# Intravenous oxygen microparticles for treatment of cardiac arrest

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $664,383

## Abstract

Project Summary/Abstract
A continuous supply of oxygen gas is required to maintain cellular structure and function. Even brief deficits in
oxygenation, as occurs in patients with lung injury or airway problems, can cause the heart to stop beating, a
disorder known as cardiac arrest. More than 200,000 patients per year in the US suffer from cardiac arrest in
the hospital setting (i.e. in-hospital cardiac arrest, IHCA). Among those, approximately ~40-60% are thought
to be precipitated by hypoxia (i.e. asphyxial cardiac arrest, or ACA), with a mortality rate between 70 and 95%,
and neurologic injury is common in survivors. In these patients, the rapid restoration of oxygen delivery to the
brain, heart, and other vital organs is paramount to intact survival. Delays of a few minutes can be the
difference between recovering back to health and permanent neurologic impairment. In the most critically ill
patients, underlying lung disease (for example) makes restoration of normal oxygen levels difficult. To address
this problem, we have developed a way to administer oxygen gas intravenously. The key to this
technology is that the oxygen gas is encapsulated within gas-filled microparticles small enough to pass through
the circulation without causing obstruction. The particle shell is composed of a biocompatible material,
modified dextran acetate succinate (DAS), which is stable for months in storage but releases gas immediately
upon contact with the pH of blood. In rodents with cardiac arrest provoked by hypoxemia (i.e. ACA), the
intravenous administration of oxygenated DAS (DAS-Ox) microparticles immediately restored oxygen levels to
near-normal. When normal ventilation was restored, all treated animals exhibited return of spontaneous
circulation (ROSC); all control animals died. We hypothesize that the early restoration of normal oxygen
tension using injections of intravenous oxygen will sustain myocardial and cerebral energy production in
asphyxial cardiac arrest, which will achieve early ROSC and improve neurologically intact survival.
This project has 3 specific aims. In Aim I, we will optimize the oxygen carrying capacity of DAS-Ox MPs in
order to minimize the volume of administration and mass of DAS polymer required to meaningfully supplement
the oxygen consumption of large animals. We will vary manufacturing parameters and chemical composition
of the shell within a design of experiments construct, examining shell thickness, particle size, dispersibility, and
rheology as endpoints. In Aim II, we will infuse optimized microparticles in swine to screen for pulmonary
vascular obstruction, rigorously examining for endothelial injury, interference with blood components, organ
injury, and describing biodistribution, redesigning the particle shell as needed. In Aim III, we will test whether
the administration of intravenous oxygen in a swine model of asphyxial cardiac arrest improves
neurologically intact survival. If successful, this work would create a pa...

## Key facts

- **NIH application ID:** 9989891
- **Project number:** 5R01HL141818-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** John Nagi Kheir
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $664,383
- **Award type:** 5
- **Project period:** 2018-09-15 → 2022-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989891

## Citation

> US National Institutes of Health, RePORTER application 9989891, Intravenous oxygen microparticles for treatment of cardiac arrest (5R01HL141818-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989891. Licensed CC0.

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