Small-for-size Liver Research Articles

Protective effects of simultaneous splenectomy on small-for-size liver graft injury in rat liver transplantation

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small-for-size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)-1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET-1 mRNA and hepatic protein levels of ET-1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET-1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET-1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET-1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET-1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.

Small-For-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

Introduction: Pulmonary complications occurring after liver transplantation frequently lead to mortality. Transplantation of small-forsize liver grafts increases the risk of graft failure. Accordingly, the aim of this study was to investigate whether acute pulmonary injury occurs after small-for-size liver transplantation. Moreover, we reported that NIM811, an inhibitor of the mitochondrial permeability transition (MPT), prevents dysfunction of small-for-size liver grafts. Here, we investigated whether protection of liver grafts by NIM811 also attenuated acute pulmonary injury after small-for-size liver transplantation. Methods: Livers were reduced to 50% of original size, stored in cold UW solution for 6 h and then implanted into recipients of the same or about twice the donor body weight, resulting in half-size and quarter-size liver grafts, respectively. NIM811 (5 μM) was added to the storage solution. Lungs and livers were harvested at 5, 18 and 38 h after implantation. Results: Hepatic necrosis and alanine aminotransferase release were higher after transplantation of quarter-size than full-size and half-size grafts, indicating more severe liver injury. Liver regeneration increased in half-size grafts but was suppressed in quarter-size grafts. NIM811 blocked liver injury and promoted regeneration of quarter-size grafts, as observed previously. Pulmonary histological alterations were minimal at 5-18 h after liver transplantation. After 38 h, infiltration of neutrophils and monocytes/macrophages to pulmonary alveoli occurred with septal thickening and increased cellularity in quarter-size graft recipients. These changes were mild in lungs of full-size and half-size graft recipients. NIM811 decreased alveolar septal thickening, monocyte/macrophage infiltration and neutrophil infiltration by 52, 44 and 51%, respectively. Infiltrating leukocytes can produce reactive oxygen and nitrogen species, leading to cell death. 4-Hydroxynonenal and 3-nitrotyrosine adducts increased markedly in pulmonary leukocytes, vascular endothelial cells and alveolar epithelial cells in quarter-size graft recipients, indicating oxidative/nitrosative stresses. TUNEL-positive vascular endothelial/alveolar epithelial cells were 12- and 8- fold higher in lungs of quarter-size compared to full-size and half-size graft recipients, indicating apoptosis. NIM811 blunted 4-hydroxynonenal and 3-nitrotyrosine adduct formation and attenuated apoptosis by >80% after quarter-size liver transplantation. After transplantation, hepatic IL-1β and TNFα mRNA were 3.3 and 2.5-fold higher in quarter-size than full-size grafts. Pulmonary ICAM-1 expression was also markedly higher in quarter-size graft recipients. NIM811 decreased hepatic IL-1β and TNFα as well as pulmonary ICAM-1 expression. Conclusion: Together, failing small-for-size grafts produce toxic cytokines, leading to pulmonary inflammation and injury. NIM811 decreased hepatic injury and toxic cytokine formation, thus attenuating acute pulmonary injury after small-for-size liver transplantation (NIDDK).

Computed tomography perfusion study of hemodynamic changes and portal hyperperfusion in a rabbit model of small-for-size liver

Portal hyperperfusion in the small-for-size (SFS) liver can threaten survival of rabbits. Therefore, it is important to understand the hemodynamic changes in the SFS liver. Twenty rabbits were divided into two groups: a control group and a modulation group. The control group underwent an extended hepatectomy. The modulation group underwent the same procedure plus splenectomy to reduce portal blood flow. CT perfusion examinations were performed on all rabbits before and after operation. Perfusion parameter values, especially portal vein perfusion (PVP), were analyzed. PVP in the modulation group was lower than in the control group after operation (P=0.002). In the control group, postoperative PVP increased by 193.7+/-55.1% compared with preoperative PVP. A weak correlation was found between the increased percentage of PVP and resected liver-to-body weight ratio (RLBWR) (r=0.465, P=0.033). In the modulation group, postoperative PVP increased by 101.4+/-32.5%. No correlation was found between the increased percentage of PVP and RLBWR (r=0.167, P=0.644). Correlations were found between PVP and serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin after surgery (P<0.05). We successfully evaluated the characteristics of hemodynamic changes as well as the effects of splenectomy in the SFS liver in rabbits by the CT technique.