0000000000185488
AUTHOR
Matthew A. Kluge
Microcirculatory and pH Alterations in Isotransplanted Rat and Xenotransplanted Human Tumors Associated with Hyperthermia
The rationale for considering the use of hyperthermia as an antitumor agent is based on three different mechanisms of action depending on the hyperthermia levels chosen: At moderate hyperthermia levels (40°–42.5° C) heat can increase the radiosensitivity and/or the chemosensitivity. At higher tissue temperatures ( > 42.5° C) hyperthermia acts as a cytotoxic agent since mammalian cells die after heating in a temperature-, time-, and cell cycle-dependent manner. Besides direct effects on the cell membranes, on the cytoskeleton, on metabolic processes, on DNA replication, and on RNA and protein synthesis, indirect effects distinctly modulating the anticancer action of heat have to be considere…
Response of tumour red blood cell flux to hyperthermia and/or hyperglycaemia.
Laser Doppler flowmetry has been applied to subepidermal rat tumours during localized ultrasound hyperthermia and/or moderate, short-term hyperglycaemia. Blood glucose levels were elevated 4-fold by continuous i.v. infusion of D-glucose (4.8 g/kg/60 min). To determine whether the effects of hyperglycaemia on tumour blood flow involved increased rates of glycolysis and lactic acid production, galactose, a sugar not metabolized by the tumour, was administered using the same dose schedule. Hyperglycaemia was accompanied by a 3-fold increase in blood lactate levels and a slight hypervolaemic haemodilution without any significant systematic changes of the arterial blood pressure or respiratory b…
Tumour Blood Flow Following Local Ultrasound Heating Computed from Thermal Clearance Curves
Thermal clearance curves following termination of ultrasound-induced hyperthermia in human mammary carcinomas implanted into the flanks of nude rats were studied. They were found to be monoexponential in form, both with and without blood flow. From the difference between the inverse time constants with and without flow, the tumour blood flow rate could be calculated. Blood flow was found to increase with very short exposure times at the therapeutic hyperthermia temperature and subsequently decrease as the exposure time increased. A higher therapeutic hyperthermia temperature augmented this effect.
Laser Doppler flowmetry in subepidermal tumours and in normal skin of rats during localized ultrasound hyperthermia.
Laser Doppler flowmetry has been applied to normal skin and to subepidermal tumours during localized ultrasound hyperthermia in the rat. In normal skin, 40 degrees C hyperthermia only induced a marginal increase in the red blood cell flux. Significant increases occurred after 20 min at 42 degrees C and after 4 min at 44 degrees C. During 44 degrees C hyperthermia maximum fluxes were reached after 24 min. Thereafter, the flow declined and finally approached preheating values. In contrast, in subepidermal tumours 40 degrees C hyperthermia on the average induced a slight decrease of the flux. During 42 degrees C hyperthermia a significant flow decrease was found after 40 min of heating. Follow…
Pathophysiology of Tumors in Hyperthermia
The response of tumor cells to hyperthermia is critically influenced by a number of pathophysiological factors both in vitro and in vivo. The most relevant factors in this context are tumor blood flow, tissue oxygenation, the energy status, and the pH distribution, which in turn define the cellular microenvironment.