Compliance-Mediated Pressure-Independent Cerebrovascular Regulation: A Distinct Novel Mechanism in Youth

Compliance-Mediated Pressure-Independent Cerebrovascular Regulation: A Distinct Novel Mechanism in Youth | 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 Research Article Compliance-Mediated Pressure-Independent Cerebrovascular Regulation: A Distinct Novel Mechanism in Youth Zijie Wang, Youjun Liu, Hao Sun, Tengfei Li, Liyuan Zhang, Guangfei Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7637429/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Mar, 2026 Read the published version in BioMedical Engineering OnLine → Version 1 posted 12 You are reading this latest preprint version Abstract Cerebral blood flow (CBF) regulation is essential for maintaining brain stability. Most previous studies have focused on middle-aged and elderly populations, where regulation depends on vasodilation with reduced resistance and elevated blood pressure—the Pressure-Dependent mechanism. Whether this paradigm applies to younger individuals remains unclear. Given the rising prevalence of cardiovascular and cerebrovascular risks in young adults, elucidating youth-specific mechanisms is of great importance. In this study, standardized breath-holding was used to induce hypercapnia in 52 young volunteers (23.67 ± 1.77 years). Hemodynamic parameters of both middle cerebral arteries (blood pressure, heart rate, and flow velocity) were measured at rest and during hypercapnia. The breath-holding index (BHI) was calculated, and a hemodynamic model was applied to derive resistance variation ( \(\:{R}_{v}\) ), diameter variation ( \(\:{D}_{v}\) ), and compliance ( \(\:C\) ), forming a multiparametric framework. In total, 104 unilateral datasets underwent multilevel statistical analysis. Two regulatory patterns were identified: Pressure-Dependent (n = 72) and Pressure-Independent (n = 32). The Pressure-Independent group showed greater dilation ( \(\:{D}_{v}\) : 1.4222 vs. 1.2817, P < 0.05) and more stable blood pressure (1.4271 vs. 5.3937 mmHg, P 0.05) via enhanced compliance. Strong correlations were observed between rest and task states for blood pressure, heart rate, and flow velocity (all R > 0.85, P < 0.001). The proposed Pressure-Independent mechanism challenges the conventional paradigm, highlights individual variability, and offers new insights into CBF regulation under hypercapnia. These findings have implications for early diagnosis and personalized interventions in cerebrovascular disorders. cerebral blood flow regulation breath-holding experiment hypercapnia breath-holding index (BHI) cerebrovascular compliance Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Mar, 2026 Read the published version in BioMedical Engineering OnLine → Version 1 posted Editorial decision: Revision requested 14 Feb, 2026 Reviews received at journal 27 Jan, 2026 Reviewers agreed at journal 15 Jan, 2026 Reviewers agreed at journal 07 Jan, 2026 Reviewers agreed at journal 24 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers agreed at journal 17 Oct, 2025 Reviewers invited by journal 06 Oct, 2025 Editor assigned by journal 22 Sep, 2025 Submission checks completed at journal 22 Sep, 2025 First submitted to journal 17 Sep, 2025 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7637429","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":530851570,"identity":"1e30f1b3-1355-4c2d-9f31-3c7b3d4d88a8","order_by":0,"name":"Zijie Wang","email":"","orcid":"","institution":"Beijing University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Zijie","middleName":"","lastName":"Wang","suffix":""},{"id":530851572,"identity":"5b6802a7-eedb-47c2-86db-5ceb32972a45","order_by":1,"name":"Youjun Liu","email":"","orcid":"","institution":"Beijing University of 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Youth","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"biomedical-engineering-online","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmeo","sideBox":"Learn more about [BioMedical Engineering OnLine](http://biomedical-engineering-online.biomedcentral.com/)","snPcode":"12938","submissionUrl":"https://submission.nature.com/new-submission/12938/3","title":"BioMedical Engineering OnLine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cerebral blood flow regulation, breath-holding experiment, hypercapnia, breath-holding index (BHI), cerebrovascular compliance","lastPublishedDoi":"10.21203/rs.3.rs-7637429/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7637429/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCerebral blood flow (CBF) regulation is essential for maintaining brain stability. Most previous studies have focused on middle-aged and elderly populations, where regulation depends on vasodilation with reduced resistance and elevated blood pressure\u0026mdash;the Pressure-Dependent mechanism. Whether this paradigm applies to younger individuals remains unclear. Given the rising prevalence of cardiovascular and cerebrovascular risks in young adults, elucidating youth-specific mechanisms is of great importance.