Direct demonstration of instabilities in oxygen concentrations within the extravascular compartment of an experimental tumor

Direct demonstration of instabilities in oxygen concentrations within the extravascular compartment of an experimental tumor
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DOI:
10.1158/0008-5472.can-03-2958
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发表时间:
2006-02-15
期刊:
影响因子:
11.2
通讯作者:
Dewhirst, MW
Dewhirst, MW
中科院分区:
医学1区
文献类型:
--
作者:
Lanzen, J;Braun, RD;Dewhirst, MW

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为了验证微血管红细胞流量的时间变化导致肿瘤间质中氧水平不稳定的假设,使用凹尖极谱微电极测量了生长在皮肤折叠窗腔中的R3230Ac乳腺肿瘤的血管外氧合。用荧光标记的红细胞测量Po(2)测量部位周围微血管中的红细胞流量。在所有实验中都观察到了时间Po(2)不稳定性。中位数Po(2)与距微血管的径向距离呈负相关。除了在氧扩散距离极限(140微米)附近的一个实验中,Po(2)的波动为<2 mm Hg,中位数Po(2)为<5 mm Hg外,在10 mm Hg以上和10 mm Hg以下的瞬时波动是一致的。在这些实验中没有发现血管停滞。这些结果表明,红细胞流量的波动,而不是血管停滞,可以导致Po(2)的时间变化,从血管周围区域延伸到最大氧气扩散距离。
To test the hypothesis that temporal variations in microvessel red cell flux cause unstable oxygen levels in tumor interstitium, extravascular oxygenation of R3230Ac mammary tumors grown in skin-fold window chambers was measured using recessed tip polarographic microelectrodes. Red cell fluxes in microvessels surrounding pO(2) measurement locations were measured using fluorescently labeled red cells. Temporal pO(2) instability was observed in all experiments. Median pO(2) was inversely related to radial distance from microvessels. Transient fluctuations above and below 10 mm Hg were consistently seen, except in one experiment near the oxygen diffusion distance limit (140 mu m) where pO(2) fluctuations were < 2 mm Hg and median pO(2) was < 5 mm Hg. Vascular stasis was not seen in these experiments. These results show that fluctuations in red cell flux, as opposed to vascular stasis, can cause temporal variations in pO(2) that extend from perivascular regions to the maximum oxygen diffusion distance.