Cardiorespiratory and autonomic impacts of coolants in E-cigarette aerosols

The Department of Health and Human Services National Institutes of Health Office of the Director awarded the University of Louisville $782,293 on June 10, 2026, under the Family Smoking Prevention and Tobacco Control Act Regulatory Research program (CFDA 93.077, Project Grant R01HL185698).

The University of Louisville's Office of Research & Innovation will conduct research examining how coolants such as menthol, WS-3, and WS-23 used in electronic cigarettes alter cardiorespiratory and autonomic nervous system function. The project will use murine models with continuous electrocardiography, blood pressure, and pleural pressure telemetry to assess how coolants modify the acute and chronic effects of e-cigarette aerosols on cardiac electrophysiology, autonomic tone, ventilatory function, hemodynamics, and exposure to nicotine and aldehydes. The research will evaluate how coolant concentration and device power modulate these effects and will determine whether adolescent mice exhibit heightened susceptibility compared to adults, with attention to sex differences and persistence of cardiotoxicity after exposure ceases.

Work is performed in Louisville, Kentucky. The period of performance extends from June 10, 2026, to May 31, 2031. The assistance type is a Project Grant.

Abstract

Coolants such as menthol, WS-3, and WS-23 are widely used in electronic cigarettes (E-CIGS) to reduce irritation and enhance appeal-especially among youth. Despite their prevalence, the cardiopulmonary toxicity of these agents remains poorly characterized. Recent work shows that E-CIG aerosols can disrupt autonomic nervous system regulation and cardiac electrophysiology, increasing catecholamine release, enhancing sympathetic regulation of cardiac rhythm, and provoking arrhythmias. Proof is also mounting that nicotine's sympathomimetic traits mediate these pathogenic effects. Preliminary data from our laboratory show that coolants increase systemic nicotine levels, blunt respiratory reflexes, and potentiate arrhythmias upon exposures to E-cigarette aerosols, suggesting a paradoxical role for coolants in suppressing ventilatory responses while intensifying cardiovascular risk. These findings take on added significance in light of recent case reports of sudden cardiac arrest in young E-cigarette users, including some in otherwise healthy individuals. This project will elucidate how E-cigarette coolants alter exposure to harmful and potentially harmful constituents (HPHCS)-particularly nicotine and aldehydes-concurrent with their effects on cardiovascular and respiratory physiology. Using robust murine models with continuous ECG, blood pressure, and pleural pressure telemetry, we will assess how coolants alter the acute and chronic effects of E-cigarette aerosols on cardiac electrophysiology, autonomic tone, ventilatory function, hemodynamics, and toxicant exposure. We will also evaluate how coolant concentration and device power modulate these effects. In parallel, we will determine whether adolescent mice exhibit heightened susceptibility to these effects compared to adults, with attention to SEX differences and the persistence of cardiotoxicity after exposure cessation. This comprehensive, multi-modal approach incorporates novel protocols for arrhythmia inducibility, high-resolution physiologic monitoring, and complementary analyses of biomarkers of exposure and effect. By clarifying how coolants interact with HPHCS-especially nicotine and aldehydes-to drive cardiopulmonary injury across age and SEX, this work addresses high-priority research areas identified in RFA-OD-25-001, including the toxicological evaluation of E-cigarette constituents and their cardiopulmonary effects. The results will inform regulatory policy and public health strategies aimed at mitigating cardiovascular risk associated with E-cigarette use, particularly among vulnerable youth.