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In an in vitro DMD cardiomyocyte model, nicorandil reversed stress-induced cell injury through multiple pathways implicated in DMD<jats:italic>.<\/jats:italic>We aimed to test the efficacy of nicorandil on the progression of cardiomyopathy in<jats:italic>mdx<\/jats:italic>mice following a 10-day treatment protocol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A subset of<jats:italic>mdx<\/jats:italic>mice was subjected to low-dose isoproterenol injections over 5\u00a0days to induce a cardiac phenotype and treated with vehicle or nicorandil for 10\u00a0days. Baseline and day 10 echocardiograms were obtained to assess cardiac function. At 10\u00a0days, cardiac tissue was harvested for further analysis, which included histologic analysis and assessment of oxidative stress. Paired student\u2019s t test was used for in group comparison, and ANOVA was used for multiple group comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to vehicle treated mice, isoproterenol decreased ejection fraction and fractional shortening on echocardiogram. Nicorandil prevented isoproterenol induced cardiac dysfunction. Isoproterenol increased cardiac fibrosis, which nicorandil prevented. Isoproterenol increased gene expression of NADPH oxidase, which decreased to baseline with nicorandil treatment. Superoxide dismutase 2 protein expression increased in those treated with nicorandil, and xanthine oxidase activity decreased in mice treated with nicorandil during isoproterenol stress compared to all other groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, nicorandil is cardioprotective in<jats:italic>mdx<\/jats:italic>mice and warrants continued investigation as a therapy for DMD associated cardiomyopathy.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12872-021-02112-4","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T13:03:59Z","timestamp":1623762239000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cardioprotective effect of nicorandil on isoproterenol induced cardiomyopathy in the Mdx mouse model"],"prefix":"10.1186","volume":"21","author":[{"given":"Rachel T.","family":"Sullivan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc T.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Haberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"Beatka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Z.","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Strande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"2112_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0960-8966(91)90039-U","volume":"1","author":"AEH Emery","year":"1991","unstructured":"Emery AEH. 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International, national, and\/or institutional guidelines for care and use of laboratory animals were followed. All animal experiments were performed at the Medical College of Wisconsin and were approved by the institutional animal care and use committee (procedure protocol AUA00003547). This study was carried out in compliance with the ARRIVE guidelines. No informed consent was required as no human subject research was conducted.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"302"}}