In previous experiments, we have shown that ventricles or pumping chambers constructed from canine latissimus dorsi muscle are capable of generating stroke work greater than the animal's own right ventricle but less than that of the left ventricle for at least several weeks. In this five-year research proposal, we plan to continue evaluation of skeletal muscle ventricles (SMVs) connected to various types of mock circulation devices during chronic studies. We plan to determine the optimal filling pressures that these SMVs will operate at chronically. We plan to determine through mathematical modeling which SMV designs or geometric configurations will result in the optimal power outputs. Phosphorus-NMR will be used to study energy utilization of the SMVs at various time intervals and levels of pump function. Intramural blood flow of the SMVs will be measured at various time intervals and at various levels of SMV function to determine at what levels of function ischemia might be occurring. Long-term studies will be conducted to determine SMV functional capacities up to one year. As SMV models are developed that function longer and with improved power ouput, then experiments will be conducted in which both latissimus dorsi muscles from the same animal are used so that both function simultaneously as SMVs - a situation analogous to a heart with two ventricles. As this research plan progresses, certain SMVs will be activated with custom-made implantable R-wave synchronous burst stimulators that can be programmed to fire in synchrony with the animal's own heart: every beat (1:1), 1:2, 1:3, etc. Thus by the end of this five year project, the capabilities of the canine latissimus dorsi SMV should be well-defined, thus setting the stage for chronic incirculation experiments. Professor Salmons, University of Liverpool, will contribute to this project by performing biochemical, histochemical and immunochemical evaluations of muscle biopsies from the SMVs. His group will also conduct a complementary research program on fundamental aspects of muscle mechanics that relate to this project.
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