Prolonging warm ischemia reduces the cold preservation limits of liver grafts in swine

BACKGROUND: The critical shortage of transplantable organs necessitates utilization of unconventional donors. But the safe time limits of cold preservation of liver grafts subjected to warm ischemia (WI) for up to 30 minutes from non-heart-beating-donors (NHBDs) has not been delineated. In this study, we investigated how the limits of cold ischemia (CI) in University of Wisconsin (UW) solution are changed in liver grafts subjected to WI from 10 to 30 minutes. METHODS: A simple porcine NHBD liver transplantation (LT) model was developed. In donors, livers were subjected to 10, 20 or 30 minutes of WI and subsequent different times of CI in UW solution. Animals were divided into three groups (WI 10 min, WI 20 min, WI 30 min, n=13 in each group) and nine subgroups (from CI 6 h to CI 28 h). One-week survival rates of recipients, hepatic function, liver energy metabolism, grafted liver microcirculation and pathological observations of the liver were compared. RESULTS: In the WI 10 min group, the one-week survival rate of the CI 20 h subgroup was significantly higher than in the other two subgroups (CI 24 h and CI 28 h) (P<0.05). Furthermore, the CI 20 h subgroup had a lower level of alanine aminotransferase (ALT), less pathological damage, a higher concentration of adenosine triphosphate (ATP) and microcirculatory blood flow in the grafted livers at 1 hour after reperfusion than the other two subgroups. The same trends were also found in the other two groups (WI 20 min and WI 30 min) and their subgroups. CONCLUSIONS: The cold preservation limits of the liver grafts shortened from 20 to 12 to 6 hours when WItime was prolonged from 10 to 20 to 30 minutes. Only the liver grafts within these time limits could be safely transplanted.