BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs.
METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8), controls 1, 2 and 3 (C₁, C₂, C₃, n=16), and experimental 1, 2 and 3 (E₁, E₂, E₃, n=16). For groups C₁ and E₁, C₂ and E₂, and C₃ and E₃, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 ℃ Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation.
RESULTS: At 1 hour after portal vein reperfusion, the levels of NO in groups E₁, E₂, E₃ and C₁, C₂, C₃ were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E₁, E₂, E₃ were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C₁, C₂, C₃) (P<0.05). The levels of NO in groups C_{2 and C3 were lower than in group C1 (P<0.05), and the level of NO in group C3 was lower than in group C2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E1, E2, E3 were lower than those in the corresponding control groups (C1, C2, C3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C3 than in groups C1 and C2 (P<0.05). Pathological changes in groups E1, E2, E3 were milder than those in the corresponding experimental control groups (C1, C2, C3).
CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.}