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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Application of the dispersion model for description of the outflow dilution profiles of noneliminated reference indicators in rat liver perfusion studies.
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Application of the dispersion model for description of the outflow dilution profiles of noneliminated reference indicators in rat liver perfusion studies.

机译：弥散模型在描述大鼠肝灌注研究中未消除参考指标的流出稀释曲线中的应用。

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The dispersion model (DM) is a stochastic model describing the distribution of blood-borne substances within organ vascular beds. It is based on assumptions of concurrent convective and random-walk (pseudodiffusive) movements in the direction of flow, and is characterized by the mean transit time (t) and the dispersion number (inverse Peclet number), DN. The model is used with either closed (reflective) boundary conditions at the inflow and the outflow point (Danckwerts conditions) or a closed condition at the inflow and an open (transparent) condition at the outflow (mixed conditions). The appropriateness of DM was assessed with outflow data from single-pass perfused rat liver multiple indicator dilution (MID) experiments, with varying lengths of the inflow and outflow catheters. The studies were performed by injection, of bolus doses of 51Crlabeled red blood cells (vascular indicator), 125I-labeled albumin and [14C] sucrose (interstitual indicators), and [3H]2O (whole tissue indicator) into the portal vein at a perfusion rate of 12 ml/ min. The outflow profiles based on the DM were convolved with the transport function of the catheters, then fitted to the data. A fairly good fit was obtained for most of the MID curve, with the exception of the late-in-time data (prolonged tail) beyond 3 x [symbol: see text]. The fitted DNS were found to differ among the indicators, and not with the length of the inflow and outflow catheters. But the differences disappeared when a delay parameter, t0 = 4.1 +/- 0.7 sec (x +/- SD), was included as an additional fitted parameter for all of the indicators except water. Using the short catheters, the average DN for the model with delay was 0.31 +/- 0.13 for closed and 0.22 +/- 0.07 for mixed boundary conditions, for all reference indicators. Mean transit times and the variances of the fitted distributions were always smaller than the experimental ones (on average, by 6.8 +/- 3.7% and 58 +/- 19%, respectively). In conclusion, the DM is a reasonable descriptor of dispersion for the early-in-time data and not the late-in-time data. The existence of a common DN for all noneliminated reference indicators suggests that intrahepatic dispersion depends only on the geometry of the vasculature rather than the diffusional processes. The role of the nonsinusoidal ("large") vessels can be partly represented by a simple delay.
机译：扩散模型（DM）是描述器官血管床内血源性物质分布的随机模型。它是基于对流方向上同时对流和随机游走（伪扩散）运动的假设，并以平均渡越时间（t）和弥散数（反向佩克雷特数）DN为特征。该模型与流入和流出点的封闭（反射）边界条件（Danckwerts条件）一起使用，或者流入时的封闭条件与流出处的开放（透明）条件（混合条件）一起使用。 DM的适用性通过单次灌注大鼠肝脏多指示剂稀释（MID）实验的流出数据评估，其中流入和流出导管的长度不同。这些研究是通过在静脉内向门静脉注射大剂量的51Cr标记的红细胞（血管指示剂），125I标记的白蛋白和[14C]蔗糖（组织指示剂）和[3H] 2O（整个组织指示剂）进行的。灌注速度为12 ml / min。将基于DM的流出曲线与导管的输送功能进行卷积，然后拟合到数据中。对于大多数MID曲线，获得了相当不错的拟合，但最新的数据（尾部延长）超过3 x [符号：参见文本]。发现所安装的DNS在指标之间有所不同，并且与流入和流出导管的长度无关。但是，当将延迟参数t0 = 4.1 +/- 0.7秒（x +/- SD）用作除水以外的所有其他指标的附加拟合参数时，差异消失了。对于所有参考指标，使用短导管时，延迟模型的平均DN在闭合时为0.31 +/- 0.13，在混合边界条件下为0.22 +/- 0.07。平均通过时间和拟合分布的方差总是小于实验值（平均分别为6.8 +/- 3.7％和58 +/- 19％）。总之，DM是早期数据而非延迟数据的合理分散描述。所有未消除的参考指标均存在共同的DN，表明肝内扩散仅取决于脉管系统的几何形状，而不取决于扩散过程。非正弦（“大”）血管的作用可以部分通过简单的延迟来表示。

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