# Systematic identification of cardiotoxic e-cigarette flavorants

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2024 · $79,055

## Abstract

Parent Grant Abstract. The use of e-cigarettes (e-cigs) has increased substantially since they were first
introduced in 2003. E-cig devices aerosolize e-liquids that typically consist of humectants with variable levels of
nicotine and flavoring chemicals. Although there are thousands of commercially available flavor mixtures, they
routinely overlap in individual flavor chemicals (flavorants), which are far fewer in number. Many of these
flavorants belong to common chemical classes and are generally recognized as safe for ingestion. However,
their direct and indirect cardiac effects following heating and inhalation, particularly in combination with nicotine,
remain mostly unknown. Direct exposure to nicotine alone distinctly affects the cardiac action potential waveform,
potentially contributing to the high incidence of arrhythmias and sudden cardiac death among smokers. Recent
evidence also suggests that nicotine in e-cigs may similarly promote adverse cardiac outcomes. Yet, the
influence of flavorants on the cardiac effects of e-cig aerosols remains untested. In our ongoing work, we found
that exposure to nicotine-containing e-cig aerosols of various flavors acutely and differentially altered the
electrocardiogram (ECG) in mice, variably inducing QT interval prolongation, increasing heart rate, and evoking
arrhythmia. As well, two separate e-liquids with the same characterizing flavorant consistently increased
ventricular arrhythmias. Furthermore, we observed in cardiomyocytes that treatment with several flavorants
common to e-cigs directly altered contractility, rhythmicity, and action potential duration. Nonetheless, it remains
unknown how individual flavorants in e-cig aerosols exert direct or indirect cardiac effects in vivo. Considering
the growing popularity of e-cigarettes and the urgent need for studying the in vivo toxicological profile of
constituents in these products, we propose to test the hypothesis that e-cigarette flavorants modify the effects of
e-cig aerosol exposures on cardiac electrophysiology, leading to arrhythmias and functional remodeling of the
heart. To test this, we will systematically identify both acute and long-term effects of flavorant exposure on cardiac
electrophysiology using a combination of state-of-the-art in vivo, in vitro, and ex vivo approaches. Specifically,
we will: 1) Identify the acute effects of flavored e-cig aerosol inhalation on cardiac electrophysiology in
vivo, 2) Examine the direct impact of flavorants on cardiac electrophysiology in vitro and ex vivo, and,
3) Elucidate deleterious impacts of acute and chronic flavorant aerosol exposure on cardiac
electrophysiology, structure, and function. These studies, which are responsive to the research priorities of
the FDA/CTP, will provide new data showing how different flavor chemicals affect cardiac excitability and
potentially promote arrhythmogenesis. Such results would aid in formulating policies regulating the manufacture,
distribution and marketi...

## Key facts

- **NIH application ID:** 11089952
- **Project number:** 3R01HL163818-03S1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Alex Perrow Carll
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,055
- **Award type:** 3
- **Project period:** 2022-04-22 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089952

## Citation

> US National Institutes of Health, RePORTER application 11089952, Systematic identification of cardiotoxic e-cigarette flavorants (3R01HL163818-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11089952. Licensed CC0.

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