Effects of exogenous endothelin-1 application on liver perfusion in nativeand transplanted porcine livers

Purpose. This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-l (ET) plasma concentratio ns on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). Methods. A standardized gradual increment in systemic ET plasma concentrati on (0-58 pg/ml) was induced by continuous ET-I infusion into the portal vei n in both groups (A: n = 10, B: n = 10). Control animals received only sali ne (n = 5, each group). Hepatic microcirculation (HMC) was quantified by th ermodiffusion electrodes, hepatic artery how (HAF), and portal venous flow (PVF) by Doppler flowmetry. Results. No changes in ET or perfusion parameters were observed in controls . The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A fr om 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 /- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Basel ine HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml /100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/ - 32 ml/100 g/min. No significant alteration in systemic circulation was no ted at the ET concentrations investigated. Conclusions. Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominan tly by reduction of portal venous flow, while the effect of ET on HAF was l ess pronounced. Characteristics of flow impairment in transplanted and nati ve livers were analogous after short cold ischemic graft storage (6 h). (C) 2000 Academic Press.