Graft protein C entrapment is associated with reduced phagocyte activation during reperfusion in human liver transplantation.
OBJECTIVE
To explore the potential anti-inflammatory role of protein C pathway in ischemia-reperfusion injury during liver transplantation.


METHODS
Prospective, observational clinical study.


METHODS
Tertiary teaching hospital.


METHODS
Fifty adult patients undergoing liver transplantation for acute liver failure or chronic liver disease.


METHODS
To assess changes occurring across the transplanted liver, samples of blood entering and leaving the graft were obtained simultaneously from portal and hepatic veins. Plasma protein C and activated protein C levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts were measured. Postoperative liver function and outcome of transplantation were recorded.


RESULTS
During reperfusion, protein C became entrapped within the graft (portal vein 49% [20-96%]; graft caval effluent 25% [12-76%], p < .001), without concomitant activated protein C outflow from the graft. Simultaneously, marked neutrophil and monocyte activation occurred within the graft. Enhanced hepatic protein C entrapment was associated with reduced neutrophil and monocyte activation (R = .377, p = .011; R = .389, p = .008, respectively) during reperfusion.


CONCLUSIONS
Protein C entrapment occurs immediately during reperfusion in the graft without concomitant activated protein C release, suggesting a shortage of activated protein C in the reperfused graft. The ongoing inflammatory response during reperfusion may lead to protein C and activated protein C utilization within the graft. Indeed, hepatic protein C entrapment is associated with reduced hepatic phagocyte activation, suggesting a regulatory role for protein C pathway in hepatic reperfusion in human liver transplantation.
Ilmakunnas
Minna
M
Transplantation and Liver Surgery Clinic, Fourth Department of Surgery, Helsinki University Central Hospital, Finland.
Pesonen
Eero J
EJ
Höckerstedt
Krister
K
Mäkisalo
Heikki
H
Fernandez
Jose A
JA
Griffin
John H
JH
Repo
Heikki
H
Siitonen
Sanna
S
Petäjä
Jari
J
D000328:Adult; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism* / Q000502:physiology; D011486:Protein C / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury / Q000097:blood* / Q000378:metabolism
D011486:Protein C