title: Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.
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) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (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 14ms (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 20ms) 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.
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Nisbet
authors.affiliation: School of Biosciences and Medicine, University of Surrey, Guildford, GU2 7XH, UK. Electronic address: p.camelliti@surrey.ac.uk.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Camelliti
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Walker
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Burton
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Cobbe
authors.affiliation: Institute for Experimental Cardiovascular Medicine, University Heart Centre Freiburg - Bad Krozingen, Medical School of the University of Freiburg, Germany; Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield UB9 6JH, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Kohl
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology*; D001919:Bradycardia / Q000209:etiology* / Q000503:physiopathology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
chemical_list: D017630:Connexins
keywords: Conduction; Connexins; Heart failure; Left ventricular dysfunction; Myocardial infarction; Optical mapping