Graft injury correlated with portal hemodynamics and intra graft endothelin-1 expression in living donor liver transplantaion in relation to graft size (Abstract)

Abstract

OBJECTIVE: Liver grafts from living donors are probably small-for-size for adult recipients. lnjury after reperfusion is common but the degree and mechanism of injury remains unknown. The aim of this study is to assess the degree of injury after reperfusion in living donor liver transplantation in relation to graft size. PATIENTS AND METHODS: From May 8 to Nov 20, 2000, we performed 16 living donor liver transplantation using right lobe graft. Portal pressure was measured continuously before and after reperfusion. Liver biopsies were taken for endothelin-l (ET-1) mRNA detection using quantitative real time PCR and electron microscope examination. Portal vein blood samples were taken for the measurement of plasma nitric oxide (NO) level. RESULTS: The range of graft weight (GW) / standard liver mass (SLM) was 32.8% to 66%. The recipients were grouped according to GW/SLM: group I (n=4): < 40 %; group 2 (n=8): >= 40% and c 60%; group 3 (n=4): > 60%. Two hospital mortalities occurred in group 1 (p =0.04, group 1 vs group 2 and 3). The portal pressure immediately after reperfusion and 10 minutes after reperfusion in group 1 were significantly higher than that in group 3 (37.5 cmH2O vs 27.5 cmH20, p = 0.028; 28.5 cmH2O vs 21.5 cmH20, p = 0,028). The portal pressure 15 and 20 minutes after reperfusion in group 2 were significantly higher than that in group 3 (26.5 cmH2O vs 22 cmH20, p = 0.03; 25.5 cmH20 vs 21 cmH20, p = 0.017). After reperfusion. the intragraft ET-I mRNA level increased to 210% of the baseline level group I but decreased to 19% of the baseline level in patients of group 2 and 3 (p=O.025). Portal vein plasma NO level decreased more significantly after reperfusion in patients of group 1 as compared to those of group 2 and 3 (- 41.6uM vs - 5.5uM, p=0.04). Under electron microscope examination, there were severe mitochondria1 swelling and irregular large gaps between sinusoidal lining cells in the liver biopsy of group I. CONCLUSION: Patients with GW/SLM < 40% have higher portal pressure at early phase after reperfusion. This is accompanied by intragraft up-regulation of ET-I and ultrastructural alterations. The transiently higher portal pressure after reperfusion with the subsequent ET-I overexpression and NO level reduction (leading to sinusoidal contraction) may contribute to the small-for-size graft injury.