During the previously funded period(3/85-6/89) a fundamental new view of local tissue heat transfer has been developed which theoretically and experimentally indicates that the principal vascular elements involved in blood-tissue energy exchange in muscle tissue are the 100 to 500 mu m arteries and their counter current veins. A new bioheat equation has been derived to describe this energy exchange and a new model for peripheral tissue heat transfer proposed in which it is possible for the first time to quantitatively relate the heat transfer between blood and tissue to the local microvascular geometry and flow. In the proposed research we will develop a theoretical and conceptual framework in which this microvascular description can be used to relate changes in local tissue conductivity to the centrally and locally mediated changes in the vasomotor tone of the microcirculation. In the proposed research the local thermal modulation of alpha- and beta- adrenoceptor mediated control of microvascular heat transfer will be experimentally examined in muscle and the results interpreted using this new equation and peripheral tissue model. In particular, (i) a non-linear theory for the vasomotor regulation of microvascular heat transfer will be developed to explain the variety of hyperemic responses observed when mammalian muscle tissue is subjected to local heating; (ii) an experimental model based on the rat cremaster muscle preparation will be used to examine the thermal threshold and sensitivity, and the underlying physiology of branching arterioles and venules of the microvascular network subjected to both heating and cooling; (iii) pharmacological techniques will be used to examine the role of alpha 1, alpha 2 and beta 2 adrenoceptor mediated responses under hyper- and hypothermic conditions in the microvascular preparations described in (ii) above, and will be applied to the theory in (i) to model these responses; (iv) the rat tail will be used as a representative model for the mammalian extremity and human digit and the separate role of macro-and microvascular components in cutaneous heat transfer will be studied experimentally; (v) a detailed quantitative model for macro- and microvascular heat transfer in the mammalian extremity based on the vascular anatomy and axially varying flow in the rat tail experiments in (iv) will be developed; (vi) a new experimental microvascular model will be developed in which the heat transfer from vascular elements mu m in diameter can be individually examined to experimentally determine the role of blood flow and vessel size on local tissue conductivity, and thus test the predictions of the Weinbaum-Jiji equation for Keff. The proposed studies will have a significant impact upon both basic and applied problems in thermal physiology. The experimental quantification of heat transfer in less than 50 mu m vessels will yield the first data for vessels of this size class, and will permit evaluation of the large amount of theoretical work that has been carried out over the past 40 years. The proposed studies of hyperthermic hyperemia impact upon the improvement of the clinical use of hyperthermia in the treatment of cancer. The studies of heat transfer from the extremity extend current work and will further the development of better models of human thermoregulation which are applied to the treatment of hyper- and hypothermia and to problems of human exposure to extreme thermal environments such as outer space or industrial settings.
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