Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts
Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether PFs and specifically TRPM4 channels, play a role in these mechanically-induced arrhythmias. Pseudo-ECGs and left ventricular (LV) a...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Physiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665944123000019 |
| _version_ | 1797398972390703104 |
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| author | Miriam Hurley Sarbjot Kaur Richard Walton Amelia Power Michel Haïssaguerre Olivier Bernus Marie-Louise Ward Ed White |
| author_facet | Miriam Hurley Sarbjot Kaur Richard Walton Amelia Power Michel Haïssaguerre Olivier Bernus Marie-Louise Ward Ed White |
| author_sort | Miriam Hurley |
| collection | DOAJ |
| description | Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether PFs and specifically TRPM4 channels, play a role in these mechanically-induced arrhythmias. Pseudo-ECGs and left ventricular (LV) activation, measured by optical mapping, were recorded in isolated, Langendorff-perfused, rat hearts. The LV endocardial surface was irrigated with experimental agents, via an indwelling catheter. The number and period of ectopic activations was measured during LV lumen inflation via an indwelling fluid-filled balloon (100 μL added over 2 s, maintained for 38 s). Mechanically-induced arrhythmias occurred during balloon inflation: they were multifocal, maximal in the first 5 s and ceased within 20 s. Optical mapping revealed activation patterns indicating PF-mediated and ectopic focal sources. Irrigation of the LV lumen with Lugol solution (IK/I2) for 10s reduced ectopics by 93% (n = 16, P < 0.001); with ablation of endocardial PFs confirmed by histology. Five min irrigation of the LV lumen with 50 μM 9-Phenanthrol, a blocker of TRPM4 channels, reduced ectopics by 39% (n = 15, P < 0.01). Immunohistochemistry confirmed that TRPM4 was more abundant in PFs than myocardium. Our results show that the endocardial surface plays an important role in these mechanically-induced ectopic activations. Ectopic activation patterns indicate a participation of PFs in these arrhythmias, with a potential involvement of TRPM4 channels, shown by the reduction of arrhythmias by 9-Phenanthrol. |
| first_indexed | 2024-03-09T01:34:16Z |
| format | Article |
| id | doaj.art-73a17cc8e966401b91bca55c5efa4e90 |
| institution | Directory Open Access Journal |
| issn | 2665-9441 |
| language | English |
| last_indexed | 2024-03-09T01:34:16Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Physiology |
| spelling | doaj.art-73a17cc8e966401b91bca55c5efa4e902023-12-09T06:07:51ZengElsevierCurrent Research in Physiology2665-94412023-01-016100098Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat heartsMiriam Hurley0Sarbjot Kaur1Richard Walton2Amelia Power3Michel Haïssaguerre4Olivier Bernus5Marie-Louise Ward6Ed White7School of Biomedical Sciences, University of Leeds, Leeds, UKDepartment of Physiology, University of Auckland, Auckland, New ZealandUniversité Bordeaux, INSERM Centre de recherche Cardio-Thoracique de Bordeaux, Pessac, Bordeaux, France; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation, Bordeaux Université, Pessac, Bordeaux, FranceDepartment of Physiology, University of Auckland, Auckland, New ZealandUniversité Bordeaux, INSERM Centre de recherche Cardio-Thoracique de Bordeaux, Pessac, Bordeaux, France; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation, Bordeaux Université, Pessac, Bordeaux, France; Bordeaux University Hospital (CHU), Electrophysiology and Ablation Unit, Pessac, FranceUniversité Bordeaux, INSERM Centre de recherche Cardio-Thoracique de Bordeaux, Pessac, Bordeaux, France; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation, Bordeaux Université, Pessac, Bordeaux, FranceDepartment of Physiology, University of Auckland, Auckland, New ZealandSchool of Biomedical Sciences, University of Leeds, Leeds, UK; Corresponding author. Garstang Building, School of Biomedical Sciences, University of Leeds, LS29JT, Leeds, UK.Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether PFs and specifically TRPM4 channels, play a role in these mechanically-induced arrhythmias. Pseudo-ECGs and left ventricular (LV) activation, measured by optical mapping, were recorded in isolated, Langendorff-perfused, rat hearts. The LV endocardial surface was irrigated with experimental agents, via an indwelling catheter. The number and period of ectopic activations was measured during LV lumen inflation via an indwelling fluid-filled balloon (100 μL added over 2 s, maintained for 38 s). Mechanically-induced arrhythmias occurred during balloon inflation: they were multifocal, maximal in the first 5 s and ceased within 20 s. Optical mapping revealed activation patterns indicating PF-mediated and ectopic focal sources. Irrigation of the LV lumen with Lugol solution (IK/I2) for 10s reduced ectopics by 93% (n = 16, P < 0.001); with ablation of endocardial PFs confirmed by histology. Five min irrigation of the LV lumen with 50 μM 9-Phenanthrol, a blocker of TRPM4 channels, reduced ectopics by 39% (n = 15, P < 0.01). Immunohistochemistry confirmed that TRPM4 was more abundant in PFs than myocardium. Our results show that the endocardial surface plays an important role in these mechanically-induced ectopic activations. Ectopic activation patterns indicate a participation of PFs in these arrhythmias, with a potential involvement of TRPM4 channels, shown by the reduction of arrhythmias by 9-Phenanthrol.http://www.sciencedirect.com/science/article/pii/S2665944123000019Ventricular arrhythmiasStretchEndocardiumPurkinje fibresTRPM4 |
| spellingShingle | Miriam Hurley Sarbjot Kaur Richard Walton Amelia Power Michel Haïssaguerre Olivier Bernus Marie-Louise Ward Ed White Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts Current Research in Physiology Ventricular arrhythmias Stretch Endocardium Purkinje fibres TRPM4 |
| title | Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts |
| title_full | Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts |
| title_fullStr | Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts |
| title_full_unstemmed | Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts |
| title_short | Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts |
| title_sort | endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of purkinje fibres in isolated rat hearts |
| topic | Ventricular arrhythmias Stretch Endocardium Purkinje fibres TRPM4 |
| url | http://www.sciencedirect.com/science/article/pii/S2665944123000019 |
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