# Non-invasive imaging of reactive oxygen species in reperfusion injury myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $733,239

## Abstract

Project Summary
Coronary heart disease is the leading cause of death worldwide. Patients are treated with clot-busting drugs
(thrombolytic therapy) or the artery is reopened with a catheter (percutaneous coronary intervention), but,
paradoxically, restoration of blood flow to the heart muscle can cause additional injury that limits the success of
these procedures. Reperfusion injury appears to be a cascade of events, initiated by coronary artery
extravasation (hemorrhage), culminating in a failure to restore myocardial perfusion and leading to cell death
among viable cardiomyocytes in the peri-infarct region. It may be a predictor of long-term adverse clinical
outcomes or provide a therapy-modifiable target in patients with myocardial infarction. Imaging methods
specific to the molecular mechanisms of reperfusion injury would improve clinical care and our scientific
understanding of this disease. We hypothesize that iron is a catalyst for reactive oxygen species production in
reperfused myocardial infarction. We propose a series of experiments to investigate the association between
iron and reactive oxygen species using iron-sensitive magnetic resonance imaging and positron emission
tomography. We will validate these in vivo non-invasive imaging modalities with a battery of pathology,
immunohistochemistry, and spectrometry techniques in a large animal model. In Aim 1, we will investigate the
association between reactive oxygen species, iron and severity of infarction using MRI and PET. In Aim 2, we
will determine the extent of association between imaging markers of reperfusion injury and remodeling of the
left ventricle weeks after injury. This study will give a new understanding of the spatiotemporal relationships of
reactive oxygen species in the sub-acute and chronic period of myocardial infarction wound healing. This will
lead to studies in large animal models and humans that can evaluate therapies targeting imaging biomarkers of
reperfusion injury.

## Key facts

- **NIH application ID:** 10866595
- **Project number:** 5R01HL169378-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PACO E. BRAVO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $733,239
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866595

## Citation

> US National Institutes of Health, RePORTER application 10866595, Non-invasive imaging of reactive oxygen species in reperfusion injury myocardial infarction (5R01HL169378-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10866595. Licensed CC0.

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