ANALYSIS OF OXYGEN-TRANSPORT TO TUMOR-TISSUE BY MICROVASCULAR NETWORKS
ANALYSIS OF OXYGEN-TRANSPORT TO TUMOR-TISSUE BY MICROVASCULAR NETWORKS
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DOI：
10.1016/0360-3016(93)90070-c
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发表时间：
1993-02-15
影响因子：
7
通讯作者：
GROSS, JF
中科院分区：
文献类型：
--
作者：
SECOMB, TW;HSU, R;GROSS, JF
我们目前的理论模拟氧气输送到肿瘤组织的微血管网络，在体内观察血管的几何形状和血液流动的肿瘤微循环的基础上。这些研究的目的是研究血管几何形状对组织缺氧发生的影响。在大鼠背部皮瓣制备中，在两个玻璃板之间包含的组织（厚度200 μ m）中进行观察。引入乳腺腺癌（R3230 AC）并使其生长，绘制肿瘤中的微血管网络，提供每个节段中的长度、几何方向、直径和血流速度的数据。基于这些数据，对包含5个无分支血管节段的1 mm X 1 mm区域和包含22个节段的0.25 mm X 0.35 mm区域进行模拟。通常，假设血管位于玻璃板之间的平面中间，深度为100 μ m。血管中的流速基于测量的速度和直径。假设的组织耗氧率在一定范围内变化。使用绿色函数方法，计算组织区域中每个点的氧分压（PO2）。随着耗氧量增加，组织PO2福尔斯下降，缺氧首先出现在离最近血管相对较远的点。良好的氧合区域的宽度是由简单的分析预测。组织PO2的累积频率分布与具有相同血管密度的Krogh型模型的预测进行了比较，并且发现后一种方法假设血管的均匀间隔，可能低估了缺氧组织的程度。我们估计的最大消耗率，可以持续无组织缺氧大大低于从Krogh型模型获得的。我们的结论是肿瘤微循环的异质性结构可以对缺氧微区的发生有实质性的影响。
We present theoretical simulations of oxygen delivery to tumor tissues by networks of microvessels, based on in vivo observations of vascular geometry and blood flow in the tumor microcirculation. The aim of these studies is to investigate the impact of vascular geometry on the occurrence of tissue hypoxia. The observations were made in the tissue (thickness 200 mum) contained between two glass plates in a dorsal skin flap preparation in the rat. Mammary adenocarcinomas (R3230 AC) were introduced and allowed to grow, and networks of microvessels in the tumors were mapped, providing data on length, geometric orientation, diameter and blood velocity in each segment. Based on these data, simulations were made of a 1 mm X 1 mm region containing five unbranched vascular segments and a 0.25 mm X 0.35 mm region containing 22 segments. Generally, vessels were assumed to lie in the plane midway between the glass plates, at 100 mum depth. Flow rates in the vessels were based on measured velocities and diameters. The assumed rate of oxygen consumption in the tissue was varied over a range of values. Using a Green's function method, partial pressure of oxygen (PO2) was computed at each point in the tissue region. As oxygen consumption is increased, tissue PO2 falls, with hypoxia first appearing at points relatively distant from the nearest blood vessel. The width of the well-oxygenated region is comparable to that predicted by simpler analyses. Cumulative frequency distributions of tissue PO2 were compared with predictions of a Krogh-type model with the same vascular densities, and it was found that the latter approach, which assumes a uniform spacing of vessels, may underestimate the extent of the hypoxic tissue. Our estimates of the maximum consumption rate that can be sustained without tissue hypoxia were substantially lower than those obtained from the Krogh-type model. We conclude that the heterogeneous structure of tumor microcirculation can have a substantial effect on the occurrence of hypoxic micro-regions.