# Muscle and physical function recovery after acute critical illness

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $414,738

## Abstract

Many patients who survive critical illness, including sepsis and acute respiratory failure, have arduous
recoveries plagued by an inability to recover muscle and physical function after hospital discharge, resulting in
lower quality of life, inability to return to work and disability. The number of patients surviving critical illnesses in
the United States continues to rise each year and therefore it is critically important to develop interventions that
will support their recovery. Clinical and muscle cellular factors driving skeletal muscle dysfunction are relatively
unknown after an acute critical illness, but are necessary to inform intervention development. We will address
this knowledge gap by studying myofibrillar and collagen protein turnover, cellular signaling pathways, and
markers of damage, inflammation and immune response in the first year of recovery. The unique aspect of this
proposal is the serial, intra-patient muscle tissue sampling paired with simultaneously obtained clinical
functional parameters over the first year of recovery post hospital discharge. Physical function and quality of
life outcomes will be assessed to understand why some patients recover muscle function, yet others develop
severe disability. The overall goal of this clinical observational study is to elucidate the cellular environment
and the patient’s clinical characteristics contributing to failed muscle recovery and physical disability in
survivors of critical illness. Our central hypothesis is that alterations in myofibrillar, mitochondrial and collagen
protein homeostasis are underlying muscle and physical dysfunction in patients surviving critical illness. In Aim
1, we will identify trajectory of recovery for muscle strength and power, as well as physical function in patients
surviving ICU-related critical illness including pneumonia, sepsis, and COVID-19 etiologies. We hypothesize
that patients with a higher initial severity of illness will show poor recovery of muscle strength and physical
function during the first year of recovery. In Aim 2, we will determine mechanisms of skeletal muscle
deficiencies contributing to disparate recovery in patients surviving ICU-related COVID-19 or other acute lung
injury etiologies. We hypothesize that patients with longer ICU durations will show poor recovery of muscle size
and increased collagen deposition during the first year of recovery. In addition, we hypothesize that patients
with persistent weakness and fatigue have prolonged impairments in mitochondrial function compared to
patients who recover their muscle function. Finally, we hypothesize that patients with long-term disability have
an inability to recover muscle function due to a cellular environment of that is not permissive to a positive
protein balance. We will use stable isotope mass spectroscopy measurements of muscle biopsies to determine
synthesis of myofibrillar, mitochondrial and collagen protein. Findings from this study, will inform why some
pat...

## Key facts

- **NIH application ID:** 10930804
- **Project number:** 5R01AR081002-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Esther E Dupont-Versteegden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $414,738
- **Award type:** 5
- **Project period:** 2023-09-18 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930804

## Citation

> US National Institutes of Health, RePORTER application 10930804, Muscle and physical function recovery after acute critical illness (5R01AR081002-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10930804. Licensed CC0.

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