Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors.
BACKGROUND
This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia.


METHODS
Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed.


RESULTS
SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%).


CONCLUSIONS
SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.
Net
Marc
M
Transplant Coordination of the Hospital Clínic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. mnet@clinic.ub.es
Valero
Ricard
R
Almenara
Raul
R
Deulofeu
Ramon
R
López-Boado
Miguel A
MA
Capdevila
Lluis
L
Barros
Pablo
P
Bombí
Josep A
JA
Agustí
Mercè
M
Adalia
Ramon
R
Ruiz
Angel
A
Arce
Yolanda
Y
Manyalich
Martí
M
García-Valdecasas
Juan C
JC
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002245:Carbon Dioxide / Q000097:blood; D006323:Heart Arrest; D006499:Hepatic Artery; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D023421:Models, Animal; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D011169:Portal Vein; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D019820:Xanthine / Q000378:metabolism
D000227:Adenine Nucleotides; D002245:Carbon Dioxide; D019820:Xanthine; D012436:S-Adenosylmethionine; D000241:Adenosine; D010100:Oxygen