Less J R, Posner M C, Skalak T C, Wolmark N, Jain R K
Department of Surgery, University of Pittsburgh, Pennsylvania, USA.
Microcirculation. 1997 Mar;4(1):25-33. doi: 10.3109/10739689709148315.
To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood.
Human colorectal carcinomas (tissue weight = 272 g +/- 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular east that was used for measurement of vascular branching patterns and dimensions.
The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, zzero, was constant at approximately 6.5 x 10(9) g/cm3. Below 40 mm Hg, zzero increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar meshworks had mean segment diameters of 11 +/- 2 and 9.6 +/- 2 microns, lengths of 46 +/- 24 and 107 +/- 40 microns, and intercapillary distances of 46 +/- 13 and 74 +/- 24 microns, respectively.
The geometric flow resistance in neoplastic tissue is 1-2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressure exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.
测量人类结直肠癌中血流的几何阻力。尽管肿瘤血流在癌症的检测和治疗中都至关重要，但对肿瘤循环中血流的决定因素却知之甚少。
对人类结直肠癌（组织重量 = 272 g ± 43 g（标准差），n = 6）进行离体灌注，使用已知粘度的缓冲生理盐溶液，流速范围为2.5至40 ml/min，灌注压力为从8至100 mmHg。根据压力 - 流量曲线的斜率确定几何阻力。为了研究几何阻力的主要决定因素，即血管结构，其中一个肿瘤用巴特森17号聚合物灌注，并在氢氧化钾中浸软以制作阳性血管铸型，用于测量血管分支模式和尺寸。
在灌注压力高于40 mmHg时，压力 - 流量关系呈线性，几何阻力zzero在约6.5×10⁹ g/cm³时保持恒定。在40 mmHg以下，zzero迅速增加。人类结直肠癌的小动脉和毛细血管网络结构与实验性啮齿动物肿瘤相似。平面和非平面网络中的毛细血管平均节段直径分别为11 ± 2和9.6 ± 2微米，长度分别为46 ± 24和107 ± 40微米，毛细血管间距分别为46 ± 13和74 ± 24微米。
肿瘤组织中的几何流动阻力比正常组织中观察到的高1 - 2个数量级。功能性血管横截面积的减小可能解释了小灌注压力下阻力的额外增加。观察到的流动阻力可能是由于特殊的小动脉和毛细血管网络结构、增殖癌细胞施加的压力和/或血管内与血管外血流之间的耦合。这些观察结果表明，仅肿瘤血管情况可能并不表明流动阻力或肿瘤对血源性治疗药物的敏感性。
