Bradley A L, Sika M, Wright J K, Chapman W C, Blair K T, Jabbour K, Williams P E, Donovan K L, Van Buren D H, Flakoll P J, Pinson C W
Division of Hepatobiliary Surgery and Liver Transplantation, Veterans Affairs Medical Center, Nashville, Tennessee, USA.
J Surg Res. 1998 Jan;74(1):47-53. doi: 10.1006/jsre.1997.5225.
The liver is one of the principal organs responsible for the uptake and release of amino acids in the body. The ability of the transplanted liver to clear plasma amino acids is associated with a functioning allograft. However, clinical assessment is limited by the inability to access the portal vein postoperatively. Therefore, using a porcine liver transplant model, we examined (1) the plasma levels of amino acids presented to the new hepatic allograft and (2) the capacity of the new allograft to clear these amino acids from the circulation.
Two groups of commercially bred pigs were studied: a control group (n = 8) underwent laparotomy and a transplanted group (n = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass. All pigs had catheters placed in the carotid artery and portal and hepatic veins and ultrasonic transit time flow probes placed around the hepatic artery and portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure liquid chromatography. Hepatic balances of amino acids, using arteriovenous difference techniques coupled with hepatic blood flows, were also analyzed on postoperative day 1.
Neither portal vein blood flow (703 +/- 74 ml/min vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/- 59 ml/min) was significantly different between the control and the transplanted groups, respectively. The transplanted group had significantly increased plasma levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30 +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10 mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84 +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27 mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted group also had significantly decreased plasma levels of isoleucine (122 +/- 12 mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l). These individual amino acid changes were not accompanied by impairment in the net hepatic amino acid balance or the hepatic fractional extraction of amino acids between the two groups.
These results suggest that the circumstances associated with liver transplantation alter the fasting amino acid profile immediately postoperatively. However, liver transplantation does not impair the normal hepatic allograft uptake of most plasma amino acids. Thus, the changes observed in the circulating levels of amino acids may represent alterations in nonhepatic production and/or utilization. Furthermore, altered plasma amino acid profiles following liver transplantation are not necessarily indicative of impaired hepatic allograft amino acid metabolism.
肝脏是体内负责摄取和释放氨基酸的主要器官之一。移植肝脏清除血浆氨基酸的能力与移植器官的功能相关。然而，临床评估受到术后无法进入门静脉的限制。因此，我们使用猪肝移植模型，研究了（1）进入新肝移植器官的血浆氨基酸水平，以及（2）新移植器官从循环中清除这些氨基酸的能力。
研究了两组商业养殖的猪：对照组（n = 8）接受剖腹手术，移植组（n = 6）使用静脉-静脉旁路进行原位肝移植（LT）。所有猪均在颈动脉、门静脉和肝静脉中放置导管，并在肝动脉和门静脉周围放置超声通过时间血流探头。采用高压液相色谱法分析23种氨基酸的血浆谱。术后第1天还采用动静脉差技术结合肝血流量分析氨基酸的肝平衡。
对照组和移植组的门静脉血流量（分别为703±74 ml/min和666±82 ml/min）和肝动脉血流量（分别为322±43 ml/min和209±59 ml/min）均无显著差异。移植组的血浆丙氨酸（135±13 μmol/l对382±72 μmol/l）、羟脯氨酸（30±5 μmol/l对60±9 μmol/l）、蛋氨酸（25±2 μmol/l对55±10 μmol/l）、鸟氨酸（36±5 μmol/l对141±33 μmol/l）、苯丙氨酸（84±5 μmol/l对120±12 μmol/l）、苏氨酸（75±9 μmol/l对159±27 μmol/l）和色氨酸（17±2 μmol/l对31±4 μmol/l）水平显著升高。移植组的血浆异亮氨酸（122±12 μmol/l对85±8 μmol/l）和牛磺酸（71±7 μmol/l对35±7 μmol/l）水平也显著降低。这些单个氨基酸的变化并未伴随两组间肝氨基酸净平衡或肝氨基酸分数提取的损害。
这些结果表明，与肝移植相关的情况在术后立即改变了空腹氨基酸谱。然而，肝移植并未损害大多数血浆氨基酸在正常肝移植器官中的摄取。因此，循环氨基酸水平的变化可能代表非肝脏产生和/或利用的改变。此外，肝移植后血浆氨基酸谱的改变不一定表明肝移植器官氨基酸代谢受损。
