Activation of protein C during reperfusion in clinical liver transplantation.
BACKGROUND
Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation.


METHODS
In 10 patients undergoing liver transplantation, we measured plasma protein C and APC levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts pre-, intra-, and postoperatively. Samples of blood entering and leaving the liver were obtained simultaneously to assess changes across the liver.


RESULTS
Protein C level was low preoperatively (65%, range 39%-141%) and remained low throughout surgery. Compared with the preoperative level (107%, range 78%-161%), APC level increased during liver reperfusion (471%, range 183%-917%, P=0.05). A transhepatic decrease in protein C level (-16%, range -45%-5%, P=0.007), but not in APC level, occurred during initial liver reperfusion. At the same time, neutrophil and monocyte activation took place in the liver.


CONCLUSIONS
Despite protein C deficiency, patients with liver insufficiency are able to maintain normal APC levels. During reperfusion, protein C consumption occurs in the liver without concomitant hepatic release of APC, indicating a shortage of APC in the reperfused liver. The process consuming protein C and APC may be related to the simultaneous ongoing neutrophil and monocyte activation within the liver graft, indicating a regulatory role for APC in inflammation.
Ilmakunnas
Minna
M
Transplantation and Liver Surgery Clinic, Fourth Department of Surgery, University of Helsinki, Finland. minna.ilmakunnas@helsinki.fi
Petäjä
Jari
J
Höckerstedt
Krister
K
Mäkisalo
Heikki
H
Fernandez
Jose A
JA
Griffin
John H
JH
Jansson
Sten-Erik
SE
Repo
Heikki
H
Pesonen
Eero J
EJ
D000328:Adult; D000368:Aged; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D011183:Postoperative Complications / Q000378:metabolism; D011486:Protein C / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism
D039481:CD11b Antigen; D011486:Protein C; D019041:L-Selectin