{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:37:13Z","timestamp":1776922633256,"version":"3.51.2"},"reference-count":56,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Hypertensive heart disease (HHD) increases risk of ventricular tachycardia (VT) and ventricular fibrillation (VF). The roles of structural <jats:italic>vs<\/jats:italic>. electrophysiological remodelling and age <jats:italic>vs<\/jats:italic>. disease progression are not fully understood. This cross\u2010sectional study of cardiac alterations through HHD investigates mechanistic contributions to VT\/VF risk. Risk was electrically assessed in Langendorff\u2010perfused, spontaneously hypertensive rat hearts at 6, 12 and 18\u00a0months, and paced optical membrane voltage maps were acquired from the left ventricular (LV) free wall epicardium. Distributions of LV patchy fibrosis and 3D cellular architecture in representative anterior LV mid\u2010wall regions were quantified from macroscopic and microscopic fluorescence images of optically cleared tissue. Imaging showed increased fibrosis from 6\u00a0months, particularly in the inner LV free wall. Myocyte cross\u2010section increased at 12\u00a0months, while inter\u2010myocyte connections reduced markedly with fibrosis. Conduction velocity decreased from 12\u00a0months, especially transverse to the myofibre direction, with rate\u2010dependent anisotropy at 12 and 18\u00a0months, but not earlier. Action potential duration (APD) increased when clustered by age, as did APD dispersion at 12 and 18\u00a0months. Among 10 structural, functional and age variables, the most reliably linked were VT\/VF risk, general LV fibrosis, a measure quantifying patchy fibrosis, and non\u2010age clustered APD dispersion. VT\/VF risk related to a quantified measure of patchy fibrosis, but age did not factor strongly. The findings are consistent with the notion that VT\/VF risk is associated with rate\u2010dependent repolarization heterogeneity caused by structural remodelling and reduced lateral electrical coupling between LV myocytes, providing a substrate for heterogeneous intramural activation as HHD progresses.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15231-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>There is heightened arrhythmic risk with progression of hypertensive heart disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Risk is related to increasing left ventricular fibrosis, but the nature of this relationship has not been quantified.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study is a novel systematic characterization of changes in active electrical properties and fibrotic remodelling during progression of hypertensive heart disease in a well\u2010established animal disease model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Arrhythmic risk is predicted by several left ventricular measures, in particular fibrosis quantity and structure, and epicardial action potential duration dispersion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Age alone is not a good predictor of risk.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An improved understanding of links between arrhythmic risk and fibrotic architectures in progressive hypertensive heart disease aids better interpretation of late gadolinium\u2010enhanced cardiac magnetic resonance imaging and electrical mapping signals.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282526","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T17:39:35Z","timestamp":1660930775000},"page":"4119-4135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multimodal imaging shows fibrosis architecture and action potential dispersion are predictors of arrhythmic risk in spontaneous hypertensive rats"],"prefix":"10.1113","volume":"600","author":[{"given":"Prashanna","family":"Khwaounjoo","sequence":"first","affiliation":[{"name":"Auckland Bioengineering Institute University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-2099","authenticated-orcid":false,"given":"Gregory B.","family":"Sands","sequence":"additional","affiliation":[{"name":"Auckland Bioengineering Institute University of Auckland  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