HYPOTHERMIC MACHINE PERFUSION OF RAT LIVERS PRESERVES ENDOTHELIAL CELL FUNCTION

Abstract

P26 Aims: The present study was conducted to investigate the effects of starch content of the preservation solution during hypothermic machine perfusion (HMP) on hepatic microcirculation and heptocellular function in an isolated perfused rat liver model. Methods: Livers isolated from male Sprague-Dawley rats (200-250g) were perfused with the University of Wisconsin (UW)-lactobinate solution (HMP group, n=6), modified UW solution (starch omitted) (HMP w/o starch group, n=6) at 0.4 ml/min/gliver or statically stored in the UW solution (SCS group, n=5) at 4°C for 24 hr. Following preservation, livers from HMP, HMP w/o starch, SCS and control group (without preservation, n=7) were perfused with Krebs-Henseleit Buffer solution at 37°C for 30 min. Samples were taken every 10 min during 30 min warm perfusion to assess hepatocellular damage and function (LDH and bile production). Endothelial cell function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively. Results: After 24hrs hypothermic preservation, HMP livers showed significant lower initial LDH level (110.1 ± 9.8 U/L) than HMP w/o starch (271.9± 46.7 U/L) and SCS groups (725.1 ± 138.3 U/L) (P < 0.05). After 30min rewarming, HMP displayed significantly lower LDH level (220.1 ± 55.1 U/L in HMP vs. 1371.3±215.9 U/L in HMP w/o starch, 884 ± 71.9 U/L in SCS, P < 0.05), higher bile production (0.82 ± 0.14 in HMP vs. 0.56 ± 0.05 in HMP w/o starch, 0.32 ± 0.08 in SCS unit: μl/min/g liver dry wt, P < 0.05). Endothelial cell function was also improved as indicated by HA uptake (18.6±2.3% in HMP vs. 8.9±2.4% in HMP w/o starch, 13.9±3.6% in SCS) and shorter transient time for albumin were observed in MID experiments (23 s in HMP vs. 49 s in HMP w/o starch, 43 s in SCS, P < 0.05) after 30 min rewarming. Liver wet and dry ratio and histological findings also confirmed ameliorated edema in the tissue of the HMP liver compared with the HMP w/o starch and SCS livers. Conclusions: These results suggest that the HMP with the UW solution improved endothelial cell function compared with SCS and HMP w/o starch following 24hr preservation resulting in less hepatocellular damage. These results also suggest that oncotic support appears to be an important component in preserving hepatic microcirculation.