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Amiodarone, a Vaughan-Williams class III antiarrhythmic drug, has been widely used to treat life-threatening arrhythmia and cardiac arrest worldwide. In addition to its inhibitory effects on the potassium channel, amiodarone also blocks various sodium ion transporters, including the voltage-gated sodium channel, sodium pump, and Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>+<\/jats:sup> exchanger. Considering these pharmacological profile, amiodarone may affect the influx\u2013efflux balance of sodium ion in the hypoxic\u2013ischemic brain. Previous studies suggest that the blockade of the voltage-gated sodium channel during hypoxic\u2013ischemic brain injury exerts neuroprotection. On the contrary, the blockade of sodium pump or Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>+<\/jats:sup> exchanger during hypoxia\u2013ischemia may cause further intracellular sodium accumulation and consequent osmotic cell death. From these perspectives, the effects of amiodarone on sodium ion balance on the hypoxic\u2013ischemic brain can be both protective and detrimental depending on the clinical and pathophysiological conditions. In this study, we therefore investigated the effect of amiodarone on hypoxic\u2013ischemic brain injury using a murine experimental model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with the control group mice, mice that received amiodarone after induction of 40-min hypoxic\u2013ischemic brain injury exhibited lower survival rates over 7\u00a0days and worse neurological function. After 25-min hypoxic\u2013ischemic brain injury, amiodarone treated mice exhibited larger infarct volumes (16.0\u2009\u00b1\u20096.9 vs. 24.2\u2009\u00b1\u20096.8\u00a0mm<jats:sup>3<\/jats:sup>, P\u2009&lt;\u20090.05) and worse neurological function. In addition, the brains harvested from the amiodarone-treated mice contained larger amounts of sodium (194.7\u2009\u00b1\u200945.1 vs. 253.5\u2009\u00b1\u200950.9\u00a0mEq\/kg dry weight, P\u2009&lt;\u20090.01) and water (259.3\u2009\u00b1\u20098.9 vs. 277.2\u2009\u00b1\u200912.5\u00a0mg, P\u2009&lt;\u20090.01). There were no significant differences in hemodynamic parameters between groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Amiodarone exacerbated brain injuries and neurological outcomes after hypoxic\u2013ischemic insults. Severe brain sodium accumulation and brain edema were associated with the detrimental effects of amiodarone. Amiodarone at the clinical dose can exacerbate brain injury after hypoxic\u2013ischemic insult by affecting sodium ion transportation and facilitate intracellular sodium accumulation in the brain.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12868-019-0544-2","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T14:02:22Z","timestamp":1576936942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Amiodarone exacerbates brain injuries after hypoxic\u2013ischemic insult in mice"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9783-2991","authenticated-orcid":false,"given":"Masakazu","family":"Kotoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohei","family":"Hishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiko","family":"Ishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuha","family":"Mitsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"544_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S0006-8993(00)03167-X","volume":"890","author":"Y Aoki","year":"2001","unstructured":"Aoki Y, Tamura M, Itoh Y, Ukai Y. 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The experimental protocol was reviewed and approved by the University of Yamanashi Animal Care Committee.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"62"}}