{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:21:52Z","timestamp":1773368512271,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM148716"],"award-info":[{"award-number":["R01GM148716"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>General anesthetics can adversely affect the heart, negatively impacting chronotropy, electrical conduction, and myocardial contractility. The intravenous sedative\u2010hypnotic, propofol, for example, impairs ventricular contraction at clinically relevant doses and can cause dysrhythmias and atrioventricular block with acute administration. In addition, high cumulative propofol doses can induce bradyarrhythmias, cardiac conduction abnormalities, and myocardial failure. As with propofol, the recently identified intravenous anesthetic agent, ubiquinone\u20105 (Ub5), causes bradycardia and complete heart block at supratherapeutic doses. However, the cardiac effects of clinically relevant Ub5 doses are unknown. Thus, we aimed to determine how therapeutic doses of Ub5 impact cardiac rhythm, hypothesizing that Ub5 would interfere with dromotropy. We tested our hypothesis in\u00a0vivo in the young adult mouse and ex\u00a0vivo in the isolated\u2010perfused murine heart. We then determined mechanistic contributors of Ub5\u2010induced cardiotoxicity in isolated cardiomyocyte mitochondria. We found that Ub5 caused type 1\u2009s\u2010degree heart block and compromised the mitochondrial membrane potential in isolated cardiomyocyte mitochondria by inhibiting electron transport and inducing excessive proton leak. Pharmacological inhibition of the aspartate\u2013glutamate carrier, Aralar, rescued Ub5\u2010mediated disturbances in cardiac rhythm in the isolated\u2010perfused heart. The findings suggest that Ub5 can impact cardiac conduction in a targetable manner, carrying importance for future drug development efforts.<\/jats:p>","DOI":"10.1096\/fj.202504065rr","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:27:41Z","timestamp":1771237661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targetable Effects of the Anesthetic, Ubiquinone\u20105, on Murine Cardiac Rhythm"],"prefix":"10.1096","volume":"40","author":[{"given":"Haeun","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Columbia University Irving Medical Center  New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Columbia University Irving Medical Center  New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe","family":"Shi","sequence":"additional","affiliation":[{"name":"University of Missouri\u2010Kansas City School of Medicine  Kansas City Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3406-5836","authenticated-orcid":false,"given":"Richard J.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Columbia University Irving Medical Center  New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.09.071"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2019.05.001"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539\u2010199204000\u201000015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000003757"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199201000\u201000018"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010200010000\u201000027"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.259556"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13302"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199508000\u201000019"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/62.2.213"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-198910000-00019"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.12.025"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.305.6854.613"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460\u20109592.1998.00282.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010022\u201001985\u20101"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15402"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000484"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1996.0280t.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001503\u2010200206000\u201000010"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005549"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202301280R"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.02.018"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107955200"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000283RR"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505286200"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000905"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2017.07.009"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.203"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11897\u2010023\u201000592\u20103"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102017\u2010104891"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/pace.14607"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab426"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.954"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202504065RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202504065RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202504065RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:40:45Z","timestamp":1773326445000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202504065RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,16]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2,28]]}},"alternative-id":["10.1096\/fj.202504065RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202504065rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,16]]},"assertion":[{"value":"2025-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71598"}}