Characterization of tissue morphology, angiogenesis, and temperature in the adaptive response of muscle tissue to chronic heating.

Previous investigations on the in vivo effects of chronic heat on tissue suggest a response whereby heated tissue temperatures decrease over time. This response occurred in conjunction with localized angiogenesis, which possibly contributed to the temperature decreases by increasing local perfusion and enhancing tissue heat transfer. Our own studies were the first to use a chronic heat source to heat tissue at initial interfacial temperatures between 40 degrees C and 46 degrees C. Initial temperatures above 45.3+/-2.2 degrees C caused necrosis of adjacent tissue. Through an adaptive response, the necrosis was removed by 7 weeks and replaced by a highly vascularized tissue capsule at 41.8+/-0.5 degrees C. The present study sought to characterize the spatial distribution, number of capillaries, and temperatures associated with this adaptive response. Heated and control muscle tissue sections were removed after 2, 4, and 7 weeks of heating at 0.08 W/cm2. Tissue layer thicknesses and capillary densities were measured and correlated with corresponding tissue temperatures. Necrosis was present adjacent to the heat source at 2 and 4 weeks; however by 7 weeks, a highly vascularized fibrous tissue capsule had replaced nearly all necrosis. Capillary densities, particularly near the heat source, were significantly greater at 7 weeks than at either 2 or 4 weeks. Capillary densities in heated tissue capillary fronts tripled from 2 to 7 weeks (106.4+/-14.3 caps/mm2 versus 39.1+/-18.5 caps/mm2). Furthermore, a mean temperature of 41.7+/-0.9 degrees C was measured in heated tissue capillary fronts at all durations, suggesting that this may be a threshold temperature for heat-induced angiogenesis or endothelial cell survival. These findings more completely characterize the perfusion component of the current mathematical model for heat transfer in tissue and will help to establish guidelines for the functional heat loss that an implantable, heat-producing device may allow.