Mechanical Study on Tumor Microvessel Damage Induced by Alternate Cooling and Heating Treatment

Temperatures lower or higher than the body temperature have been used to treat diseases for therapeutic purposes based on thermal effects on biological tissues, i.e. cryosurgery, hyperthermia or high temperature ablation. New treatment modality by combining cryotherapy with hyperthermia or high temperature ablation has been proposed for better therapeutic outcome [1]. Using nude mice dorsal skin fold tumor chamber, our previous experimental study found that vasculature damage caused by the alternate treatment (cooling at −10°C for 1/2 hour followed by heating at 42°C for another 1/2 hour) was much more serious as compared to that of cooling or heating alone. The structure of tumor microvessels was mostly ruptured and blood supply shut down. Fractures caused by thermal stresses were frequently found in arteries or tissues during cooling and thawing processes because of the temperature gradients and heterogeneous properties of the biological materials such as the thermal expansion coefficient, elasticity, etc. Thermal stresses in both freezing and heating were expected to be major factors that caused the vessel rupture. During the subsequent heating, blood reperfusion occurred in the vessels and blood flow rates increased evidently. The pressure gradient driven blood flow yielded stress on the vessel wall, which was often used as a rupture indicator. In the alternate cooling and heating treatment, mechanical stresses on microvessel wall resulted from blood flow may be another important factor causing vascular damage.