Functional metabolic characteristics of intact pig livers during prolongedpotential for a extracorporeal, perfusion: Unique biological liver-assist device

Background. The clinical development of liver-support devices based on perf usion of either pig hepatocytes cartridges or whole pig livers has been ham pered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient e xposure to pig zoonotic diseases. Methods. We designed an original system in which an isolated intact pig liv er was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major ph ysiological and functional parameters. The perfusion circuit further includ ed an interface membrane to provide for separation of patient and liver per fusion circulation. Results. Prolonged (6-21 hr) liver perfusion did not produce significant li ver damage as reflected by modest rises in the levels of the serum transami nases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was d ocumented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver clear ed 82% and 79% of peak bilirubin and ammonia concentrations with clearing k inetics identical throughout perfusion. Indocyanine green clearance was ide ntical to that observed in the living donor before explant surgery. Conclusions. In conclusion, the extracorporeal pig liver perfusion apparatu s described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and re cipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.