{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:45:13Z","timestamp":1789911913361,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004765","name":"Honeywell Hometown Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01 HL133360"],"award-info":[{"award-number":["U01 HL133360"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL161696"],"award-info":[{"award-number":["R01 HL161696"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["OT2 OD030534"],"award-info":[{"award-number":["OT2 OD030534"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1940700"],"award-info":[{"award-number":["1940700"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OAC\u20101919839"],"award-info":[{"award-number":["OAC\u20101919839"]}],"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":[[2025,3]]},"abstract":"\n Abstract<\/jats:title>\n \n Loss of cardiac physiological function following myocardial infarction (MI) is accompanied by neural adaptations in the baroreflex that are compensatory in the short term, but then become associated with long\u2010term disease progression. One marker of these adaptations is decreased baroreflex sensitivity, a strong predictor of post\u2010MI mortality. The relative contributions of cardiac remodelling and neural adaptation in the sensory, central brainstem and peripheral ganglionic loci to baroreflex sensitivity changes remain underexplored. We used a computational model\u2010based approach that accounts for the short\u2010term dynamics of closed\u2010loop human cardiac control to integrate disparate experimental studies on neural adaptation following MI into a unified quantitative framework. We developed an ensemble of 59 distinct model parameterizations that account for the clinically observed heterogeneity of cardiac control in healthy individuals. We simulated an\n in silico<\/jats:italic>\n cohort of 35,400 patients with MI, corresponding to six scenarios of one or more loci of neural adaptation coupled with cardiac remodelling. We evaluated the range of MI\u2010induced shifts in arterial pressure, heart rate and baroreflex curve responses. Our results show that adaptation in any single neural locus coupled with cardiac remodelling is sufficient to account for the MI\u2010induced haemodynamic and autonomic changes observed experimentally. Of the adaptation pathways, we found that individuals with central or peripheral vagal efferent adaptation and preserved baroreceptor gain could maintain high baroreflex sensitivity after ischaemic injury. These results suggest that there are a multitude of adaptive pathways for tuning the baroreflex circuit to shift cardiac control physiology, potentially explaining patient heterogeneity post\u2010MI.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Baroreflex sensitivity is a strong indicator of post\u2010myocardial ischaemia survival and is variable among individuals.<\/jats:p>\n <\/jats:list-item>\n \n \n We fine\u2010tuned a computational model ensemble based on physiological observations to develop an\n in silico<\/jats:italic>\n patient cohort consistent with the range of baroreflex responses observed experimentally.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Simulation and analysis of the\n in silico<\/jats:italic>\n cohort show that individuals with a functional afferent pathway and the ability to adapt along the vagal efferent pathway can maintain baroreflex sensitivity post\u2010cardiac ischaemia.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp287596","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T02:45:43Z","timestamp":1735181143000},"page":"2021-2042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Computational modelling of cardiac control following myocardial infarction using an\n in silico<\/i>\n patient cohort"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-5711","authenticated-orcid":false,"given":"Michelle M.","family":"Gee","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of Delaware Newark DE USA"},{"name":"Daniel Baugh Institute for Functional Genomics and Computational Biology Department of Pathology and Genomic Medicine Thomas Jefferson University Philadelphia PA 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