van de Merwe S A, van den Berg-Blok A E, Kroon B B, van der Zee J, van den Berg A P
Department of Radiotherapy, Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Int J Hyperthermia. 1995 Nov-Dec;11(6):829-39. doi: 10.3109/02656739509052339.
The relationship between duration of a period of vascular occlusion and magnitude of pH decrease in tumour and normal tissue was investigated in rats. To acidify tissue pH further, moderate dose glucose (2.4-3.0 g.kg(-1).hr(-1)) was administered intravenously through a catheter positioned in a tail vein, immediately after the clamp was released. This sequence of pH modifying modalities was chosen since it is employed in clinical regional isolation perfusion for recurrence of malignant melanoma of the limbs. Tumour pH in rat rhabdomyosarcoma BA1112 decreased more than normal tissue pH under 10, 20, 30 or 60 min of temporary vascular occlusion. Administration of glucose following any period of clamping always decreased tumour pH further. The largest pH decrease (0.29 pH units) was obtained after 30 min of clamping followed by 60 min glucose and 60 min saline infusion. In the clinic the combination of a maximum of 30 min of clamping followed by moderate dose glucose infusion, which can decrease tumour pH effectively, can be easily achieved in the setting of regional isolation perfusion. It can be used for treatment modalities that are known to be enhanced at lowered tissue pH, such as hyperthermia and certain chemotherapeutic drugs. These results form the basis for studying the therapeutic gain which can be obtained with this model.
在大鼠中研究了血管闭塞期持续时间与肿瘤及正常组织pH值下降幅度之间的关系。为了进一步酸化组织pH值，在松开血管夹后，立即通过置于尾静脉的导管静脉注射中等剂量的葡萄糖（2.4 - 3.0 g·kg⁻¹·hr⁻¹）。选择这种pH调节方式的顺序是因为它用于临床肢体恶性黑色素瘤复发的区域隔离灌注。在10、20、30或60分钟的临时血管闭塞情况下，大鼠横纹肌肉瘤BA1112的肿瘤pH值下降比正常组织pH值下降更多。在任何时间段的夹闭后给予葡萄糖总是会进一步降低肿瘤pH值。在夹闭30分钟后接着输注60分钟葡萄糖和60分钟生理盐水后，pH值下降最大（0.29个pH单位）。在临床上，在区域隔离灌注的情况下，可以很容易地实现最多夹闭30分钟然后输注中等剂量葡萄糖的联合操作，这可以有效降低肿瘤pH值。它可用于已知在较低组织pH值时增强疗效的治疗方式，如热疗和某些化疗药物。这些结果为研究通过该模型可获得的治疗增益奠定了基础。
