Endothelin-1 and Big-Endothelin Concentrations Are Elevated in Liver Graft Tissue during Cold Storage and Reperfusion

Abstract

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 ± 20; big-ET: 245 ± 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 ± 16; big-ET: 306 ± 144 pg/mg) compared to baseline (ET: 32 ± 13; big-ET: 185 ± 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 ± 26; big-ET: 163 ± 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 ± 3.0 pg/ml), C, (2.8 ± 1.2 pg/ml) and D (2.6 ± 2.0 pg/ml), compared to baseline (1.7 ± 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.

Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver

“…Because a significant improvement of OCR and bile production was observed only after 60 min or later (data not shown), the primary action of hydrogen gas was apparently to induce vascular relaxation. In their study, the tissue ET-1 level significantly decreased at 90 min after reperfusion in surviving animals, whereas it remained at a high value in non-survivors (28). 4).…”

“…Kraus et al reported that the tissue endothelin-1 level was already augmented during cold preservation and after 5 min of reperfusion in a pig liver transplant model. In their study, the tissue ET-1 level significantly decreased at 90 min after reperfusion in surviving animals, whereas it remained at a high value in non-survivors (28). Tissue blood flow was significantly lower than that of survivors from 5 min to 3 h after reperfusion in the warm hepatic I/R model (8).…”