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

Ryuta Nishitai, Iwao Ikai, Hiroaki Terajima, Akiyoshi Kanazawa, Osamu Takeyama, Takehiko Uesugi, Hiroshi Okabe, Nagato Katsura, Takakazu Matsushita, Satoshi Yamanokuchi, Koichi Matsuo, Shinichi Sugimoto, Tomohiro Shiotani, Yoshio Yamaoka

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The aim of this study is to detect and analyze risk factors of direct cross-circulation between porcine liver and non-human primates before a clinical application of extracorporeal liver perfusion (ECLP) as a liver-assist method. Porcine livers were perfused with baboon blood in an ECLP system. Six healthy baboons were directly connected to the ECLP system with continuous prostaglandin E1 administration. Cross-circulation was terminated in the following circumstances: (1) hepatic arterial or portal perfusion pressures elevated to 200 or 60 mm Hg, respectively; (2) massive exudative bleeding from the graft surface; or (3) bile output decreased to less than 5 μL/h/g of liver weight. In case 1, cross-circulation was continued for 10 hours. Severe macroscopic hemolysis occurred, and serum hemoglobin (s-Hb) concentration reached a peak of 47 mg/dL. The baboon died of acute renal failure 2 days later. Histological study of the perfused porcine liver showed marked microthrombi formation. In 3 of the later 5 cases, cross-circulation was discontinued 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 at the end of cross-circulation and decreased to the baseline level within 24 hours. These 5 baboons survived without organ dysfunction or immunologic disturbance. When severe hemolysis is avoided, direct cross-circulation using the ECLP system can be achieved without serious complications in nonhuman primates.

Original languageEnglish
Pages (from-to)615-622
Number of pages8
JournalLiver Transplantation
Volume7
Issue number7
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

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