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Whether SDH inhibition yields protection in diabetic individuals and translates into human cardiac tissue remain unknown. In isolated perfused hearts from 24 weeks old male Zucker diabetic fatty (ZDF) and age matched non-diabetic control rats and atrial trabeculae from patients with and without diabetes, we compared infarct size, contractile force recovery and mitochondrial function. The cardioprotective effect of a 10\u2009minutes DiMAL administration prior to global ischemia and ischemic preconditioning (IPC) was evaluated. In non-diabetic hearts exposed to IR, DiMAL 0.1\u2009mM reduced infarct size compared to IR (55\u2009\u00b1\u20097% vs. 69\u2009\u00b1\u20096%, p\u2009&lt;\u20090.05). Mitochondrial respiration was reduced by DiMAL 0.6\u2009mM compared to sham and DiMAL 0.1\u2009mM (p\u2009&lt;\u20090.05). In diabetic hearts an increased concentration of DiMAL (0.6\u2009mM) was required for protection compared to IR (64\u2009\u00b1\u200913% vs. 79\u2009\u00b1\u20098%, p\u2009&lt;\u20090.05). Mitochondrial function remained unchanged. In trabeculae from humans without diabetes, IPC and DiMAL improved contractile force recovery compared to IR (43\u2009\u00b1\u200912% and 43\u2009\u00b1\u200913% vs. 23\u2009\u00b1\u200913%, p\u2009&lt;\u20090.05) but in patients with diabetes only IPC provided protection compared to IR (51\u2009\u00b1\u200915% vs. 21\u2009\u00b1\u20098%, p\u2009&lt;\u20090.05). Neither IPC nor DiMAL modulated mitochondrial respiration in patients. Cardioprotection by SDH inhibition is possible in human tissue, but depends on diabetes status. The narrow therapeutic range and discrepancy in respiration between experimental and human studies may limit clinical translation.<\/jats:p>","DOI":"10.1038\/s41598-020-67247-4","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:03:02Z","timestamp":1593079382000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Cardioprotective effect of succinate dehydrogenase inhibition in rat hearts and human myocardium with and without diabetes mellitus"],"prefix":"10.1038","volume":"10","author":[{"given":"Nichlas Riise","family":"Jespersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Vognstoft","family":"Hjortbak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Ravn","family":"Lassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaj Brejnholt","family":"St\u00f8ttrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Johnsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille Tilma","family":"Tonnesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Henrik","family":"Kimose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Erik","family":"B\u00f8tker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"67247_CR1","doi-asserted-by":"publisher","first-page":"H1225","DOI":"10.1152\/ajpheart.00027.2018","volume":"314","author":"HE Botker","year":"2018","unstructured":"Botker, H. 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