{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:45:09Z","timestamp":1775983509697,"version":"3.50.1"},"posted":{"date-parts":[[2025,6,3]]},"group-title":"Physiology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Electronic nicotine delivery systems (ENDS) heat \u201cE-liquids\u201d to generate \u201cE-vapor\u201d, an aerosolized mixture containing nicotine and flavors. Flavored ENDS are popular among teens who vape, however, the possible cardiac electrophysiological harm of inhalation exposure to flavored ENDS are not fully understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To test if inhalation exposure to flavoring carbonyls in E-liquids compromises mitochondrial integrity, increases oxidative stress, and leads to cardiac electrophysiological toxicity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Gas chromatography mass spectrometry (GC\/MS), flow cytometry, oxygen consumption rate (OCR) measurement, in-vivo programmed electrical stimulation (PES), and multielectrode array (MEA) were used in atrial like HL-1 myocytes, hiPSC derived cardiomyocytes, and mice overexpressing mitochondrial catalase (mCAT).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We compared the toxicity of E-vapor exposure from 30 differently flavored E-liquids in HL-1 cells using apoptotic annexin V flow cytometry. Most E-liquids were toxic. We identified the major flavoring carbonyls in these E-liquids and quantified their concentrations using GC\/MS. Linear regression analysis showed that toxicity correlated with carbonyls concentration. Using flow cytometry of CellROX and TMRE staining, HL-1 cells exposed to flavored E-vapor showed increased reactive oxygen species and depolarized mitochondrial membrane potential. Additionally, exposure decreased OCR in these cells. In-vivo inhalation exposure to flavored E-vapor increased the inducible ventricular tachycardia duration in WT but not in mCAT mice compared to controls. MEA recordings in hiPSC derived cardiomyocytes exposed to flavored E-vapor, with or without nicotine, resulted in changes in the spontaneous beating rate.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Inhalation exposure to flavored ENDS negatively affects ventricular electrophysiology, in part via adverse mitochondrial remodeling, and increased oxidative stress.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.31.657128","type":"posted-content","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:19:38Z","timestamp":1749014378000},"source":"Crossref","is-referenced-by-count":1,"title":["Oxidative stress mediates cardiac electrophysiological injury in inhalation exposure to flavored vaping products"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-8865","authenticated-orcid":false,"given":"Obada 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