Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue during cold storage and reperfusion

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.