# Multi-Scale Systems Analysis of Metabolic and Mechanical Determinants of Reserve Cardiac Power Output

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $625,467

## Abstract

Title:
Multi-Scale Systems Analysis of Metabolic and Mechanical Determinants of Reserve Cardiac Power
Output
Abstract:
Exercise capacity, a central factor in determining quality of life in healthy aging as well as
cardiovascular disease, is determined by a systems-level interaction of factors that are intrinsic to the
heart and myocardium and factors that are extrinsic to the heart. Cardiac intrinsic factors include the
metabolic power supply and mechanical pumping power of the myocardium. Extrinsic factors include
the capacity of the peripheral vasculature to vasodilate in response to increasing demands of exercising
musculature and the autonomic chemo- and baroreflexes. The overarching goals of this proposal are 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 (LVPO) and
exercise intolerance in heart failure (HF). The research plan uses a computational modeling approach
to simulate whole-body cardiovascular function, driven by a multi-scale model of myocardial
metabolism and mechanics, to analyze data from a battery of phenotyping assessments applied to
healthy control subjects and heart failure patients. The first aim of this proposal is to develop and refine
the multi-scale framework for simulating whole-body exercise and cardiac energetics and mechanics in
humans. This platform will be applied to integrate individual-specific data for testing and refinement of
hypotheses in Aims 2 and 3. Subject-specific model parameterization will be used to: (1.) assess the
relative contributions of cardiac intrinsic versus peripheral factors in limiting exercise capacity in heart
healthy control and failure subjects; (2.) test the hypothesis that the capacity of the myocardium to do
mechanical work is limited by its capacity to maintain ATP and its hydrolysis products ADP and Pi at
concentrations needed to support contraction and relaxation; and (3.) test the hypothesis that in
patients with impaired capacity to maintain these concentrations at physiological levels, this impairment
is causally linked to a diminished capacity of the myocardium to do mechanical work.

## Key facts

- **NIH application ID:** 10858888
- **Project number:** 1R01HL173346-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** DANIEL A BEARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,467
- **Award type:** 1
- **Project period:** 2024-06-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858888

## Citation

> US National Institutes of Health, RePORTER application 10858888, Multi-Scale Systems Analysis of Metabolic and Mechanical Determinants of Reserve Cardiac Power Output (1R01HL173346-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10858888. Licensed CC0.

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