In the proposed research Dr. Schmid-Schoenbein is concerned about blood flow in skeletal muscle and its engineering analysis. The long term objective is to develop a theory of transport in skeletal muscle which explains in full detail how nutrients are carried to the muscle cells, metabolites are controlled and under what conditions muscle is subject to injury by our own white blood cells. The PI's original objective was to develop a quantitative biomechanical model of the microcirculation in skeletal muscle as a keystone to an understanding of transport and organ function. In the past the following objectives were met: the micro-anatomy in a selected muscle was defined in a complete and quantitative way; the passive vessel and blood properties were established, and a new theory of blood flow was formulated and critically tested against independent microvascular and whole organ measurements. The PI now proposes to expand the scope of the theory to include myogenic autoregulation with experimental verification and a detailed analysis of leukocyte mediated microvascular resistance. Dr. Schmid-Schoenbein's previous theory and recent measurements showed a surprisingly high microvascular resistance in rat skeletal muscle perfused with deactivated granulocytes. More specific measurements for activated granulocytes and other leukocytes are needed in light of their importance in pathophysiology. The PI's approach constitutes a systematic analysis of microcirculation in skeletal muscle; it serves to unify numerous physiological observations, and it sets the basis for eventual analysis of problems in muscle exercise.
