Baish J W, Netti P A, Jain R K
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Microvasc Res. 1997 Mar;53(2):128-41. doi: 10.1006/mvre.1996.2005.
The growth of tumors and their response to treatment are determined by delivery of diffusible substances to cancer cells and hence by their blood supply. Relative to most normal tissues, tumor blood flow is highly heterogeneous. Several hypotheses have been postulated to explain this anomalous behavior of tumor microcirculation, but the underlying mechanisms for these heterogeneities are not fully understood. In this study we consider a potential source of nonuniformity in the blood flow: the enhanced fluid exchange between the vascular and interstitial space mediated by the high leakiness of tumor vessels which could lead to a coupling between vascular, transvascular, and interstitial fluid flow. A simple network model is presented to describe the basic features of flow through a network of permeable and compliant vessels embedded in an isotropic porous medium. Two vascular geometries are considered: a regular mesh of identical vessels and a pair of countercurrent vessels of equal diameter. In each case, the flow through each vessel of the network is described by Poiseuille's law; the transmural flow between the vessels and the external porous medium is governed by Starling's law; the fluid movement through the porous medium is described by Darcy's law; and the vessel wall is assumed to be elastic. Our results show that the behavior of microcirculation may be strongly modified as a result of vascular compliance and enhanced vascular leakiness of tumor vessels. We found not only that the vascular pressure generates the well-known, high central interstitial fluid pressure, but also that the elevated interstitial pressure in turn alters the vascular pressure distribution. These changes in vascular pressure distribution result in a modification of the blood flow pattern. As the leakiness and compliance of the vessels increase, the blood is diverted away from the center of the tumor to a more peripheral path. The clinical significance of these results is that drug delivery for chemotherapy and oxygenation needed for radiotherapy may well be hampered in the central region of the tumor, despite the presence of highly permeable vessels in these regions.
肿瘤的生长及其对治疗的反应取决于可扩散物质向癌细胞的输送，因此也取决于其血液供应。相对于大多数正常组织，肿瘤血流具有高度异质性。人们提出了几种假说来解释肿瘤微循环的这种异常行为，但这些异质性的潜在机制尚未完全了解。在本研究中，我们考虑了血流不均匀性的一个潜在来源：肿瘤血管的高渗漏性介导的血管与间质空间之间增强的液体交换，这可能导致血管、跨血管和间质液流之间的耦合。提出了一个简单的网络模型来描述通过嵌入各向同性多孔介质中的可渗透和顺应性血管网络的流动的基本特征。考虑了两种血管几何形状：相同血管的规则网格和一对等直径的逆流血管。在每种情况下，网络中每条血管的流动都由泊肃叶定律描述；血管与外部多孔介质之间的跨壁流动由斯塔林定律控制；通过多孔介质的流体运动由达西定律描述；并且假设血管壁是有弹性的。我们的结果表明，由于肿瘤血管的血管顺应性和血管渗漏性增强，微循环的行为可能会受到强烈影响。我们不仅发现血管压力会产生众所周知的高中心间质液压力，而且还发现升高的间质压力反过来会改变血管压力分布。这些血管压力分布的变化导致血流模式的改变。随着血管渗漏性和顺应性的增加，血液从肿瘤中心转移到更外围的路径。这些结果的临床意义在于，尽管肿瘤中心区域存在高渗透性血管，但化疗药物输送和放疗所需的氧合作用在肿瘤中心区域可能会受到严重阻碍。
