Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte...

Experimental brain tumors were produced in cats by xenotransplantation of the rat glioma clone F98 into the white matter of the left hemisphere. One to 4 weeks after implantation, local adenosine triphosphate (ATP), glucose, lactate, and tissue pH were measured via imaging techniques in cryostat sections passing through the center of the tumor and correlated with changes in water and electrolyte content. The tumors exhibited a heterogeneous metabolic pattern, with a tendency for ATP to decrease and lactate to increase during tumor development. Tissue pH was above 7.5 in tumors with high ATP content but it sharply declined at low ATP levels. In peritumoral edema, ATP also decreased and lactate increased but, in contrast to tumor tissue, pH became more alkaline. Metabolic changes were associated with edema formation, as evidenced by the rise in water and sodium content. There was a distinct difference between tumor tissue and peritumoral edema: in tumor tissue, pH declined with increasing water content, whereas in peritumoral edema it increased. These observations are interpreted as follows: 1) in tumor tissue, "lactacidosis" and ATP depletion are attributed to disturbances in blood flow, resulting in metabolic failure and the intracellular "cytotoxic" accumulation of water; 2) in peritumoral edema, "lactalkalosis" is the result of an efflux of (alkaline) lactate salts from the tumor into the expanded extracellular compartment, and the decrease in ATP is the volumetric effect of extracellular "vasogenic" edema fluid and not the result of cellular energy failure. These findings are of importance for the interpretation of volume-selective magnetic resonance spectroscopy and may contribute to the establishment of spectroscopic criteria for the evaluation of therapeutical interventions.