Sosef Meindert N, Abrahamse Leo S L, van de Kerkhove Maarten-Paul, Hartman Robin, Chamuleau Rob A F M, van Gulik Thomas M
Department of Surgery, Surgical Laboratory, Academic Medical Center, The University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Transplantation. 2002 Jan 27;73(2):204-9. doi: 10.1097/00007890-200201270-00009.
The anhepatic pig model was used to evaluate a bioartificial liver developed in our institution (AMC-BAL). The bioartificial liver is based on oxygenated plasma perfusion of porcine hepatocytes attached to a polyester matrix.
Pigs (n=15) underwent total hepatectomy with restoration of caval continuity using a polyethylene, three-way prosthesis. In group I, pigs received limited intensive care under continuation of general anesthesia (n=5). Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II and III were connected to the extracorporeal system 24 hr after hepatectomy, for a period of 24 hr. The main outcome parameters were as follows: survival time, liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood ammonia, and total/direct bilirubin.
Survival (mean +/- SD) of the anhepatic pigs was significantly increased in the BAL-treated group (group III: 65+/-15 hr), as compared with the control groups (group I: 46+/-6 hr and group II: 43+/-14 hr). Mean blood ammonia levels during BAL treatment were significantly lower in the BAL-treated group in comparison with both control groups (P=0.02). Total and direct bilirubin levels gradually increased after hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl, respectively, showing no differences between the three groups.
(1) Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes significantly increases survival time, which is associated with a significant decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct bilirubin levels as a result of extrahepatic bilirubin conjugation.
采用无肝猪模型评估我们机构研发的生物人工肝(AMC - BAL)。该生物人工肝基于附着于聚酯基质的猪肝细胞的氧合血浆灌注。
15头猪接受全肝切除术,使用聚乙烯三通假体恢复腔静脉连续性。在第一组中,猪在持续全身麻醉下接受有限的重症监护(n = 5)。第二组猪(n = 5)另外接受不含肝细胞的AMC - BAL的体外血浆灌注(设备对照组)。在第三组(n = 5)中,血浆灌注使用装载自体肝细胞的AMC - BAL。第二组和第三组在肝切除术后24小时连接到体外系统,持续24小时。主要观察指标如下:生存时间、肝酶(天冬氨酸转氨酶、丙氨酸转氨酶)、血氨以及总胆红素/直接胆红素。
与对照组相比,生物人工肝治疗组(第三组:65±15小时)无肝猪的生存率显著提高(第一组:46±6小时,第二组:43±14小时)。与两个对照组相比,生物人工肝治疗组在生物人工肝治疗期间的平均血氨水平显著降低(P = 0.02)。肝切除术后总胆红素和直接胆红素水平逐渐升高,分别达到最大值1.98mg/dl和1.50mg/dl,三组之间无差异。
(1)用含有自体肝细胞的AMC - BAL治疗无肝猪可显著提高生存时间,这与血氨显著降低有关。(2)无肝猪由于肝外胆红素结合而出现直接胆红素水平升高。