# Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure with Preserved Ejection Fraction

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $20,289

## Abstract

PROJECT SUMMARY
 Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the heart
failure population in the United States, and the primary chronic symptom experienced by these patients is
severe exercise intolerance. Exercise intolerance is quantified as reduced peak oxygen uptake during
exercise, and to date, therapies targeting central cardiac limitations have invariably failed to improve peak VO2,
quality of life, or survival in HFpEF. Emerging evidence from our lab suggests reduced skeletal muscle
oxidative capacity may contribute to exercise intolerance in HFpEF patients. However, the mechanisms
responsible for peripheral metabolic inefficiency remain unclear. Reduced blood flow (oxygen delivery), and
slowed oxygen uptake kinetics (O2 utilization), may be primary contributors to reduced skeletal muscle
oxidative capacity and result in the production of metabolites known to activate muscle afferent nerves and
stimulate reflex increases in muscle sympathetic (vasoconstrictor) nervous system activity (MSNA). Elevated
MSNA can in turn, result in further impairments in hemodynamic control during exercise. However, to date
there have been no studies specifically investigating the contribution of peripheral vascular, metabolic, and
neural impairments to reduced exercise capacity in HFpEF. The first goal of this proposal will be to identify
impairments in peripheral vascular, metabolic, and sympathetic neural function in HFpEF. To accomplish this,
we will measure the dynamic blood flow response (oxygen delivery) and oxygen uptake kinetics (oxygen
utilization) during knee extensor (KE) exercise, as well as MSNA during exercise to characterize the
contribution of peripheral abnormalities to exercise intolerance in HFpEF. The second goal will be to utilize
small muscle mass KE training, specifically targeting these peripheral skeletal muscle deficiencies, to improve
aerobic capacity and exercise tolerance in HFpEF. We will assess vascular, metabolic, and neural function
before and after completing 8 weeks of single KE exercise training, in conjunction with measures of maximal
aerobic capacity and functional capacity. The isolated KE training approach will minimize the central
hemodynamic stress of whole body exercise, while simultaneously targeting skeletal muscle function to
improve exercise tolerance in HFpEF. Importantly, this proposal will advance our understanding of the basic
pathophysiology of exercise intolerance in HFpEF. Considering that vascular function, oxidative capacity, and
a MSNA are independent predictors of mortality in heart failure patients, strategies aimed at improving these
functional markers may have important implications for the treatment of HFpEF, a condition for which there are
currently no known therapies to reduce morbidity and mortality.

## Key facts

- **NIH application ID:** 10266745
- **Project number:** 5F32HL137285-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Christopher M Hearon
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $20,289
- **Award type:** 5
- **Project period:** 2017-05-15 → 2020-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266745

## Citation

> US National Institutes of Health, RePORTER application 10266745, Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure with Preserved Ejection Fraction (5F32HL137285-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10266745. Licensed CC0.

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