Heat dissipation and its effects on tissue and blood interfaces are common problems associated with the development and increased use of total artificial hearts (TAHs) and many cardiac assist devices. The objective of this research is to investigate the effects of chronic heating on tissues and on blood-surface interactions. Elucidating the mechanisms of heat responses at device/tissue and blood/surface interfaces will allow for the establishment of thermal design criteria for these devices. Our previous work has shown that lung and muscle can adapt to chronic heat provided that the temperature is below a critical value. After the tissues have adapted, the upper limit for heat-flux dissipation is 0.08 W/cm2 for lung and 0.06 W/cm2 for muscle corresponding to a maximum surface temperature of 43 degree Centigrade. Morphometric and immunohistochemical analyses indicated the occurrence of significant angiogenesis and the development of thermo-tolerance in heated tissues. The next step is to determine the mechanisms of adaptation at both the tissue and cellular levels. Furthermore, because most TAHs and cardiac assist devices dissipate heat into the blood through the pump surface, the effects of heat on blood- surface interactions must be studied. The specific aims of this proposed program are as follows: (l) To investigate the effects of heat on blood and on the development of thermo-tolerance in tissue repair cells. In vitro tests will be used to identify the thermal limits for normal function and to characterize the thermo-tolerance occurring in cells. (2) To elucidate the mechanisms by which the tissue adapts to chronic heating. In vivo studies will be used to obtain the spatial and temporal changes in tissue temperature and to correlate these with-the corresponding cellular changes throughout the heated tissue. (3)To examine the effects of heat on acute and chronic blood-surface interactions using ex vivo and in vivo studies, respectively. Mathematical models of the in vitro, ex vivo, and in vivo systems will be developed to help design experiments, interpret the data, elucidate the mechanisms, and predict responses under conditions that are not evaluated experimentally.