Warnke P C, Molnar P, Bigner D D, Heistad D H, Groothuis D R
Department of Neurology, Northwestern University Medical School, Evanston, IL.
Neurology. 1987 Dec;37(12):1870-3. doi: 10.1212/wnl.37.12.1870.
Adenosine was infused intravenously at 10 mumol/(kg.min) into athymic ("nude") rats with intracerebral D-54MG xenotransplanted brain tumors, in an attempt to increase tumor blood flow. Cerebral blood flow (F) was measured with 14C-iodoantipyrine and quantitative autoradiography. Mean arterial blood pressure was 95 +/- 9.4 (SE) mm Hg in the adenosine group and 112 +/- 6.0 mm Hg in the controls. Averaged mean whole tumor F was significantly higher in adenosine-treated brain tumors (117.6 +/- 20.8 ml/[hg.min]) than in controls (62.2 +/- 9.7 ml/[hg.min]). Regionally, there were significant increases of F in tumor periphery and brain around tumor, but not in tumor center or any tumor-free brain regions. Focal values of F less than 5 ml/(hg.min) were present in some necrotic regions of adenosine-treated tumors. These results, obtained in unanesthetized rats with transplanted gliomas from a human cell line, confirm our earlier observations in avian sarcoma virus-induced brain sarcomas in dogs, and suggest that adenosine or perhaps other vasodilators could be used to selectively increase the delivery of lipid-soluble chemotherapeutic drugs to brain tumors.
将腺苷以10 μmol/(kg·min)的剂量静脉输注到脑内移植了D-54MG异种移植脑肿瘤的无胸腺(“裸”)大鼠体内,试图增加肿瘤血流量。用14C-碘安替比林和定量放射自显影法测量脑血流量(F)。腺苷组的平均动脉血压为95±9.4(标准误)mmHg,对照组为112±6.0 mmHg。腺苷治疗的脑肿瘤的平均全肿瘤F(117.6±20.8 ml/[hg·min])显著高于对照组(62.2±9.7 ml/[hg·min])。在局部,肿瘤周边和肿瘤周围脑区的F显著增加,但肿瘤中心或任何无肿瘤脑区没有增加。腺苷治疗的肿瘤的一些坏死区域存在F的局部值低于5 ml/(hg·min)。这些在未麻醉的、移植了人细胞系胶质瘤的大鼠中获得的结果,证实了我们早期在犬类禽肉瘤病毒诱导的脑肉瘤中的观察结果,并表明腺苷或其他血管扩张剂可用于选择性增加脂溶性化疗药物向脑肿瘤的递送。