Meyer, R. E., Braun, R. D., Rosner, G. L. and Dewhirst, M. W. Local 42°C Hyperthermia Improves Vascular Conductance of the R3230Ac Rat Mammary Adenocarcinoma during Sodium Nitroprusside Infusion.
The effect of sodium nitroprusside-induced hypotension on the perfusion of the R3230 adenocarcinoma during local 42°C hyperthermia was studied using a combination of intravital microscopy and laser Doppler flowmetry. Fischer 344 rats were implanted with dorsal skin flap window chambers containing the R3230Ac tumor and allocated to three treatment groups (34°C with nitroprusside, 42°C with nitroprusside, and 42°C with 0.9% saline). After baseline observation at 34°C, tumors were locally heated to 42°C using a water bath and either 0.9% saline or nitroprusside sufficient to reduce blood pressure 20% below pretreatment baseline was infused. Nitroprusside at 34°C decreased tumor vascular conductance 40% with no effect on the diameter of arterioles entering the tumor. The diameter of arterioles entering 42°C heated tumors increased 35% independent of blood pressure change. Saline at 42°C had no effect on tumor vascular conductance; however, nitroprusside at 42°C increased tumor vascular conductance 55%. Local 42°C tumor heating, combined with a moderate reduction in blood pressure with nitroprusside, overrides the vascular steal effect associated with reduced perfusion pressure alone and results in improved tumor perfusion. Observations of the effect of vasodilator substances on normothermic tumor perfusion cannot be extrapolated to situations where moderate hyperthermia is used.