{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:04:45Z","timestamp":1776791085106,"version":"3.51.2"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Luzhou Science and Technology Program","award":["2025JBH001"],"award-info":[{"award-number":["2025JBH001"]}]},{"name":"Sichuan Science and Technology Program","award":["2024JDRC0034"],"award-info":[{"award-number":["2024JDRC0034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The global spread of COVID-19 led to the rapid authorization of remdesivir as the first antiviral therapy. However, accumulating clinical evidence has linked its use to cardiac adverse effects. Understanding the mechanisms underlying remdesivir-induced cardiotoxicity is critical for optimizing its clinical use and ensuring patient safety. This study investigates the electrophysiological and molecular features underlying remdesivir-induced cardiac toxicity in male and female guinea pigs, aiming to elucidate the sex-dependent differences in cardiac dysfunction and the role of mitochondria in mediating these effects. A cardiac injury model was established via intraperitoneal administration of remdesivir. In vivo telemetry and ex vivo electrocardiography were used for continuous monitoring of cardiac electrical activity, while optical mapping enabled the assessment of action potential parameters and conduction properties. The histopathological alterations and mitochondrial ultrastructure were examined by hematoxylin\u2013eosin staining and transmission electron microscopy. ELISA and Western blot analyses were performed to explore the inflammatory signaling, apoptosis, and mitochondrial dynamics. Remdesivir induced distinct sex-specific patterns of cardiac toxicity. Compared with female guinea pigs, male guinea pigs had significantly more severe myocardial injury, which was characterized by extensive inflammatory cell infiltration, marked mitochondrial disruption, and a higher incidence of sustained ventricular tachyarrhythmia. Overall, remdesivir was associated with sex-dependent cardiac toxicity, accompanied by mitochondrial impairment and inflammatory activation. Male guinea pigs were more susceptible to electrophysiological instability and mitochondrial dysfunction. These findings highlight the importance of carefully evaluating remdesivir\u2019s cardiac effects and support the need for individualized, sex-specific considerations in its clinical administration.<\/jats:p>","DOI":"10.3390\/ijms27083685","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"3685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electrophysiological and Molecular Features of Remdesivir-Induced Cardiac Toxicity in Male and Female Guinea Pigs"],"prefix":"10.3390","volume":"27","author":[{"given":"Chen","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646099, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646099, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646099, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646099, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-5807","authenticated-orcid":false,"given":"Henggui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646099, China"},{"name":"Beijing Academy of Artificial Intelligence, Beijing 100084, China"},{"name":"Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","first-page":"1073","article-title":"The impact of COVID-19 on health and health systems","volume":"31","author":"Haileamlak","year":"2021","journal-title":"Ethiop. 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