RAPID DONOR LIVER NUTRITIONAL ENHANCEMENT IN A LARGE ANIMAL-MODEL
RAPID DONOR LIVER NUTRITIONAL ENHANCEMENT IN A LARGE ANIMAL-MODEL
复制标题
DOI：
10.1016/0270-9139(92)90024-4
复制
发表时间：
1992-11-01
期刊：
影响因子：
13.5
通讯作者：
STRASBERG, SM
中科院分区：
文献类型：
--
作者：
CYWES, R;GREIG, PD;STRASBERG, SM
器官捐献者通常会出现急性低营养血症，这可能会影响保存后的肝功能。来自营养补充大鼠的肝脏在保存后比来自禁食大鼠的肝脏功能更好。我们已经开发出一种方法，在人类供体肝脏手术的时间背景下，使大型动物的肝脏糖原化，并研究了保存过程中糖原储存的命运。通过上级肠系膜静脉向饥饿的麻醉猪输注己糖溶液（葡萄糖、果糖或半乳糖）3小时。输注常规猪胰岛素以维持高血糖高胰岛素血症动脉葡萄糖钳夹在12至16 mmol/L。在输注前和每小时采集肝脏活检标本和血液样本。在3小时时，切除肝脏，在威斯康星州大学溶液中于1 ℃储存24小时，并进行活组织检查。然后将其置于20 ℃下1小时以模拟移植的再植入阶段。测量糖原和核苷酸水平，并在威斯康星州大学溶液中对结果进行淀粉校正。20%葡萄糖输注产生快速肝糖原化而无副作用。更大的糖化获得20%的果糖，但在乳酸酸中毒和pH值下降的成本。15%的葡萄糖和5%的果糖的组合产生中间糖化没有显着的副作用。半乳糖（20%）的效率低于单独的葡萄糖。丙氨酸和谷氨酰胺（20 mmol/L）的添加没有显着改善糖化。在1 ℃时确实发生糖原代谢。糖原含量在冷保存期间每小时下降0.15% +/- 0.05%肝干重，在缺血复温期间每小时下降5.49% +/- 2.15%。复温期间糖原消耗的速率取决于复温期开始时可用的糖原量。磷酸化核苷酸水平在糖原化肝脏中维持在显著较高的水平。高碘酸-希夫染色显示在1区最大和3区最小的明显的糖原化梯度。在大型动物模型中，快速肝糖原化是可能的，并且在维持腺嘌呤核苷酸水平方面是有益的。
Organ donors are typically subject to acute hyponutrition that might affect postpreservation liver function. Livers from nutritionally supplemented rats function better after preservation than livers from fasted rats. We have developed a method to glycogenate the liver of large animals in the temporal context of a human donor liver operation and have studied the fate of glycogen stores during preservation. Starved anesthetized pigs were infused with a hexose solution (glucose, fructose or galactose) by way of the superior mesenteric vein for 3 hr. Regular porcine insulin was infused to maintain a hyperglycemic hyperinsulinemic arterial glucose clamp at 12 to 16 mmol/L. Liver biopsy specimens and blood samples were taken before infusion and hourly. At 3 hr the liver was excised, stored for 24 hr at 1-degrees-C in University of Wisconsin solution and biopsied. It was then placed at 20-degrees-C for 1 hr to simulate the reimplantation stage of transplantation. Glycogen and nucleotide levels were measured, and results were corrected for starch in the University of Wisconsin solution. A 20% glucose infusion produced rapid hepatic glycogenation without side effects. Greater glycogenation was obtained with 20% fructose but at the cost of lactic acidosis and a fall in pH. A combination of 15% glucose and 5% fructose produced intermediary glycogenation without significant side effects. Galactose (20%) was less efficient than glucose alone. The addition of alanine and glutamine (20 mmol/L) did not significantly improve glycogenation. Metabolism of glycogen at 1-degrees-C did occur. Glycogen content fell 0.15% +/- 0.05% dry weight liver per hour during cold preservation and 5.49% +/- 2.15% per hour during ischemic rewarming. The rate of glycogen depletion during rewarming was dependent on the amount of glycogen available at the start of the period. Phosphorylated nucleotide levels were maintained at significantly higher levels in glycogenated livers. Periodic acid-Schiff staining showed a clear gradient of glycogenation maximal in zone 1 and minimal in zone 3. Rapid hepatic glycogenation is possible and beneficial in terms of maintaining adenine nucleotide levels in a large animal model.