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 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 E(1) 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 microL/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.
Nishitai
R
R
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. rnishi@kuhp.kyoto-u.ac.jp
Ikai
I
I
Terajima
H
H
Kanazawa
A
A
Takeyama
O
O
Uesugi
T
T
Okabe
H
H
Katsura
N
N
Matsushita
T
T
Yamanokuchi
S
S
Matsuo
K
K
Sugimoto
S
S
Shiotani
T
T
Yamaoka
Y
Y
D000818:Animals; D003427:Cross Circulation; D005112:Extracorporeal Circulation; D005260:Female; D006085:Graft Survival; D006461:Hemolysis; D008102:Liver Circulation; D016031:Liver Transplantation; D010215:Papio; D010477:Perfusion; D012307:Risk Factors; D013552:Swine; D014183:Transplantation, Heterologous