Laser Doppler flux and tissue oxygenation of experimental tumours upon local hyperthermia and/or hyperglycaemia

Summary

Laser Doppler fluxmetry and oxygen partial pressure (pO₂) histography have been applied to investigate the acute effects of hyperthermia (HT) and/or hyperglycaemia (HG) on microcirculatory function and tissue oxygenation of subcutaneous rat tumours growing on the dorsum of the hind foot. The experiments were performed to test whether, and to what extent, the two adjunct treatment modalities applied alone or in combination can modify these therapeutically relevant parameters. Local HT was performed in a saline bath (44°C) for 2 h; HG was induced by i.v. infusion of 40% glucose solution for 2.5 h (blood glucose levels: 35–40 mM, during heating). Laser Doppler flux (LDF) in superficial tumour tissue regions was recorded over the entire treatment period; tumourpO₂ distribution was evaluated immediately after termination of the treatment. HG alone reduced the average LDF signal to 18% of the baseline reading before treatment, but did not influence the tumour oxygenation status and the proportion ofpO₂ readings occurring in the radiobiologically hypoxic class (pO₂=O–2.5 mm Hg). This phenomenon is most probably due to the occurrence of the Crabtree effect (reduction of the O₂ consumption rate when excess glucose is available within a malignant tumour). Hyperthermia alone reduced LDF to approximately the same extent, and led to a rise in the number ofpO₂ readings in the hypoxic range with only minor changes in the averagepO₂. The combined treatment (HT/HG) neither increased the fraction of “hypoxic”pO₂ readings nor intensified the flow drop already present at the end of the tumour heating. It is thus concluded that under hyperglycaemia the oxygenation status of normothermic and heated tumours is maintained. It may therefore be hypothesized that hyperthermia in conjunction with hyperglycaemia might be a better “radiosensitizer” than hyperthermia alone.