The long term objective of this application is the determination of the extent to which vasodilator drugs, employed at doses that can be used in humans, can induce clinically significant improvements in hyperthermic temperature distributions produced in applications of hyperthermia to deep-seated tumors in the pelvis and abdomen. The assumed mechanism through which such improvement would be obtained is vasodilator-induced reduction of the tumor perfusion rate and/or increase in perfusion rates in critical normal tissues. The long term objective will be pursued through investigation of the effects of the vasodilators hydralazine and sodium nitroprusside on perfusion rate (capillary blood flow) and hyperthermic temperature distributions in spontaneous, superficial and deep-seated trunk tumors and adjacent and neighboring normal tissues in random-source conditioned dogs. Perfusion rates in tumors and normal tissues will be measured with the radioactive microspheres technique. In each dog, microspheres containing four different gamma-emitting labels will be used to determine perfusion rates at normal and elevated temperatures, both in the absence and presence of vasodilator drugs. Interaction of consecutively established conditions in a given study will be minimized through placement of the two hyperthermia applications at the end of the four-condition experimental sequence, limitation of the time at target temperatures to ten minutes, and employment of """"""""no drug"""""""" tUmor temperatures of 42 degrees C or 43 degrees C, depending on the results of a temperature-seeking study conducted prior to initiation of the vasodilator drug studies. Hyperthermia will be administered to deep-seated tumors noniNvasively, with MAPA, a commercially available high frequency annular array electromagnetic applicator or with HELIOS, an experimental multibeam ultrasound device. Elevated temperature distributions produced both with and without vasodilators will be measured in tumor and adjacent, neighboring, remote and superficial normal tissues through """"""""pullback"""""""" of thermometer sensors along appropriately placed catheter tracks and/or through sampling of individual temperature sensors set in place at appropriate locations. Biopsy specimens will be taken prior to experimentation and autopsies will be performed to evaluate perfusion rates and hyperthermia-injury. Experiments will be conducted on 100 dogs over a five year period.
