Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling. (May 2016)

• Record Type: Journal Article
• Authors: Nisbet, Ashley M.; Camelliti, Patrizia; Walker, Nicola L.; Burton, Francis L.; Cobbe, Stuart M.; Kohl, Peter; Smith, Godfrey L.
• Is Part Of: Journal of molecular and cellular cardiology. Volume 94(2016:May)
• Page Start: 54
• Page End: 64
• Publication Date: 2016-05
• Subjects: AVN atrio-ventricular node -- AN atrio-nodal -- CHF chronic heart failure -- ERPA atrial effective refractory period -- ERPAVN AVN effective refractory period -- FRPAVN AVN functional refractory period -- LV left ventricle -- LVD left ventricular dysfunction -- MI myocardial infarction -- NH nodo-Hisian -- O/N overnight -- RV right ventricle -- RT room temperature -- Tact activation time; Myocardial infarction -- Heart failure -- Left ventricular dysfunction -- Conduction -- Optical mapping -- Connexins; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.03.011
• Languages: English
• ISSNs: 0022-2828

Abstract

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. Highlights: Chronic myocardial infarction (MI) causes changes in atrio-ventricular node (AVN) function. Isolated hearts post-MI show delays in ventricular activation due to slowed conduction via the AVN. Isolated AVN preparations demonstrated AVN electrical remodelling post-MI. Electrical remodelling is associated with fibrosis and altered expression of connexins in the AVN. AVN dysfunction post-MI is caused by localized functional and structural remodelling.