A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury

A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury Steven Moran, Omar Selim, Aida Sarcon, Mehmet Furkan Tunaboylu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5582098/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Sep, 2025 Read the published version in Lab Animal → Version 1 posted You are reading this latest preprint version Abstract Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- & limb- threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. To date, studies that evaluated reperfusion injury-induced neuromuscular impairment rely on terminal ex vivo procedures and do not provide clinically translatable measurements. Furthermore, it is unclear if upper extremity musculature exhibits a different ischemic threshold compared to the lower limb given the relatively rare incidence of upper limb ischemia. Here, we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper extremity reperfusion injury and allows for monitoring in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS provided insights on gross motor and electrophysiological alterations upper extremity reperfusion injury. We identify gait coordination parameters such as stride frequency and forelimb-hindlimb coordination index and electrophysiological metrics including compound muscle action potential amplitude as objective, non-invasive outcome measures for limb function assessment in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction. Health sciences/Medical research/Preclinical research Health sciences/Medical research/Experimental models of disease Postreperfusion syndrome forelimb ischemia preclinical model rhabdomyolysis skeletal muscle reperfusion Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 24 Sep, 2025 Read the published version in Lab Animal → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5582098","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":408273526,"identity":"277e1b8d-b1b8-44e9-8f84-994bea77bad1","order_by":0,"name":"Steven Moran","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYNCDD1BaghjFYEWMM0jWwsxDjBbd9t6HnwsY6ur4JZKPPbbNsUvsZ2A+eJsHjxazM8eNpWcwHJaQnJGWbpy7LTlxZgNbsjVeLTfSGKR5GA5IGJw5Yyadu405ccMBHjNpAlqYf/Mw1EnYnzn/TdpyWz1QC/83QlrYgAqYJQzYe9ikGbcdBtnChl/LmWNs1jwGhyVnHG8zk+zddtx4ZjObseUcfFqOtzHf5qmo4+dvZn4m8XNbtWw/e/PDG2/waIEAAwTTsYGZoHI0YE+qhlEwCkbBKBj+AAD7CEOlt/550wAAAABJRU5ErkJggg==","orcid":"","institution":"Mayo Clinic","correspondingAuthor":true,"prefix":"","firstName":"Steven","middleName":"","lastName":"Moran","suffix":""},{"id":408273527,"identity":"9d4346d6-6eb4-42e3-a174-1d3c76846053","order_by":1,"name":"Omar Selim","email":"","orcid":"https://orcid.org/0000-0002-4178-2227","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Omar","middleName":"","lastName":"Selim","suffix":""},{"id":408273528,"identity":"475d3cc7-0ed8-45d1-83a4-e2e0501f9074","order_by":2,"name":"Aida Sarcon","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Aida","middleName":"","lastName":"Sarcon","suffix":""},{"id":408273529,"identity":"6ec0db50-d435-451b-9d09-124506244545","order_by":3,"name":"Mehmet Furkan Tunaboylu","email":"","orcid":"https://orcid.org/0009-0004-3859-5166","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Furkan","lastName":"Tunaboylu","suffix":""},{"id":408273530,"identity":"3524b76c-d531-467a-beb6-4186a448f4b3","order_by":4,"name":"Chunfeng Zhao","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Chunfeng","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2024-12-04 19:15:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5582098/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5582098/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41684-025-01601-9","type":"published","date":"2025-09-24T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92146601,"identity":"7679a9e7-74b9-426d-95be-3886bb70e6dc","added_by":"auto","created_at":"2025-09-25 07:11:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3434734,"visible":true,"origin":"","legend":"Article File #1","description":"","filename":"LABANmanuscripttext12425.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5582098/v1_covered_c3fbde3a-d43b-49e4-af89-72493b2e0955.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Postreperfusion syndrome, forelimb ischemia, preclinical model, rhabdomyolysis, skeletal muscle reperfusion","lastPublishedDoi":"10.21203/rs.3.rs-5582098/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5582098/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- \u0026 limb- threatening sequelae. 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