Muscle tissue is abundantly endowed with vessels and interstitial fluid spaces in close proximity to the solid components of the tissue. These fluid compartments must affect the mechanical responses of the tissue. In addition to arteriosclerosis that affects perfusion of skeletal and heart tissue, many other diseases such as hypertension, diabetes, renal failure and heart failure result in an abnormal amount of fluid in vessel walls and/or the muscles of many organ systems. Some of the mechanical dysfunction of these organs is attributable to these fluid abnormalities. Therefore, it is important to elucidate the roles of the fluid in these two compartments in the biomechanical responses of muscles. We propose a combined theoretical and experimental approach to address this goal. The first step is to appropriately quantify the mechanical properties of the solid portion of the muscle. We have developed the requisite experimental and theoretical tools for this quantification for many types of soft tissues -- including both heart and skeletal muscles. The theoretical foundation for examining solid-fluid interactions is based on mixture theory. We recently formulated a modified mixture theory that, by using velocity rather than pressure boundary conditions, circumvents serious problems with existing approaches. We solved the problem of a uniaxially loaded perfused slab. With this background we can now directly address our goal. We will first extend our theory to anisotropic materials and test the predictions with experimental data from a slab of stretched, perfused canine diaphragm -- a mode specifically developed for this purpose. Concurrently, we will perform studies in both passive and actively contracting diaphragm to test our presumption that the fluid in the more mobile vasculature and that in the larger but less mobile interstitium contribute differently to the mechanical responses. For example, we will test the presumption that volume effects in both compartments play a role in the elastic and viscoelastic responses of passive muscle. Additionally, because flow is much slower in the interstitium than the vasculature, flow effects in the vasculature will dominate -- especially during contraction when interstitial volume effects are presumably minimized. If this dominance of vascular over interstitial flow is borne out, we will then extend our mixture theory to a solid and two fluid compartments -- in which volume effects of both compartments are important but flow effects of only one compartment are accounted for. This combined approach should not only provide mechanistic insight into muscle mechanics, and hence organ function, but may also lead to better diagnostic and therapeutic approaches for a wide spectrum of diseases in which fluid abnormalities in the walls of tissues play an important pathophysiologic role.
