# Supplemental Oxygen for Pulmonary Embolism (SO-PE) - A Mechanistic Clinical Trial

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $568,519

## Abstract

Background: Acute pulmonary embolism (PE) can cause a sudden rise in pulmonary artery (PA) pressure
and right ventricular dysfunction (RVD), which can lead to circulatory collapse and death. Increased PA
pressure and RVD results from mechanical obstruction by thrombus, but also pulmonary artery (PA)
vasoconstriction. We have developed a validated porcine model of acute PE and found that, after experimental
induction of PE with RVD, supplemental oxygen rapidly and reproducibly reduces PA pressure by 50%.
However, it is not known how supplemental oxygen reduces PA pressure and RVD, nor is it known whether the
underlying mechanisms also apply to human patients. We hypothesize that oxygen affects RVD primarily by
relieving hypoxic pulmonary vasoconstriction and reducing PA pressure, and that this process is metabolically
driven. To study this hypothesis, we designed a mechanistic trial of supplemental oxygen in patients with acute
PE and a correlated study of PE in pigs. Setting: This study will be performed in the Massachusetts General
Hospital Emergency Department (MGH ED), Harvard Medical School (HMS), and Aarhus University, Denmark.
Patients with acute PE will be enrolled in the MGH ED by experienced clinical researchers with expertise in PE
and bedside echocardiography. At Aarhus University an experienced team of cardiologists and
anesthesiologists will perform experiments on our porcine model of PE with RVD. Metabolomics will be
performed by Metabolon and analyses will be performed at HMS. Research Plan: In the MGH ED, we will
perform a randomized, crossover trial of 80 human subjects with acute PE, evidence of RVD, and no baseline
hypoxemia. Patients will be randomized to breathe room air or 60% supplemental oxygen via facemask.
Therapy will be alternated at T=15, T=30, T=45 minutes, and then maintained for 180 minutes. After each
change and at 180 minutes, we will: 1) perform echocardiograms and calculate specific measurements to
identify the mechanisms by which supplemental oxygen changes PA pressure and RV function and, 2) draw
blood for agnostic metabolomic analyses and to test our a priori hypotheses that the regulation of
diacylglycerols, triacylglycerols, PC plasmalogens, TCA-cycle intermediates, acyl carnitines, and breakdown
products of branched-chain amino acids change with supplemental oxygen. At Aarhus University, we will
experimentally induce PE with RVD in 24 pigs. As in our human experiment, we will measure PA pressure, RV
function, and circulating metabolites. We will also assess changes in pulmonary perfusion and cardiac
metabolism associated with supplemental oxygen using dual-energy computed tomography and
hyperpolarized MRI. Relevance to Public Health: PE causes >100,000 annual deaths and is the third most
common cause of cardiovascular mortality in the U.S.. This project will decipher the underlying molecular and
pathogenic changes induced by supplemental oxygen in PE. Our study design is innovative, based on strong
precli...

## Key facts

- **NIH application ID:** 10918051
- **Project number:** 5R01HL168040-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** CHRISTOPHER KABRHEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $568,519
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918051

## Citation

> US National Institutes of Health, RePORTER application 10918051, Supplemental Oxygen for Pulmonary Embolism (SO-PE) - A Mechanistic Clinical Trial (5R01HL168040-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10918051. Licensed CC0.

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