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应用血管扩张剂药物后,实验性肿瘤的灌注和氧合无改善。

No improvement in perfusion and oxygenation of experimental tumors upon application of vasodilator drugs.

作者信息

Thews O, Kelleher D K, Vaupel P

机构信息

Institute of Physiology and Pathophysiology, University of Mainz, 55099 Mainz, Germany.

出版信息

Int J Oncol. 2001 Dec;19(6):1243-7. doi: 10.3892/ijo.19.6.1243.

Abstract

The oxygen deficiency seen in solid tumors is predominantly caused by an insufficient O2 supply as a result of inadequate tumor perfusion. The aim of this study was to analyze whether a number of vasodilator drugs might be suitable to increase tumor perfusion and consequently improve the oxygenation status of experimental tumors. Rats with s.c. DS-sarcomas were treated with either Na+-nitroprusside (7-25 microg x min(-1) x kg(-1) BW) or nifedipine (10 microg x min(-1) x kg(-1) BW). Red blood cell (RBC) flux was assessed continuously using laser-Doppler flowmetry and mean tumor pO2 was measured polarographically using O2-sensitive catheter electrodes. Systemic application of the vasodilator drugs resulted in a dose-dependent decrease in MABP. In parallel, tumor perfusion was reduced linearly with falling MABP resulting in a decrease in RBC flux by approximately 40%. Resistance to flow did not change during the infusion indicating that these drugs have no impact on tumor vessel diameter. With decreasing tumor perfusion, tumor pO2 was reduced parallel to the MABP drop. This effect was more distinct with Na+-nitroprusside than with nifedipine due to the more pronounced fall in MABP. The vasodilator drugs studied are not suitable for dilation of tumor vessels either because the tumor vasculature lacks contractile wall elements or because the vessels are already maximally dilated.

摘要

实体瘤中出现的缺氧主要是由于肿瘤灌注不足导致氧气供应不足所致。本研究的目的是分析一些血管扩张药物是否可能适合增加肿瘤灌注,从而改善实验性肿瘤的氧合状态。将患有皮下DS-肉瘤的大鼠用硝普钠(7 - 25微克×分钟(-1)×千克(-1)体重)或硝苯地平(10微克×分钟(-1)×千克(-1)体重)进行治疗。使用激光多普勒血流仪连续评估红细胞(RBC)通量,并使用对氧敏感的导管电极通过极谱法测量平均肿瘤pO2。血管扩张药物的全身应用导致平均动脉血压(MABP)呈剂量依赖性下降。同时,随着MABP下降,肿瘤灌注呈线性降低,导致红细胞通量下降约40%。在输注过程中血流阻力没有变化,表明这些药物对肿瘤血管直径没有影响。随着肿瘤灌注降低,肿瘤pO2与MABP下降平行降低。由于MABP下降更明显,硝普钠引起的这种效应比硝苯地平更显著。所研究的血管扩张药物不适合扩张肿瘤血管,要么是因为肿瘤血管系统缺乏收缩性壁成分,要么是因为血管已经处于最大扩张状态。

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