The National Heart, Lung, and Blood Institute (NHLBI) awarded a $1,250,934 project grant under the Cardiovascular Diseases Research program (CFDA 93.837) to the Regents of the University of Michigan to conduct a multi-scale systems analysis of the metabolic and mechanical determinants of reserve cardiac power output. The overarching goal is to capture and test hypotheses on the mechanisms that determine physiological limitations to cardiac power and output reserve, and contribute to diminished left-ventricular power output and exercise intolerance in heart failure patients.
The research plan involves developing and refining a computational modeling framework to simulate whole-body exercise and cardiac energetics and mechanics, and applying this platform to integrate individual-specific data to assess the relative contributions of cardiac intrinsic versus peripheral factors in limiting exercise capacity. The research also aims to test hypotheses related to the capacity of the myocardium to maintain ATP, ADP, and Pi concentrations needed to support contraction and relaxation, and how impairments in this capacity may be linked to diminished cardiac mechanical work. A sub-award was made to Stichting Vumc (Uhp-Vumc) to conduct human subject experiments, including metabolic and functional characterization of various subject groups, cardiopulmonary exercise testing, and right heart catheterization exercise testing.
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