complement inhibition by soluble complement receptor type 1 improves microcirculation after rat liver transplantation.
BACKGROUND
Recent observations provide evidence that complement is involved in the pathophysiology of ischemia/reperfusion injury. In this study, we assessed the impact of complement inhibition on hepatic microcirculation and graft function using a rat model of liver transplantation.


METHODS
Arterialized orthotopic liver transplantation was performed in Lewis rats after cold preservation (University of Wisconsin solution, 4 degrees C, 24 h). Eight animals received the physiological complement regulator soluble complement receptor type 1 (sCR1) intravenously 1 min before reperfusion. Controls received Ringer's solution (n=8). Microvascular perfusion, leukocyte adhesion, and Kupffer cell phagocytic activity were studied 30-100 min after reperfusion by in vivo microscopy.


RESULTS
Microvascular perfusion in hepatic sinusoids was improved in the sCR1 group (87+/-0.7% vs. 50+/-1%; P < 0.001). The number of adherent leukocytes was reduced in sinusoids (68.3+/-4.7 vs. 334.1+/-15.8 [adherent leukocytes per mm < or = liver surface]; P < 0.001) and in postsinusoidal venules after sCR1 treatment (306.6+/-21.8 vs. 931.6+/-55.9 [adherent leukocytes per mm < or = endothelial surface]; P < 0.001). Kupffer cell phagocytic activity was decreased in the sCR1 group compared to controls. Postischemic bile production reflecting hepatocellular function was increased by almost 200% (P = 0.004) after complement inhibition. Plasmatic liver enzyme activity was decreased significantly upon sCR1 treatment, indicating reduced parenchymal cell injury.


CONCLUSIONS
Our results provide further evidence that the complement system plays a decisive role in hepatic ischemia/reperfusion injury. We conclude that complement inhibition by sCR1 represents an effective treatment to prevent reperfusion injury in liver transplantation.
Lehmann
T G
TG
Department of General Surgery, University of Heidelberg, Germany.
Koeppel
T A
TA
Kirschfink
M
M
Gebhard
M M
MM
Herfarth
C
C
Otto
G
G
Post
S
S
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D003167:Complement Activation / Q000187:drug effects; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology; D007511:Ischemia / Q000188:drug therapy*; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects*; D016031:Liver Transplantation; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010586:Phagocytes / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D011951:Receptors, Complement / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy*
D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; C082885:soluble complement inhibitor 1