{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:17:45Z","timestamp":1776309465673,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/11\/69\/29017"],"award-info":[{"award-number":["FS\/11\/69\/29017"]}],"id":[{"id":"10.13039\/501100000274","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\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The Purkinje network is essential for normal electrical impulse propagation in the heart but has also been implicated in ventricular arrhythmias. Previous experimental work has suggested that not all Purkinje-myocardial junctions (PMJs) are active at rest due to source-sink mismatch at the PMJs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We hypothesized that pathological conditions that cause gap junction uncoupling (e.g., acute ischaemia), would increase the number of active PMJs, leading to more complex activation patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated this using a whole-heart intact Purkinje system preparation that allowed direct high-resolution endocardial mapping to interrogate PMJ function. Twelve (7 control, five rotigaptide) Langendorff-perfused hearts from New Zealand white rabbits were subjected to an ischaemia-reperfusion protocol and optically mapped. Computational modelling was performed to determine the effects of gap junction coupling on PMJ function, and on the complexity of endocardial activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During ischaemia, the percentage of right ventricle area activated within the first 5 ms decreased from baseline 62% \u00b1 7% to 52% \u00b1 8% during early ischaemia (p = 0.04), consistent with slowing of conduction. This was followed by a paradoxical increase in late-ischaemia (60% \u00b1 8%) due to extra regions of early activation. Gap junction enhancement with rotigaptide during ischaemia abolished the aforementioned pattern. Parallel computational experiments replicated experimental findings only when the number of functional PMJs was increased during ischaemia. With more active PMJs, there were more breakthrough sites with increased complexity of activation, as also measured in biological preparations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Normally-quiescent PMJs can become active in the context of gap junction uncoupling during acute ischaemia. Pharmacological gap junction modulation may alter propagation patterns across PMJs and may be used as a therapeutic strategy for Purkinje system associated arrhythmias.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2025.1540400","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:26:58Z","timestamp":1746509218000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Acute ischaemia and gap junction modulation modify propagation patterns across Purkinje-myocardial junctions"],"prefix":"10.3389","volume":"16","author":[{"given":"Richard J.","family":"Jabbour","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham","family":"Behradfar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Debney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Nygren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Hartley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Efimov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9l\u00e8ze","family":"Hocini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas S.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu Siong","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Vigmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1161\/01.res.66.1.123","article-title":"Electrical properties of canine subendocardial Purkinje fibers surviving in 1-day-old experimental myocardial infarction","volume":"66","author":"Argentieri","year":"1990","journal-title":"Circulation Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1016\/j.bpj.2010.02.033","article-title":"Ionic mechanisms for electrical heterogeneity between rabbit Purkinje fiber and ventricular cells","volume":"98","author":"Aslanidi","year":"2010","journal-title":"Biophysical J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.cbpa.2006.10.036","article-title":"Activation and repolarization patterns in the ventricular epicardium under sinus rhythm in frog and rabbit hearts","volume":"146","author":"Azarov","year":"2007","journal-title":"Mol. and Integr. physiology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1109\/TMI.2021.3073499","article-title":"Estimation of personalized minimal Purkinje systems from human electro-anatomical maps","volume":"40","author":"Barber","year":"2021","journal-title":"IEEE Trans. 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