Dewhirst M W, Ong E T, Klitzman B, Secomb T W, Vinuya R Z, Dodge R, Brizel D, Gross J F
Division of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
Radiat Res. 1992 May;130(2):171-82.
Fischer 344 rats with R3230 Ac mammary carcinomas implanted in dorsal flap window chambers served as a model to obtain measurements of perivascular and stromal oxygen tension in normal and tumor tissues using Whalen recessed-tip microelectrodes (3- to 6-microns tip). Perivascular measurements were made adjacent to vessels with continuous blood flow. Thus the measurements and models provided are reflective of conditions leading to chronic hypoxia. Perivascular oxygen tensions averaged 72 +/- 13 mmHg in normal tissue vessels adjacent to tumor, 26 +/- 5 mmHg in tumor periphery, and 12 +/- 3 mmHg in tumor central vessels. There was a significant trend toward lower perivascular oxygen tensions in the tumor center (Kruskal-Wallis test, P = 0.002). A similar tendency was seen with a limited number of stromal measurements. Krogh cylinder models, which incorporate these data for perivascular oxygen tension, along with morphometric data obtained from the same tumor model suggest that hypoxic regions will exist between tumor vessels in the tumor center unless O2 consumption rates are well below 0.6 ml/100 g/min. The low perivascular measurements observed near the tumor center combined with the theoretical considerations suggest, for this model at least, that tissue oxygenation may best be improved by increasing red cell velocity and input pO2 and reducing oxygen consumption. The low perivascular oxygen tensions observed near the center also suggest that conditions conducive to increased red cell rigidity exist, that drugs which can decrease red cell rigidity could improve tumor blood flow and oxygenation, and that the endothelium of those vessels may be susceptible to hypoxia-reoxygenation injury.
将R3230 Ac乳腺癌植入背侧皮瓣窗口小室的Fischer 344大鼠作为模型,使用Whalen凹尖微电极(尖端3至6微米)测量正常组织和肿瘤组织中血管周围和间质的氧张力。在有持续血流的血管附近进行血管周围测量。因此,所提供的测量和模型反映了导致慢性缺氧的情况。肿瘤附近正常组织血管的血管周围氧张力平均为72±13 mmHg,肿瘤周边为26±5 mmHg,肿瘤中心血管为12±3 mmHg。肿瘤中心的血管周围氧张力有显著降低的趋势(Kruskal-Wallis检验,P = 0.002)。在有限数量的间质测量中也观察到类似趋势。Krogh圆柱体模型结合了这些血管周围氧张力数据以及从同一肿瘤模型获得的形态学数据,表明除非氧消耗率远低于0.6 ml/100 g/min,肿瘤中心的肿瘤血管之间将存在缺氧区域。肿瘤中心附近观察到的低血管周围测量值与理论考虑相结合,至少对于该模型而言,表明通过提高红细胞速度和输入pO2以及降低氧消耗可能最有效地改善组织氧合。在中心附近观察到的低血管周围氧张力还表明存在有利于红细胞刚性增加的条件,能够降低红细胞刚性的药物可以改善肿瘤血流和氧合,并且这些血管的内皮可能易受缺氧-再氧合损伤。