Forker E L, Luxon B
Am J Physiol. 1978 Dec;235(6):E648-60. doi: 10.1152/ajpendo.1978.235.6.E648.
The conventional approach to estimating hepatic transfer coefficients from the plasma disappearance curve ignores the effects of blood flow in the splanchnic and peripheral circulations. The effect of these simplifying assumptions on derived estimates of the rate constants has never been studied. To examine this problem we have constructed a distributed model that takes account of intrahepatic concentration profiles, nonuniform blood-flow distribution in the sinusoids, and delayed mixing in the peripheral circulation. Solutions to the new model constructed by numerical inversion of the Laplace transform afford a comparison between the new model and the conventional one. The sensitivity of the conventional equations to experimental error has also been evaluated. The results indicate that conventional estimates of the rate constants for hepatic uptake and cell-to-plasma efflux are subject to a systematic underestimate, the errors increasing rapidly with the initial extraction fraction. Estimates of the uptake constant obtained from the initial slope are especially susceptible to circulatory distortions and proved unacceptable even at low values of the initial extraction fraction. The liver content at 3 min did not in general provide a reliable index to these errors. In contrast to these problems, the conventional model returns generally accurate estimates of the steady-state plasma clearance and the rate constant for excretion.
从血浆消失曲线估计肝脏转运系数的传统方法忽略了内脏和外周循环中血流的影响。这些简化假设对推导的速率常数估计值的影响从未得到研究。为了研究这个问题，我们构建了一个分布式模型，该模型考虑了肝内浓度分布、肝血窦内血流分布不均匀以及外周循环中的延迟混合。通过对拉普拉斯变换进行数值反演构建的新模型的解，使得新模型与传统模型之间能够进行比较。还评估了传统方程对实验误差的敏感性。结果表明，肝脏摄取和细胞到血浆外排的速率常数的传统估计值存在系统性低估，误差随着初始提取分数迅速增加。从初始斜率获得的摄取常数估计值特别容易受到循环扭曲的影响，即使在初始提取分数较低时也被证明是不可接受的。3分钟时的肝脏含量通常不能为这些误差提供可靠指标。与这些问题形成对比的是，传统模型通常能准确估计稳态血浆清除率和排泄速率常数。