\u003c/p\u003e\u003cp\u003eIn this study, standardized breath-holding was used to induce hypercapnia in 52 young volunteers (23.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77 years). Hemodynamic parameters of both middle cerebral arteries (blood pressure, heart rate, and flow velocity) were measured at rest and during hypercapnia. The breath-holding index (BHI) was calculated, and a hemodynamic model was applied to derive resistance variation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{v}\\)\u003c/span\u003e\u003c/span\u003e), diameter variation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{D}_{v}\\)\u003c/span\u003e\u003c/span\u003e), and compliance (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:C\\)\u003c/span\u003e\u003c/span\u003e), forming a multiparametric framework. In total, 104 unilateral datasets underwent multilevel statistical analysis.\u003c/p\u003e\u003cp\u003eTwo regulatory patterns were identified: Pressure-Dependent (n\u0026thinsp;=\u0026thinsp;72) and Pressure-Independent (n\u0026thinsp;=\u0026thinsp;32). The Pressure-Independent group showed greater dilation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{D}_{v}\\)\u003c/span\u003e\u003c/span\u003e: 1.4222 vs. 1.2817, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and more stable blood pressure (1.4271 vs. 5.3937 mmHg, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), achieving comparable CBF regulation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:BHI\\)\u003c/span\u003e\u003c/span\u003e: 1.3327 vs. 1.3907, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) via enhanced compliance. Strong correlations were observed between rest and task states for blood pressure, heart rate, and flow velocity (all R\u0026thinsp;\u0026gt;\u0026thinsp;0.85, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eThe proposed Pressure-Independent mechanism challenges the conventional paradigm, highlights individual variability, and offers new insights into CBF regulation under hypercapnia. These findings have implications for early diagnosis and personalized interventions in cerebrovascular disorders.\u003c/p\u003e","manuscriptTitle":"Compliance-Mediated Pressure-Independent Cerebrovascular Regulation: A Distinct Novel Mechanism in Youth","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 03:21:37","doi":"10.21203/rs.3.rs-7637429/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-14T10:29:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-27T22:07:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72210766068233700994275880460720731950","date":"2026-01-15T23:47:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115732821309374635433381151017248398807","date":"2026-01-07T15:47:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99440105551688845253578363380442454805","date":"2025-11-24T12:01:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T18:10:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172092310592548919757104021303986585762","date":"2025-10-22T17:13:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217604544617335163308928429126301826980","date":"2025-10-17T13:22:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-06T20:03:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-22T13:45:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-22T13:45:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BioMedical Engineering OnLine","date":"2025-09-17T07:56:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biomedical-engineering-online","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmeo","sideBox":"Learn more about [BioMedical Engineering OnLine](http://biomedical-engineering-online.biomedcentral.com/)","snPcode":"12938","submissionUrl":"https://submission.nature.com/new-submission/12938/3","title":"BioMedical Engineering OnLine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1095d989-6f61-4e2c-b214-2c655b08a035","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:07:18+00:00","versionOfRecord":{"articleIdentity":"rs-7637429","link":"https://doi.org/10.1186/s12938-026-01551-4","journal":{"identity":"biomedical-engineering-online","isVorOnly":false,"title":"BioMedical Engineering OnLine"},"publishedOn":"2026-03-22 15:59:37","publishedOnDateReadable":"March 22nd, 2026"},"versionCreatedAt":"2025-10-17 03:21:37","video":"","vorDoi":"10.1186/s12938-026-01551-4","vorDoiUrl":"https://doi.org/10.1186/s12938-026-01551-4","workflowStages":[]},"version":"v1","identity":"rs-7637429","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7637429","identity":"rs-7637429","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}