Biliary secretion of extracorporeal porcine livers with single and dual vessel perfusion.
BACKGROUND: Hepatic support systems that provide detoxification without biliary secretion (i.e., isolated hepatocyte systems) are sufficient to improve encephalopathy and bridge patients to transplantation. However, biliary secretion may be critical when hepatic support attempts to restore function and regeneration of the host liver. The purpose of these studies was to optimize the support liver secretory response to bile acid by either single-vessel (portal vein; PV) or dual-vessel (hepatic artery [HA] + PV) perfusions during extracorporeal porcine liver perfusion. METHODS: Extracorporeal porcine liver perfusion of anesthetized pigs was developed using support porcine livers perfused through the PV (n=4) alone and through the HA + PV (n=4) via a venovenous circuit. Support livers were provoked with taurocholate (TC) to enhance bile aqueous and hydrophobic outputs. RESULTS: After cold preservation and reperfusion, both PV and HA + PV livers had initial 1-hr bile aqueous outputs < 15% of in vivo flow, with cholesterol (C) and phospholipid (PC) outputs <25% of in vivo flow. Bile flow was significantly greater for recovered HA + PV livers (3.0+/-0.01 ml/15 min) than PV livers (1.9+/-0.01 ml/15 min). Despite this, PC output was significantly greater for PV than HA + PV livers. The C/PC ratio of PV livers was twice that of HA + PV livers. TC infusion (48 micromol/kg/15 min) of HA + PV livers demonstrated significantly greater increments in bile flow, PC output, and C output than PV livers. CONCLUSION: In the unstimulated state, porcine support livers with dual-vessel perfusion generated greater aqueous and C outputs despite diminished PC output than in those with single-vessel perfusion. TC stimulation increased bile flow, PC output, and C output in dual-perfused livers more than in PV livers. HA + PV perfusion of support livers is the preferred technique for removing hydrophobic compounds that require PC transport for excretion or exist in the aqueous phase.
Foley, DP; Vittimberga, FJ; Quarfordt, SH; Donohue, SE; Traylor, AN; MacPhee, J; McLaughlin, T; Ricciardi, R; Callery, MP; Meyers, WC
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