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Background/aims: Orthotopic liver transplantation (OLTx) from non-heart beating donor (NHBD) often involves hepatic warm ischemia and reperfusion injury which is triggered by the inflammatory cytokines. This study was carried out to investigate whether a newly synthesized cytokine suppressive anti-inflammatory agent, FR167653, attenuates graft injury in OLTx from NHBD., Methodology: Porcine OLTx from NHBD was performed. No-heart beating time was scheduled to be 60 minutes. Animals were divided into two groups: no treatment control (CT) group (n=5), and FR167653 treated (FR) group (n=5), in which FR167653 was administered intravenously before the aortic cross clamp in the donor, and before and after the hepatic allograft reperfusion in the recipient continuously., Results: Four out of five pigs died within 24 hours and one on postoperative day 1 from graft liver failure in the CT group, while two pigs died on day 3, and three survived more than 7 days in the FR group (p<0.05). Microcirculatory disturbance was attenuated, liver injury was lessened, and ATP resynthesis was enhanced in the FR group. Additionally, FR167653 inhibited neutrophils infiltration in the liver tissue, and suppressed release of inflammatory cytokines after OLTx from NHBD., Conclusions: The treatments with FR167653 successfully prevented graft injury after OLTx from NHBD by means of improvement of liver microcirculation, and attenuation of neutrophils activation. The inhibitory effect of FR167653 on the release of inflammatory cytokines played an important role in the liver graft protection.

Background/aims: Prolonged cold ischemia time (CIT) during graft preservation and warm ischemia time (WIT) defined as a rewarming time have been reported to cause postoperative graft dysfunction after orthotopic liver transplantation (OLT). However, a synergistic effect of both CIT and WIT on patients of graft survival has not been confirmed. The aim of this study was to determine whether simultaneously prolonged CIT and WIT was associated with early graft outcome after clinical OLT., Methodology: Between May 1997 and July 1998, 186 consecutive OLT cases were divided into 4 groups as follows: group A, CIT < or =12 hrs and WIT < or =45 min; group B, CIT >12 hrs and WIT < or =45 min; group C, CIT < or =12 hrs and WIT >45 min; and group D, CIT > 12 hrs and WIT >45 min. Liver graft survival within 90 days of OLT and early postoperative graft function were analyzed., Results: The graft loss rates were 5.4% in group A, 9.8% in group B, 11.1% in group C, and 42.9% in group D. The mean highest aspartate aminotransferase (AST) values after OLT in group D (3352.3+/-569.4 U/L) was significantly higher than those in groups A (1411.7+/-169.2 U/L) and B (1931.3+/-362.6 U/L)., Conclusions: The simultaneously prolonged cold and warm ischemia time significantly caused hepatic allograft injury and failure, suggesting some synergistic effects of CIT and WIT on postoperative graft function.