Increased serum phospholipase A2 activity after non-heart-beating donor liver transplantation and association with ischemia-reperfusion injury.
BACKGROUND
Secretory phospholipase A(2) (sPLA(2)) degrades cell membrane phospholipids and plays an important role in the synthesis of pro-inflammatory lipid mediators (arachidonic acid and cytokines) during inflammatory events such as ischemia-reperfusion injury after liver transplantation (LTx). A role for sPLA(2) in LTx from non-heart-beating donors (NHBD) has never been demonstrated. Furthermore data on the natural sPLA(2) inhibition capacity are scarce.


METHODS
Using our previously validated pig model of NHBD-LTx, we evaluated changes in sPLA(2) enzyme activity in serum early after reperfusion of livers exposed to warm ischemia. Porcine livers were exposed to incremental periods of warm ischemia, procured, and transplanted after 4 h of cold storage. In serum samples, collected prior to and after reperfusion, sPLA(2) enzyme activity, tumor necrosis factor-alpha, and interleukin-6 levels were determined.


RESULTS
After reperfusion, sPLA(2) activity increased and peaked significantly at 60 min in recipients with primary nonfunction (PNF). Tumor necrosis factor-alpha and interleukin-6 peaked later (at 180 min) in these PNF recipients. We observed a strong natural inhibition of sPLA(2) activity in serum at baseline; this inhibition was substantial reduced 1 h after reperfusion in both PNF and non-PNF recipients. In the non-PNF recipients, however, this natural PLA(2) inhibition was restored within 24 h after reperfusion.


CONCLUSIONS
This study suggests that an increased sPLA(2) activity and a reduced inhibition may play an important role in the pathogenesis of ischemia-reperfusion injury of NHBD liver grafts.
Monbaliu
Diethard R L
DR
Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
Dubuisson
Christel N T
CN
Zeegers
Marcel M M
MM
Crabbé
Martine M J
MM
Fevery
Johan M J
JM
Pirenne
Jacques M F
JM
van Pelt
Jos F
JF
D000818:Animals; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000502:physiology; D016031:Liver Transplantation / Q000502:physiology*; D054467:Phospholipases A2 / Q000097:blood / Q000378:metabolism*; D011183:Postoperative Complications / Q000097:blood*; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology*; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D054467:Phospholipases A2