Experimental transplantation gliomas in the adult cat brain

Abstract

Experimental brain tumours were produced in adult cats by stereotactic xenotransplantation of the rat glioma clone F98. Regional ATP, glucose and lactate were measured after 2-4 weeks on coronal cryostat sections by substrate-induced bioluminescence, potassium content was imaged by the histochemical sodium cobaltinitrite method, and regional pH by incubating cryostat sections with the fluorescent pH-indicator umbelliferone. The regional biochemical alterations were correlated with magnetic resonance imaging and tissue water content. Biochemical changes were heterogeneous in tumours but exhibited a rather uniform pattern in peritumoural oedema. ATP was consistently reduced, glucose and lactate were increased and pH was more alkaline than in normal white matter. The decrease of ATP matched the increase of water, indicating that ATP decline represents fractional dilution in the oedematous tissue rather than break-down of energy metabolism. The increased lactate levels, therefore, may originate from the tumour and not from a metabolic disturbance in the peritumoural oedematous tissue. The implications of this interpretation for the pathogenesis of peritumoural oedema are discussed.

Effect of extracorporeal life support on cerebral blood flow, metabolism and electrophysiology in normothermic cats

“…The preservation of energy and pH homeostasis despite increased lactate, resembles the metabolic situation of "lactalkalosis" in well-perfused regions of brain tumors [29]. As long as glycolysis is able to compensate for the hypoxia-induced reduction of oxidative energy yield, the ATP-dependent ion pumps are able to maintain a normal transmembrane sodium gradient which, in turn, drives the Na § + antiporter required to control intracellular pH.…”

Bioluminescence and fluoroscopic imaging of tissue pH and metabolites in experimental brain tumors of cat

“…The high *lactate is explained by an admixture of tumor-derived lactate salts to the edema fluid. 4 The low ATP and high lactate content of peritumoral edema, therefore, do not reflect a state of tissue hypoxia.…”

The pathophysiology of experimental brain edema

“…Tissue water correlates inversely with ATP and directly with lactate and glucose ( Figure 8). The slope of the correlation between ATP and water reveals that the percentual decrease of ATP matches precisely the increase of water content [32]. The decline of tissue ATP, in consequence, is not due to a disturbance of the energy metabolism but represents the fractional dilution of this (intracellular) substrate in the edematous tissue.…”

“…The metabolic changes induced by peritumorous edema were studied by bioluminescent and fluoroscopic techniques which allow a pictorial evaluation of metabolites and pH on intact cryostat sections [32] (Figure 7). Biochemical changes are heterogenous in tumors but exhibit a rather uniform pattern in peritumoral edema.…”