Characterization of electrical activity in post-myocardial infarction scar tissue in rat hearts using multiphoton microscopy.

Ghouri, I. A., Kelly, A., Salerno, S., Garten, K., Stølen, T., Kemi, O.-J. and Smith, G. L. (2018) Characterization of electrical activity in post-myocardial infarction scar tissue in rat hearts using multiphoton microscopy. Frontiers in Physiology, 9, 1454. (doi: 10.3389/fphys.2018.01454) (PMID:30386255) (PMCID:PMC6199960)

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Abstract

Background: The origin of electrical behavior in post-myocardial infarction scar tissue is still under debate. This study aims to examine the extent and nature of the residual electrical activity within a stabilized ventricular infarct scar. Methods and Results: An apical infarct was induced in the left ventricle of Wistar rats by coronary artery occlusion. Five weeks post-procedure, hearts were Langendorff-perfused, and optically mapped using di-4-ANEPPS. Widefield imaging of optical action potentials (APs) on the left ventricular epicardial surface revealed uniform areas of electrical activity in both normal zone (NZ) and infarct border zone (BZ), but only limited areas of low-amplitude signals in the infarct zone (IZ). 2-photon (2P) excitation of di-4-ANEPPS and Fura-2/AM at discrete layers in the NZ revealed APs and Ca2+ transients (CaTs) to 500-600 μm below the epicardial surface. 2P imaging in the BZ revealed superficial connective tissue structures lacking APs or CaTs. At depths greater than approximately 300 μm, myocardial structures were evident that supported normal APs and CaTs. In the IZ, although 2P imaging did not reveal clear myocardial structures, low-amplitude AP signals were recorded at discrete layers. No discernible Ca2+ signals could be detected in the IZ. AP rise times in BZ were slower than NZ (3.50 ± 0.50 ms vs. 2.23 ± 0.28 ms) and further slowed in IZ (9.13 ± 0.56 ms). Widefield measurements of activation delay between NZ and BZ showed negligible difference (3.37 ± 1.55 ms), while delay values in IZ showed large variation (11.88 ± 9.43 ms). Conclusion: These AP measurements indicate that BZ consists of an electrically inert scar above relatively normal myocardium. Discrete areas/layers of IZ displayed entrained APs with altered electrophysiology, but the structure of this tissue remains to be elucidated.

Item Type:Articles
Additional Information:This work was supported by a European Union Framework Programme 7 grant (Grant No. HEALTH-F2-2009-241526) and a British Heart Foundation project grant (Grant No. PG/09/107). AK is funded by a British Heart Foundation project grant (Grant No. PG/17/12/32847). SS is funded by the Norwegian Council for Cardiac Research.
Keywords:Intracellular calcium, myocardial infarction, two-photon microscopy, optical mapping, border zone
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Kemi, Dr Ole and Kelly, Dr Allen and Ghouri, Dr Iffath
Authors: Ghouri, I. A., Kelly, A., Salerno, S., Garten, K., Stølen, T., Kemi, O.-J., and Smith, G. L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Frontiers in Physiology
Publisher:Frontiers Media
ISSN:1664-042X
ISSN (Online):1664-042X
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Frontiers in Physiology 9:1454
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
529531Cardiac CaMK in heart failure and exercise trainingOle KemiBritish Heart Foundation (BHF)PG/09/107RI CARDIOVASCULAR & MEDICAL SCIENCES
3003810Investigating the influence of myofibroblast coupling on cardiac conduction and infarct electrophysiologyGodfrey SmithBritish Heart Foundation (BHF)PG/17/12/32847CAMS - Cardiovascular Science