Influence of extracorporeal porcine liver perfusion on nonhuman primates: Minimizing hemolysis improves subsequent survival

The aim of this study is to detect and analyze risk factors of direct cross -circulation between porcine liver and nonhuman primates before a clinical application of extracorporeal liver perfusion (ECLP) as a liver-assist meth od. Porcine livers were perfused with baboon blood in an ECLP system. Six h ealthy baboons were directly connected to the ECLP system with continuous p rostaglandin E-1 administration. Cross-circulation was terminated in the fo llowing circumstances: (1) hepatic arterial or portal perfusion pressures e levated to 200 or GO mm Hg, respectively; (2) massive exudative bleeding fr om the graft surface; or (3) bile output decreased to less than 5 muL/h/g o f liver weight. In case 1, cross-circulation was continued for 10 hours. Se vere macroscopic hemolysis occurred, and serum hemoglobin (s-Hb) concentrat ion reached a peak of 47 mg/dL. The baboon died of acute renal failure 2 da ys later. Histological study of the perfused porcine liver showed marked mi crothrombi formation. In 3 of the later 5 cases, cross-circulation was disc ontinued when mild macroscopic hemolysis was observed. The duration of the 5 cross-circulations was maximally 6 hours (mean, 4.4 +/- 1.2 [SD] hours). Mean s-Hb concentration in the 5 cases was elevated to 14.8 +/- 5.8 mg/dL a t the end of cross-circulation and decreased to the baseline level within 2 4 hours. These 5 baboons survived without organ dysfunction or immunologic disturbance. When severe hemolysis is avoided, direct cross-circulation usi ng the ECLP system can be achieved without serious complications in nonhuma n primates.