# Oxygen-guided supervised exercise therapy in peripheral artery disease.

> **NIH VA I21** · OMAHA VA  MEDICAL CENTER · 2024 · —

## Abstract

The long-term goal of our research is to improve mobility, functional independence, and quality of life in
patients with peripheral artery disease (PAD) by developing conservative interventions. PAD is a
manifestation of atherosclerosis, which produces blockages in the leg arteries, and results in insufficient blood
flow to the legs. PAD results in significant gait deficits and an overall sedentary lifestyle. Our prior work showed
that the biochemical (oxidative stress and mitochondrial dysfunction) and histological (myofiber degeneration
and fibrosis) characteristics of PAD muscles are altered compared to controls. These myopathic changes are
due to cycles of ischemia and reperfusion, and they correlate to functional limitations (walking distance and calf
muscle strength). Limb ischemia from PAD is the most common disorder treated within the vascular surgery
service of the Omaha Veterans Affairs Medical Center. The most effective treatment for increasing the distances
that patients with PAD can walk is supervised exercise therapy (SET). However, SET uses pain onset to guide
exercise intensity and rest cycles. These repeated bouts of ischemia/reperfusion could cause further pathological
damage to muscle myofibers and oxidative processes. Such adverse effects of ischemia may explain why not
all patients improve with SET. Preventing cycles of ischemia-reperfusion during SET can improve walking
performance without further muscle biochemistry damage in patients with PAD. We propose using hemodynamic
responses to modulate exercise intensity and prevent ischemia during SET. Muscle oxygen-guided supervised
exercise therapy (M-SET) can prevent ischemia onset and thus preserve muscle mass and function during
exercise therapy in patients with PAD. The aims are:
Aim 1: To determine the exercise outcomes of an M-SET versus a standard SET session in patients with
PAD. Aim 2: To determine the acute effect of M-SET versus standard SET on oxidative stress and
inflammation in patients with PAD. Aim 3: To determine the effect of 12 weeks of M-SET versus standard
SET on exercise outcomes, muscle biochemistry, and subject-reported preference in patients with PAD.
We will measure exercise outcomes during one session each of M-SET (using StO2 on the calf to modulate
exercise) and SET, in 12 patients with PAD using a cross-over design. Exercise outcomes will be assessed by
the total distance patients walked during the session, metabolic cost, metabolic equivalents of the task, physical
activity enjoyment, and rate of perceived exertion. In Aim 2, oxidative stress will be measured using peripheral
blood mononuclear cells before and after each exercise session (SET and M-SET) in all patients. During the
standard SET session, subjects will walk until claudication pain becomes severe and the participant needs to
stop. Then subjects will rest until claudication pain subsides. Afterward, subjects will walk again, repeating the
cycle for up to 50 minutes. M-SET will use an St...

## Key facts

- **NIH application ID:** 10799114
- **Project number:** 1I21RX004632-01A1
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Iraklis Ilias Pipinos
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799114

## Citation

> US National Institutes of Health, RePORTER application 10799114, Oxygen-guided supervised exercise therapy in peripheral artery disease. (1I21RX004632-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10799114. Licensed CC0.

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