Factors governing hyperthermia-induced pH changes in Yoshida sarcomas.

The impact of various factors modulating the acidification of tumour tissue upon localized ultrasound hyperthermia (1.7 MHz) at 44 degrees C for 60 min was investigated. Yoshida sarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Frequency distributions of tumour tissue pH values were measured with miniaturized needle glass pH electrodes (diameter of the sensitive tip: 650 microns). During normothermia the average tumour pH is 6.87 +/- 0.21. No relationship is found between tumour pH and tumour size (range: 0.6-5.4 g). A pH gradient exists from the tumour periphery (0.5-3.5 mm) to more central tissue layers (7.5-10.5 mm; delta pH = 0.17). During hyperthermia with heating-up rates greater than 1.5 degree C/min, mean tumour pH drops to 6.71 +/- 0.20 considering all tumours. The pH reduction observed is size-dependent being most pronounced in medium-sized tumours (wet weights around 2.4 g, delta pH = 0.26). Using the same tumour sizes, but heating-up rates less than 0.7 degree C/min, the tissue acidification is more severe (delta pH = 0.40). To a small extent, pH changes also depend on the tumour region investigated (e.g. central vs. peripheral tissue layers) leading to a flattening of the pH gradient from the tumour shell to the centre during heat treatment. During hyperthermia an interstitial oedema occurs, being mostly marked in small tumours (around 1.4 g). Considering systemic changes, a transient increase in perfusion pressure (leading to a change in blood flow), as well as a slight elevation of blood glucose levels (leading to a higher glucose supply), during hyperthermia may contribute to the pH drop.