Nisbet, A. M., Camelliti, P., Walker, N. L., Burton, F. L., Cobbe, S. M., Kohl, P. and Smith, G. L. (2016) Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: role of fibrosis and connexin remodelling. Journal of Molecular and Cellular Cardiology, 94, pp. 54-64. (doi: 10.1016/j.yjmcc.2016.03.011) (PMID:27021518) (PMCID:PMC4873602)
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Abstract
Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8 weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7 ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14 ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20 ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte–non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN.
| Item Type: | Articles |
|---|---|
| Additional Information: | Financially supported by the British Heart Foundation (FS/05/010/18435 and FS/02/018/13463) and the European Research Council (AdG CardioNECT). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Smith, Professor Godfrey and Burton, Dr Francis and Cobbe, Professor Stuart |
| Authors: | Nisbet, A. M., Camelliti, P., Walker, N. L., Burton, F. L., Cobbe, S. M., Kohl, P., and Smith, G. L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of Molecular and Cellular Cardiology |
| Publisher: | Elsevier |
| ISSN: | 0022-2828 |
| ISSN (Online): | 1095-8584 |
| Published Online: | 25 March 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Journal of Molecular and Cellular Cardiology 94:54-64 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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