Elsevier

Transplantation Proceedings

Volume 40, Issue 7, September 2008, Pages 2152-2155
Transplantation Proceedings

Ischemia-reperfusion injury
Experimental: Liver
Effects of Serine Protease Inhibitor and Prostaglandin I2 on Liver Transplantation From Non–Heart-Beating Rat Donors

https://doi.org/10.1016/j.transproceed.2008.06.010Get rights and content

Abstract

Objectives

We sought to preserve the microcirculation as a keystone in liver transplantation from a non–heart-beating donor (NHBD). The purpose of this study was to investigate the cytoprotective effects of a serine protease inhibitor, nafamostat mesilate, and prostaglandin I2 (PGI2) on livers transplanted from NHBDs.

Methods

Male Wistar rats were used in five groups of nine rats each. In group 1, livers were retrieved from heart-beating donors (HB group); in group 2, livers were retrieved from NHBDs that had experienced agonal apnea (NHB group); in group 3, livers were retrieved in the same manner as in the NHBD group but were pretreated with nafamostat mesilate (NM), 0.2 mg/kg/h, (NM group); in group 4, livers were retrieved in the same manner as in the NHBD group but were pretreated with prostaglandin (PG) I2, 33 ng/kg/h for 30 minutes (PG group); and in group 5, livers were retrieved in the same manner as in the NHBD group but were pretreated with NM plus PG, (NM+PG group). Livers were perfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after 6 hours of cold preservation, after which the perfusate and liver tissue were analyzed in one set of experiments. In another set of experiments, livers retrieved and after 1 hour of cold preservation were transplanted according to the Kamada method.

Results

In the NM+PG group, the values of interleukin-1β, tumor necrosis factor–α, and thromboxane B2 were significantly lower than those in the NHB group. At histologic analysis, sinusoidal endothelial cells were well preserved in the NM+PG group. The number of survivors at 7 days after liver transplantation in the 5 groups were 9, 0, 1, 1, and 3, respectively.

Conclusion

The serine protease inhibitor, NM, and PGI2 supported sinusoidal endothelial cells and preserved microcirculation.

Section snippets

Materials and Methods

Male Wistar rats were divided into five groups: in group 1, livers were retrieved from heart-beating donors (HB group); in group 2, livers were retrieved from NHBDs that had experienced agonal apnea (NHB group); in group 3, livers were retrieved in the same manner as in the NHBD group but were pretreated with prostaglandin (PG) I2, 33 ng/kg/h for 30 minutes (PGI2 group); in group 4, livers were retrieved in the same manner as in the NHBD group but were pretreated with nafamostat mesilate (NM),

Experiment 1

Portal flow volume in the NHB group decreased significantly compared with that in the HB group; it was maintained as the same level in the NM+PG group as in the HB group (Table). In the NHB group, the values for IL-1β, TNF-α, and TBX2 were significantly greater than those in the HB group. In contrast, in the NM+PG group, the values were significantly lower than those in the NHB group. Histologic analysis revealed well preserved sinusoidal endothelial cells in the NM+PG group, as in the HB group

Discussion

Successful liver transplantation from NHBD or HB marginal donors enlarges the donor source. However, the criteria and standard retrieval procedure of the grafts from those donors have not yet been established.4 In previous studies, we reported that inflammatory cytokines such as TNF-α and IL-1β were increased at reperfusion after cold preservation.2 We also described sinusoidal microcirculatory disturbance as the primary cause of ischemia-reperfusion injury in ΔLT. The microcirculatory

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Cited by (0)

Supported by Grants-in–Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan and from the Ministry of Welfare of Japan, and by a grant from Tohoku University Graduate School of Medicine.

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