# Ultrasound-mediated Controlled Hypoxemic Reperfusion for Inhibition of Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2020 · $739,145

## Abstract

PROJECT SUMMARY/ABSTRACT
Myocardial infarction is induced by an ischemic event and often leads to damage of the myocardium and
potentially death. Approximately 150,000 deaths occur each year in the United States due to acute myocardial
infarction and a similar number go on to suffer from debilitating heart failure due to the infarction. The primary
clinical goal during treatment of myocardial infarction is to restore blood flow to the myocardium as quickly as
possible. However, paradoxically, the reperfusion can cause significant damage to the myocardium. Of the
total infarcted volume, potentially up to 50% can be attributed to reperfusion and not ischemia. The
reperfusion injury occurs, in part, due to the ischemic tissue converting the newfound supply of oxygen into
reactive oxygen species. Reactive oxygen species can significantly damage a cell and lead to cell death. This
project will develop an ultrasound-based oxygen scavenging approach to enable controlled hypoxemic
reperfusion in order to reduce cell death from reactive oxygen species. The technique relies on a process
known as acoustic droplet vaporization, where a liquid droplet is phase-transitioned into a gas microbubble
when exposed to ultrasound. The microbubble acts a sink for oxygen in whole blood, effectively sequestering
the oxygen within the microbubble so that less oxygen diffuses into the tissue. In turn, less oxygen in the tissue
may reduce oxidative stress and cell death. Our central hypothesis is that ultrasound-mediated oxygen
scavenging during reperfusion, following an ischemic event, increases cell and tissue viability. In vitro cell
culture and ex vivo tissue models of ischemia-reperfusion injury have been used to obtain preliminary data
supporting this hypothesis. Our proof-of-principle data demonstrates that oxygen scavenging can be done
using intravascular ultrasound devices, which simplifies in vivo ultrasound targeting and would allow for a
percutaneous approach that can be integrated into existing percutaneous treatments. We have also
demonstrated the ability to tune the amount of oxygen scavenging by modifying droplet properties, droplet
concentrations, and ultrasound insonation parameters. We will test the hypothesis through studies focusing on
the efficiency and efficacy of oxygen scavenging in vitro, ex vivo, and in vivo. The first aim is to adapt our
current technology into a translationally relevant working system. Studies will investigate droplet manufacturing
and ultrasound insonation approaches. The second aim will investigate how the magnitude and duration of
oxygen scavenging effect reperfusion injury using an isolated whole heart with Langendorff preparation that
enables measurement of both infarct size and ventricular function. These protocols will be translated to an in
vivo porcine model of ischemia-reperfusion injury. The primary outcomes within that model will include infarct
size measurement and oximetry. The progression of these experiments wil...

## Key facts

- **NIH application ID:** 9947995
- **Project number:** 5R01HL148451-02
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Kevin Joseph Haworth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $739,145
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947995

## Citation

> US National Institutes of Health, RePORTER application 9947995, Ultrasound-mediated Controlled Hypoxemic Reperfusion for Inhibition of Reperfusion Injury (5R01HL148451-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9947995. Licensed CC0.

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