Viscous resistance to blood flow in solid tumors: effect of hematocrit on intratumor blood viscosity.
Viscous resistance to blood flow in solid tumors: effect of hematocrit on intratumor blood viscosity.
复制标题
DOI：
--
复制
发表时间：
1989-07
期刊：
影响因子：
11.2
通讯作者：
E. Sevick;Rakesh K. Jain
中科院分区：
文献类型：
--
作者：
E. Sevick;Rakesh K. Jain
血管网络中的血液流速与动静脉压差成正比，与几何阻力和粘性阻力成反比。我们最近已经表明，血流的几何阻力随着肿瘤大小的增加和/或动脉压的降低而增加。在本研究中，通过用Krebs-Henseleit溶液和红细胞悬液（血细胞比容在1 - 60%之间）离体交替灌注乳腺癌[R3230 AC; N = 12;肿瘤重量，2.2 +/- 1.6（SD）g]，测定肿瘤微血管内血液流动的粘性阻力。我们的结果表明：（a）肿瘤内血液粘度随着血细胞比容的增加而增加;和（B）对于10 - 60%的固定血细胞比容，与使用锥/板粘度计在460 s-1的剪切速率下测量的体积粘度相比，肿瘤内血液粘度显著降低（P小于0.0001）。然而，这种瘤内血液粘度的降低并不像之前的骨骼肌研究那样明显。进一步比较显示，随着动脉压降低，肿瘤内血液粘度以比正常组织更高的速率和更低的血细胞比容增加。我们将肿瘤微血管中增加的粘性阻力归因于（a）不太明显的Fahraeus效应（即，小血管中血细胞比容的降低）和不太明显的Fahraeus-Lindqvist效应（即，与正常微血管相比在扩张的肿瘤微血管中小血管中血液粘度的降低）;（B）低剪切速率（即，与肿瘤血管相关的流速梯度），这可能在中等压力下甚至在低血细胞比容下促进红细胞叠连形成;和（c）5-14%的血管流体损失，这也可能增加微血管血细胞比容。我们还提出，由于体内存在WBC和癌细胞，体内肿瘤内血液粘度可能甚至高于离体血液粘度;这些细胞比RBC刚性大得多，可能导致肿瘤中粘性阻力增加和短暂的血管淤滞。这些结果在肿瘤血流调制使用化学和物理制剂的影响进行了讨论。
Blood flow rate in a vascular network is proportional to the arteriovenous pressure difference and inversely proportional to the geometric and viscous resistances. We have recently shown that the geometric resistance to blood flow increases with increasing tumor size and/or decreasing arterial pressure. In this study, the viscous resistance to blood flow within tumor microvasculature was determined by alternately perfusing mammary adenocarcinoma [R3230AC; N = 12; tumor weight, 2.2 +/- 1.6 (SD) g] ex vivo with Krebs-Henseleit solution and with RBC suspensions at hematocrits between 1 and 60%. Our results demonstrate that: (a) intratumor blood viscosity increases with increasing hematocrit; and (b) for fixed hematocrits between 10 and 60%, the intratumor blood viscosity is significantly reduced (P less than 0.0001) compared to bulk viscosity measured at shear rates of 460 s-1 using a cone/plate viscometer. However, this reduction of intratumor blood viscosity is not as pronounced as in a previous study of skeletal muscle. Further comparison shows that as arterial pressure is lowered, intratumor blood viscosity increases at a greater rate and at lower hematocrits than in normal tissues. We attribute the increased viscous resistance in tumor microvasculature to (a) a less pronounced Fahraeus effect (i.e., reduction in hematocrit in small vessels) and a less pronounced Fahraeus-Lindqvist effect (i.e., reduction in blood viscosity in small vessels) in dilated tumor microvessels compared to normal microvessels; (b) low shear rates (i.e., velocity gradients) associated with tumor vessels which may facilitate rouleaux formation at moderate pressures and even at low hematocrits; and (c) vascular fluid losses of 5-14% which may also increase microvessel hematocrit. We also propose that intratumor blood viscosity may be even higher in vivo than ex vivo due to the presence of WBC and cancer cells in vivo; considerably more rigid than RBC, these cells may cause increased viscous resistance and transient vascular stasis in tumors. The implications of these results in tumor blood flow modulation using chemical and physical agents are discussed.