Ackermann R H, Bässler K H, Wagner K
Infusionsther Klin Ernahr. 1975 Feb;2(1):9-15.
During continuous infusions of 24--48 hours, glycerol utilization and turnover capacity in rats were estimated in a range from physiological to toxic doses. Total clearance, elimination constant, half life, transfer and pool size were calculated for various rates of infusion as well as for the endogenous turnover. With increasing blood level, the turnover rate rises like an enzyme saturation curve, first rapidly and then ever more slowly to a maximum value. Therefore, the steady state blood levels do not increase linearly with the infusion rate. The renal excretion of glycerol is below 1 per cent of the supply up to rates of infusion of 0.4g with kg-1 with h-1. Even beyond the upper limit of the metabolic turnover a steady state is reached due to the high renal excretion. Beginning with 2 mumol/ml the excretion rises linearly with the blood level. At rates higher than 0.5g with kg-1 with h-1 the individual differences of the steady state levels are high. A significant negative correlation between the steady state levels of glycerol in blood and the activity of glycerol kinase in the liver and kidneys was observed. Necroses of the renal tubuli were found at infusion rates exceeding the turnover capacity in animals with low enzyme activity. The conclusions which may be drawn from these data regarding the parenteral supply of energy-yielding substrates are discussed.
在持续输注24至48小时的过程中,对大鼠甘油利用和周转能力进行了评估,输注剂量范围从生理剂量到中毒剂量。计算了不同输注速率以及内源性周转情况下的总清除率、消除常数、半衰期、转运和池大小。随着血药浓度升高,周转率像酶饱和曲线一样上升,先是迅速上升,然后越来越缓慢,直至达到最大值。因此,稳态血药浓度不会随输注速率呈线性增加。在输注速率为0.4g·kg⁻¹·h⁻¹以下时,甘油的肾排泄量低于供应量的1%。即使超过代谢周转的上限,由于肾排泄量高,仍可达到稳态。从2μmol/ml开始,排泄量随血药浓度呈线性增加。在输注速率高于0.5g·kg⁻¹·h⁻¹时,稳态水平的个体差异很大。观察到血液中甘油的稳态水平与肝脏和肾脏中甘油激酶的活性之间存在显著的负相关。在酶活性低的动物中,当输注速率超过周转能力时,发现肾小管坏死。讨论了从这些数据中得出的关于胃肠外供应产能量底物的结论。