{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T22:46:15Z","timestamp":1782600375941,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Erlangen Graduate School in Advanced Optical Technologies"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Levosimendan\u2019s calcium sensitizing effects in heart muscle cells are well established; yet, its potential impact on skeletal muscle cells has not been evidently determined. Despite controversial results, levosimendan is still expected to interact with skeletal muscle through off-target sites (further than troponin C). Adding to this debate, we investigated levosimendan\u2019s acute impact on fast-twitch skeletal muscle biomechanics in a length-dependent activation study by submersing single muscle fibres in a levosimendan-supplemented solution. We employed our MyoRobot technology to investigate the calcium sensitivity of skinned single muscle fibres alongside their stress\u2013strain response in the presence or absence of levosimendan (100 \u00b5M). While control data are in agreement with the theory of length-dependent activation, levosimendan appears to shift the onset of the \u2018descending limb\u2019 of active force generation to longer sarcomere lengths without notably improving myofibrillar calcium sensitivity. Passive stretches in the presence of levosimendan yielded over twice the amount of enlarged restoration stress and Young\u2019s modulus in comparison to control single fibres. Both effects have not been described before and may point towards potential off-target sites of levosimendan.<\/jats:p>","DOI":"10.3390\/ijms25116191","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T11:48:50Z","timestamp":1717501730000},"page":"6191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Levosimendan\u2019s Effects on Length-Dependent Activation in Murine Fast-Twitch Skeletal Muscle"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-2593","authenticated-orcid":false,"given":"Michael","family":"Haug","sequence":"first","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"},{"name":"Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan-Str. 6, 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4805-0333","authenticated-orcid":false,"given":"Mena","family":"Michael","sequence":"additional","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"},{"name":"Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan-Str. 6, 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9227-8031","authenticated-orcid":false,"given":"Paul","family":"Ritter","sequence":"additional","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"},{"name":"Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan-Str. 6, 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Kovbasyuk","sequence":"additional","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eleni","family":"Vazakidou","sequence":"additional","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-2049","authenticated-orcid":false,"given":"Oliver","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan Str. 3, 91052 Erlangen, Germany"},{"name":"Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Paul-Gordan-Str. 6, 91052 Erlangen, Germany"},{"name":"School of Biomedical Sciences, University of New South Wales, Wallace Wurth Building, 18 High St., Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0140-6736(02)09455-2","article-title":"Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): A randomised double-blind trial","volume":"360","author":"Follath","year":"2002","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/14779072.2021.1905520","article-title":"An update on levosimendan in acute cardiac care: Applications and recommendations for optimal efficacy and safety","volume":"19","author":"Heringlake","year":"2021","journal-title":"Expert Rev. 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