DOES EX VIVO VASCULAR RESISTANCE REFLECT VIABILITY OF NON-HEART-BEATING LIVERS?

Abstract

P115 Aims: Non-heart-beating (NHB) donor livers could decrease mortality on liver transplant (LTx) waiting lists, but their use is limited by a high risk for primary-non-function (PNF) and the absence of methods to measure this risk. For NHB kidneys, vascular resistance (Vasc Res) during ex vivo Machine Perfusion (MP) is a simple and reliable parameter of postTx viability. The purpose of this study was to evaluate ex vivo methods capable of predicting organ viability in vivo. The study was designed to determine whether ex vivo Vasc Res of livers exposed to various periods of Warm Ischemia (WI) correlates with viability postTx. Methods: Porcine livers were recovered after 0’, 45’, and 90’ WI (5 in each group). These WI times were selected based upon prior in vivo LTx validation-experiments correlating 0’WI with normal viability and no PNF, 45’WI with altered viability and high PNF, and 90’WI with complete loss of viability, universal PNF and recipient death. Livers were flushed by gravity via the Portal Vein (PV) and the Hepatic Artery (HA) with 10L 4°C Histidine-Thryptophane-Ketoglutarate (HTK), and cold stored for 3 hrs. Thereafter, livers were perfused with 4°C modified-Belzer solution, using a specifically designed liver MP prototype (Organ Recovery Systems) including an unlimited flow - pressure controlled (30mmHG) and a flow limited (600ml/min) pressure controlled (7mmHg) system for HA and PV, respectively. Vasc Res were calculated in vivo after WI during liver flush-out and ex vivo continuously thereafter during 24 hrs of MP. Markers of hepatocyte damage (AST/LDH) were analysed in the liver effluent during flush-out and in the MP perfusate. Results: During flush-out, PV Vasc Res was lower than HA Vasc Res in all WI groups (p<0.0001). PV Vasc Res after 90’ WI was higher than after 0’ and 45’WI (p=0.003). A similar trend was seen for HA Vasc Res (higherVasc Res with longer WI) but this did not reach significance (p=0.24). During MP, PV Vasc Res was low from the start (0-0.05 mmHg.min/ml) and remained fairly constant during the 24 hr observation period whereas HA Vasc Res was higher at the start but gradually diminished to reach a more constant value after 4-to-6 hours (0.25 – 0.35 mmHg.min/ml). This evolution was similar in all WI groups and no correlation was observed between HA/PV Vasc Res and WI. AST and LDH in the liver effluent at flush-out and in the MP perfusate correlated with WI (p=0.001). Conclusions: Contrary to the kidney, Vasc Res during ex vivo MP of NHB livers does not correlate with the extent of WI damage and does not predict organ viability/function after Tx in the model studied. Whether modifying the experimental design could unmask this correlation or whether this absence of correlation is inherent in the unique vascular physiology of the liver (double vascular circuit/low resistance sinusoidal network) is under evaluation. Other ex vivo parameters, among them enzyme release, correlate with WI damage and viability postTx.