94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Physiol.
Sec. Cardiac Electrophysiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1540400
This article is part of the Research TopicAdvancing Our Understanding of the Cardiac Conduction System to Prevent ArrhythmiasView all articles
Acute ischaemia and gap junction modulation modify propagation patterns across Purkinje-myocardial junctions
Provisionally accepted
Richard J Jabbour1
Elham Behradfar2Michael Debney1Anders Nygren2
Adam Hartley1
Igor R Efimov3
Mélèze Hocini4
Nicholas Peters1
Fu Siong Ng1
Edward Joseph Vigmond5,6*- 1Heart Science, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, England, United Kingdom
- 2University of Calgary, Calgary, Alberta, Canada
- 3Northwestern University, Evanston, Illinois, United States
- 4Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France
- 5Lab IMB, Université de Bordeaux, Bordeaux, France
- 6IHU Liryc, Fondation Bordeaux Université, Bordeaux, Aquitaine, France
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.Objective: 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.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, 5 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.Results: During ischaemia, the percentage of right ventricle area activated within the first 5 ms decreased from baseline 62±7% to 52±8% during early ischaemia (p=0.04), consistent with slowing of conduction. This was followed by a paradoxical increase in late-ischaemia (60±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.Normally-quiescent PMJs can become active in the context of gap junction uncoupling during acute ischaemia. Pharmacological gap junction modulation may alter
Keywords: purkinje system, Purkinje-myocardial junction, ischaemia, Computer modelling, Cardiac Electrophysiology
Received: 05 Dec 2024; Accepted: 10 Apr 2025.
Copyright: © 2025 Jabbour, Behradfar, Debney, Nygren, Hartley, Efimov, Hocini, Peters, Ng and Vigmond. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Edward Joseph Vigmond, Lab IMB, Université de Bordeaux, Bordeaux, 33600, France
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.