{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:12:31Z","timestamp":1753884751939,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R56HL160835\u201001"],"award-info":[{"award-number":["1R56HL160835\u201001"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia\u2010induced fatal cardiac arrhythmias. To test this hypothesis, adult, non\u2010diabetic Sprague\u2013Dawley rats were subjected to hyperinsulinemic\u2010severe hypoglycemic clamps (3\u2009h, 10\u201315\u2009mg\/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (<jats:italic>n<\/jats:italic>\u2009=\u200926) or artificial cerebrospinal fluid (aCSF) (<jats:italic>n<\/jats:italic>\u2009=\u200920) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (<jats:italic>n<\/jats:italic>\u2009=\u200920) or control (<jats:italic>n<\/jats:italic>\u2009=\u200929). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5\u2010fold increase in third\u2010degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third\u2010degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia.<\/jats:p>","DOI":"10.14814\/phy2.70010","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T04:38:54Z","timestamp":1724474334000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Norepinephrine mediates heart block during severe hypoglycemia in male rats"],"prefix":"10.14814","volume":"12","author":[{"given":"Emily H.","family":"Nuibe","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew E.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-1212","authenticated-orcid":false,"given":"Candace M.","family":"Reno\u2010Bernstein","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.03.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000166876.41694.CA"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2016.00025"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02717"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/1801200a0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v7.i4.204"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.126391"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1987.tb27201.x"},{"volume-title":"Physiology, noradrenergic synapse","year":"2024","author":"Hussain L. 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