Pastor C M, Morel D R, Billiar T R
Division of Anesthesiological Investigations, University of Geneva, Switzerland.
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):796-802. doi: 10.1164/ajrccm.157.3.9609119.
To determine whether hepatic urea production is limited at low hepatic O2 delivery (DO2) by O2 itself or by the availability of substrate for urea synthesis, we isolated livers from normal rats and perfused them with Krebs-Henseleit bicarbonate (KHB) buffer, KHB + 5 mM NH4Cl, or KHB + 5 mM glutamine (Gln) as an NH3 donor. The pump flow was lowered in stages, and we determined at each flow rate inflow and outflow O2 content and urea levels in the outflow perfusate. Urea production in Gln-perfused livers remained constant at high DO2 and declined in direct proportion to DO2 below a critical oxygen delivery (DO2crit, the point below which the hepatic O2 consumption [VO2] becomes limited by the hepatic DO2). The DO2crit calculated from the urea release-DO2 relationship (147 +/- 32 microl/min/dry g) was similar to the DO2crit calculated from the VO2-DO2 relationship (158 +/- 26 microl/min/dry g). When Gln concentration and flow rate were maintained constant while decreasing PO2 in the inflow perfusate (as well as hepatic DO2), urea production declined below the DO2crit. Furthermore, when Gln concentration in the perfusate was gradually reduced while keeping hepatic DO2 constant, urea production decreased proportionally with Gln concentrations in the perfusate. Consequently, urea production is dependent on Gln and O2 availability and becomes limited at the same DO2crit determined by the VO2-DO2 relationship.
为了确定在低肝氧输送（DO2）时，肝脏尿素生成是受氧本身限制还是受尿素合成底物的可用性限制，我们从正常大鼠中分离出肝脏，并用 Krebs-Henseleit 碳酸氢盐（KHB）缓冲液、KHB + 5 mM 氯化铵或 KHB + 5 mM 谷氨酰胺（Gln）作为氨供体进行灌注。逐步降低泵流量，我们在每个流速下测定流入和流出的氧含量以及流出灌注液中的尿素水平。在高 DO2 时，用 Gln 灌注的肝脏中的尿素生成保持恒定，而在低于临界氧输送（DO2crit，即肝氧消耗[VO2]受肝 DO2 限制的点）时，尿素生成与 DO2 成比例下降。根据尿素释放-DO2 关系计算出的 DO2crit（147±32 微升/分钟/干克）与根据 VO2-DO2 关系计算出的 DO2crit（158±26 微升/分钟/干克）相似。当 Gln 浓度和流速保持恒定，同时降低流入灌注液中的 PO2（以及肝 DO2）时，尿素生成在 DO2crit 以下下降。此外，当灌注液中的 Gln 浓度逐渐降低，同时保持肝 DO2 恒定时，尿素生成与灌注液中的 Gln 浓度成比例下降。因此，尿素生成取决于 Gln 和氧的可用性，并在由 VO2-DO2 关系确定的相同 DO2crit 时受到限制。
