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Responses of tumor microcirculation (RBC flux) to i.p. glucose or mannitol injections were studied in early generation isotransplants of a spontaneous C3Hf/Sed mouse fibrosarcoma (FSaII). RBC flux in superficial tumor microregions was assessed using laser Doppler flowmetry. After administration of glucose or mannitol (a nonmetabolized sugar alcohol), a dose-dependent reduction in laser Doppler flow, and a dose-dependent increase in systemic hematocrit occurred concurrently. Maximum flow reductions induced by i.p. glucose or mannitol were statistically indistinguishable for equal osmotic load. Maximum decreases in RBC flux for glucose or mannitol were 20 and 25% (1.25 mg/g i.p.), 42 and 48% (2.5 mg/g i.p.), 72 and 60% (5 mg/g i.p.), and 80 and 75% (10 mg/g i.p.), respectively. Maximum increases in systemic hematocrit ranged from 18% (1.25 mg/g glucose i.p.) to 33% (10 mg/g glucose i.p.). Examination of RBC count, blood hemoglobin concentration, and fluid accumulation in the abdominal cavity after glucose or mannitol administration were all compatible with a significant shift of intravascular/extracellular water into the abdominal cavity with resultant systemic hypovolemic hemoconcentration. RBC volume and mean hemoglobin content of RBC remained unchanged with glucose loading. The data suggest that reductions in laser Doppler flow are predominantly caused by hypovolemic hemoconcentration following i.p. administration of hyperosmolar sugar solutions. Changes in laser Doppler flow due to specific glucose-mediated or glucose-related phenomena are probably of minor importance in the murine tumor system investigated. Future studies on murine tumors, examining for specific effects of glucose on metabolism and/or therapy, should not use i.p. administration of hyperosmolar solutions.

Tumor acidosis and energy deprivation enhance thermal sensitivity. We have used in vivo 31P nuclear magnetic resonance spectroscopy to noninvasively monitor changes in pH and energy metabolism in FSaII mouse tumors after i.p. administration of glucose. A dose of 5 g/kg glucose induced a pH drop of 0.31 units without any statistically significant change in energy status. The pH changes resolved within 2 h. In contrast, administration of 10 g/kg glucose resulted in a severe acidosis (mean nadir pH of 6.19 corresponding to a mean pH drop of 0.96 units) and loss of energy, the latter most probably being due to an acidosis-induced inhibition of glycolysis during ischemic hypoxia. The resulting acidosis and energy loss were more persistent and resolved in 5.5-28 h. In contrast, after an identical dose of mannitol (10 g/kg), a pH drop of approximately only 0.1 units over 72 min was noted. The data suggest that both cleavage of glucose to lactic acid and blood flow inhibition are involved in glucose induced tumor acidosis. In vivo 31P nuclear magnetic resonance spectroscopy may be useful clinically to monitor therapeutic attempts at enhancing thermal sensitivity.