Changes in microregional perfusion, oxygenation, ATP and lactate distribution in subcutaneous rat tumours upon water-filtered IR-A hyperthermia

Abstract

The effect of hyperthermia on microcirculatory and metabolic parameters in s.c. DS-sarcomas of different sizes on the hind foot dorsum of SD-rats was investigated. Hyperthermia was carried out using a novel water-filtered, infrared-A radiation technique. Heating was performed at a rate of 0.5 degrees C/min until 44 degrees C was achieved in the tumour centre, which was maintained for 60 min. Using a multichannel laser Doppler flowmeter, red blood cell flux could be assessed continuously and at several sites within the tumour tissue simultaneously. Substantial inter-site variations in laser Doppler flux (LDF) were observed during hyperthermia which were independent of tumour size, site of measurement, and temperature at the site of measurement, indicating that single site measurements of tumour LDF are poor predictors of the mean response of a tumour to hyperthermia. When mean LDF was considered, decreases in red blood cell fluxes occurred that were more pronounced the greater the tumour volume. In no case was vascular stasis observed. Hyperthermia did not affect tumour oxygenation substantially. Microregional and global assessment of lactate and ATP concentrations demonstrated increased lactate and decreased ATP levels following hyperthermia. Tumour glucose levels were increased following hyperthermia, possibly due to an enlarged distribution space resulting from development of interstitial oedema. Changes in lactate and ATP levels and the lack of changes in tumour oxygenation suggest a modification of energy metabolism following hyperthermia in the form of increased ATP hydrolysis, intensified glycolysis and impaired oxidative phosphorylation.

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

“…In the literature, HT has been reported to have distinctly heterogeneous effects on tumour blood flow, whereby this variability may be at least partially explained by the use of different heating protocols in tumours with different histologies. In the DS-sarcoma used in the present study, HT has previously been shown to have a bimodal effect on tumour blood flow with an initial increase in perfusion of up to 20% being followed by a decrease down to 25% of pretreatment values (Kelleher et al, 1995). Microvascular damage, which in some instances can even result in blood flow stasis, has frequently been seen following PDT (Reed et al, 1988;Fingar et al, 2000;Dolmans et al, 2002).…”

“…Other potential factors that might be involved in the pronounced potentiation of the antitumour effects seen are a concerted action of PDT and HT on certain proteins or supramolecular structures (Prinsze et al, 1991) or a conversion of PDT-induced repairable lesions to irreparable lesions upon HT treatment (Chen et al, 2001). Additionally, increased lactic acid formation during HT, as has already been reported for this tumour model (Kelleher et al, 1995), may also result in a lower pH in tumour tissue, and since acidosis has been found to enhance the efficacy of ALA-PDT in vitro (Wyld et al, 1998), such metabolic changes within the tumour tissue may play a role in the effects of ALA-PDT þ HT.…”

“…Once a tumour volume of 0.6 -0.8 ml had been attained (6 -8 days after tumour implantation), the animals were anaesthetised with sodium pentobarbital (40 mg kg À1 i.p., Narcoren s , Merial, Germany) and randomly allocated to the various experimental groups, the details of which are summarised in Table 1. A radiation delivery system was used which has been described in detail previously (Vaupel et al, 1992;Kelleher et al, 1995Kelleher et al, , 1999. The light source in this system is a halogen lamp (24 V/150 W, type HLX64643, Osram, Germany) that emits over the spectral range from 420 to 1400 nm.…”

“…The water-filtered infrared component allows (at the same radiant flux density on a given surface) for longer exposure times and higher heat doses. Therapeutically relevant heating of tissue layers at a depth of up to 1.2 cm has been found to be possible with this system and the pattern of temperature gradients achieved has been described (Vaupel et al, 1992;Kelleher et al, 1995). The application of HT in this study (groups V and VI) involved the additional use of a feedback control system, where the temperature in the tumour centre was measured with needle-type thermocouples (f 250 mm; type 2ABAc, Philips, Germany) and the tumours heated at a rate of 0.41C min À1 to a set temperature of 431C (tumour centre) using the radiation source.…”

Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion

“…Details of this method have been described earlier by Kelleher et al (1995Kelleher et al ( , 1998b. This method uses the Doppler shift (i.e.…”