Temporary vascular occlusion and glucose: effects on tumour and normal tissue pH in animal experiments

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.