# Development of a Porcine Model of Carbon Monoxide Poisoning to Evaluate Cardiac and Mitochondrial Dysfunction

> **NIH NIH R03** · UNIVERSITY OF PENNSYLVANIA · 2020 · $74,817

## Abstract

Carbon monoxide (CO) is a colorless and odorless gas that is an important cause of poisoning annually
with an estimated 50,000 emergency department visits occurring in the US and it is a leading cause of
poisoning death globally. Various sources include faulty heat generators, suicidal attempts and fires. It is
estimated that CO poisoning in the US results in over $1 billion annually related to hospital costs and lost
earnings. CO poisoning has high mortality and morbidity with effects at the cardiovascular and neurologic
system. The most serious complication of consequential CO exposure is delayed neurological sequela which
occurs in up to 50% of survivors. However, the cardiac sequalae is less defined as well as the underlying
cellular dysfunction that may occur. Our own work demonstrates that there are alterations in mitochondrial
function (both bioenergetic and dynamic) in CO poisoning. The standard treatment for CO poisoning
recommended by the Undersea & Hyperbaric Medical Society is hyperbaric oxygen (HBO) therapy. At this
time, both diagnostics and treatments are aimed at early supportive care and select use of hyperbaric therapy.
There is significant debate with currently available biomarkers and treatment for CO poisoning requiring a new
approach to therapy that is mechanism-driven. Based on these existing gaps, there are ongoing investigations
for improved treatment based primarily on small animal studies. However, many agencies that oversee
toxicological testing require use of both rodent and non-rodent species which is lacking at this time. There is a
paucity of large animal models to study both cellular dysfunction and potential therapy in CO poisoning.
 The primary limitations that this R03 proposal seeks to address are the following: (1) limited mechanistic
understanding at a cellular level with regard to mitochondrial function (bioenergetics and dynamics); (2) the
adverse cardiovascular effects of CO poisoning and the underlying cellular dysfunction that may occur; (3) the
lack of adequate large animal models that more closely mimic human physiology.
 We propose to develop a large animal model of CO poisoning using the domestic pig (Sus scrofa
domesticus). The pig may be considered a translational model of biomedical research because of anatomical,
physiological and biochemical similarity to humans. This R03 proposal is strongly supported by preliminary
data and feasibility that will ensure success. The PI (Jang) currently holds a NHLBI K08 award and will
specifically leverage his K-supported research skills and techniques focused in the area of mitochondrial
medicine with the full support of both his departmental chair (Ben Sun, MD) and K08 mentor (Todd Kilbaugh,
MD) along with the outstanding environment that incorporates state-of-the-art equipment. The data and
methods obtained with this R03 award will allow the PI to submit a competitive R01 as an ESI.

## Key facts

- **NIH application ID:** 10063393
- **Project number:** 1R03HL154232-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DAVID H JANG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,817
- **Award type:** 1
- **Project period:** 2020-08-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063393

## Citation

> US National Institutes of Health, RePORTER application 10063393, Development of a Porcine Model of Carbon Monoxide Poisoning to Evaluate Cardiac and Mitochondrial Dysfunction (1R03HL154232-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10063393. Licensed CC0.

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