{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:19:42Z","timestamp":1783030782712,"version":"3.54.6"},"reference-count":70,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL163977"],"award-info":[{"award-number":["R01 HL163977"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IIS\u20102406028"],"award-info":[{"award-number":["IIS\u20102406028"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The heart functions within a complex system that adapts its function to alterations in loading via several mechanisms. For example, the baroreflex is a feedback loop that modulates the heart's function on a beat\u2010to\u2010beat basis to control arterial pressure. On the other hand, cardiac growth is an adaptive process that occurs over weeks or months in response to changes in left ventricular loading. In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in simulations of valve disease. To achieve this, we integrated the effects of a baroreflex feedback loop and a growth algorithm into a beating multiscale finite element model of the left ventricle. Our integrated model replicated clinical measures of left ventricular growth in two types of valvular diseases \u2013 aortic stenosis and mitral regurgitation \u2013 at two different levels of severity for each case. Furthermore, our results showed that incorporating the effects of baroreflex control in simulations of left ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth. Finally, our results suggest that the regulation of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered loading due to aortic stenosis and mitral regurgitation.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70077-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The heart adapts its function in response to alterations in loading via short\u2010term and long\u2010term mechanisms.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These mechanisms are essential for maintaining proper blood pressure in the vasculature (baroreflex) and homeostasis in the heart (ventricular growth).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in finite element simulations of valve disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We showed that incorporating the effects of baroreflex control and ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Our results suggest that the regulation of Ca\n                            <jats:sup>2<\/jats:sup>\n                            \u207a dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered ventricular loading.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp288649","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:00:33Z","timestamp":1757696433000},"page":"5535-5560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of baroreflex feedback loop in predictions of left ventricular growth: A multiscale finite element modelling study"],"prefix":"10.1113","volume":"604","author":[{"given":"Hossein","family":"Sharifi","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Mehri","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Department of Physiology University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lik Chuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-9914","authenticated-orcid":false,"given":"Jonathan F.","family":"Wenk","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering University of Kentucky  Lexington KY USA"},{"name":"Department of Surgery University of Kentucky  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"al RJe. (2021).pandas\u2010dev\/pandas: Pandas 1.3.2."},{"key":"e_1_2_6_3_1","article-title":"The FEniCS project version 1.5","volume":"3","author":"Alnaes M. S.","year":"2015","journal-title":"Archive of Numerical Software"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48670-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2018-000919"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.113.000515"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-012-0593-5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.2-208.v1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-36519-5"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201311078"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.07.006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01345.2005"},{"issue":"11","key":"e_1_2_6_13_1","first-page":"1320","article-title":"Myocardial fibrosis and cardiac decompensation in aortic stenosis","volume":"10","author":"Chin C. W. L.","year":"2017","journal-title":"Journal of the American College of Cardiology: Cardiovascular Imaging"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.04.021"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.11.166"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2008.0274"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.114.002397"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.117.007451"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.11.032"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-023-01747-w"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/math9111247"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP285022"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.2894084"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10441-010-9098-5"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00049.2009"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00104.2024"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv680"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mechrescom.2011.11.004"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspa.2015.0641"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"issue":"12","key":"e_1_2_6_31_1","first-page":"2561","article-title":"Diffuse myocardial fibrosis and diastolic function in aortic stenosis","volume":"13","author":"Lee H. J.","year":"2020","journal-title":"Journal of the American College of Cardiology: Cardiovascular Imaging"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-014-0598-0"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-015-0723-8"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.14141120"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-020-00674-4"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.07.736"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2014"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.883587"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/10976640600572889"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2024.09.049"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11340-020-00643-z"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017888"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0007-y"},{"key":"e_1_2_6_44_1","first-page":"e72","article-title":"2020 ACC\/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"143","author":"Otto C. M.","year":"2021","journal-title":"Circulation"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-017-0327-9"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-018-1098-4"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.03.041"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-019-01209-2"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-020-01327-2"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.073239"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2018.11.013"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2023.107690"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-021-00826-5"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-022-01628-8"},{"key":"e_1_2_6_55_1","unstructured":"Sharifi H. Mehri M. Campbell K. S. Lee L. C. &Wenk J. F.(2025).https:\/\/doi.org\/10.5281\/zenodo.16746918."},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-024-03497-x"},{"issue":"1","key":"e_1_2_6_57_1","first-page":"96","article-title":"Symptom onset in aortic stenosis: Relation to sex differences in left ventricular remodeling","volume":"12","author":"Singh A.","year":"2019","journal-title":"Journal of the American College of Cardiolog: Cardiovascular Imaging"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1148\/ryct.2019190027"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2011.09.022"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2004.027441"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/10255842.2023.2222203"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-12-32"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.5.H1733"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1109\/MCSE.2011.37"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.11.004"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0686-2"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53491-0.00008-0"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.4043867"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00177.2016"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.04.016"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-019-01271-w"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288649","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP288649","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T21:32:20Z","timestamp":1783027940000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP288649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":70,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1113\/JP288649"],"URL":"https:\/\/doi.org\/10.1113\/jp288649","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"assertion":[{"value":"2025-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}