title: Structural and functional alterations in the atrioventricular node and atrioventricular ring tissue in ischaemia-induced heart failure.
abstract: Heart failure (HF) causes dysfunction of the atrioventricular node (AVN) - first or second-degree heart block is a risk factor for sudden cardiac death in HF patients. The aim of the study was to determine if HF causes remodelling of the AVN and right atrioventricular ring (RAVR). HF was induced in rats (n=4) by ligation of the proximal left coronary artery, which resulted in a large infarct of the left ventricle. Sham-operated rats (n=4) were used as controls. Eight weeks after surgery, functional experiments were performed and the hearts were frozen. The body weight of HF rats was similar to control rats, but the mean heart weight of HF rats was significantly enlarged. In HF rats compared to controls, the left ventricle was dilated, left ventricular end-diastolic pressure elevated (21.0 ± 0.6 and 5.4 ± 0.2 mm Hg), left ventricular ejection fraction reduced (0.2 ± 0.02 and 0.5 ± 0.02) and left ventricular end-systolic pressure reduced (102 ± 4.2 and 127 ± 3.1 mm Hg). In HF rats, the in vivo and in vitro PR intervals were increased (41% and 20%), as was the Wenckebach cycle length, indicative of AVN dysfunction. The collagen content was significantly increased in the AVN and RAVR indicating fibrosis. Immunolabelling of caveolin3 (cell membrane marker) showed that there was hypertrophy in HF (cell diameter was increased by 63%, 39% in AVN, RAVR). The TUNEL assay showed that the myocytes of the AVN and RAVR in HF undergo apoptotic cell death. Immunolabelling showed that expression of HCN4 was significantly decreased in the AVN and RAVR (43% and 47%) in HF. We conclude that in HF there is remodelling of the AVN and RAVR and this remodelling may explain the AVN dysfunction.
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yanni
authors.affiliation: Medical Centre of Postgraduate Education, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Maczewski
authors.affiliation: Medical Centre of Postgraduate Education, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Mackiewicz
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Siew
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK, and National Research Tomsk Polytechnic University and Mental Health Research Institute SB RAMSci, Tomsk, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Fedorenko
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Atkinson
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Price
authors.affiliation: Medical Centre of Postgraduate Education, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Beresewicz
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Anderson
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Boyett
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK. halina.dobrzynski@manchester.ac.uk.
authors.forename: Halina
authors.initials: H
authors.lastname: Dobrzynski
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley