title: Influence of the Purkinje-muscle junction on transmural repolarization heterogeneity.
abstract: OBJECTIVE
  To elucidate the properties of the PMJ and myocardium underlying these effects. Transmural heterogeneity of action potential duration (APD) is known to play an important role in arrhythmogenesis. Regions of non-uniformities of APD gradients often overlap considerably with the location of Purkinje-muscle junctions (PMJs). We therefore hypothesized that such junctions are novel sources of local endocardial and transmural heterogeneity of repolarization, and that remodelling due to heart failure modulates this response.
  
  
  RESULTS
  Spatial gradients of endocardial APD in left ventricular wedge preparations from healthy sheep (n = 5) were correlated with locations of PMJs identified through Purkinje stimulation under optical mapping. APD prolongation was dependent on proximity of the PMJ to the imaged surface, whereby shallow PMJs significantly modulated local APD when stimulating either Purkinje (P = 0.0116) or endocardium (P = 0.0123). In addition, we model a PMJ in 5 × 5× 10 mm transmural tissue wedges using healthy and novel failing human ventricular and Purkinje ionic models. Short distances of the PMJ to cut surfaces (<0.875 mm) revealed that APD maxima were localized to the PMJ in healthy myocardium, whereas APD minima were observed in failing myocardium. Amplitudes and spatial gradients of APD were prominent at functional PMJs and quiescent PMJs. Furthermore, increasing the extent of Purkinje fibre branching or decreasing tissue conductivity augmented local APD prolongation in both failing and non-failing models.
  
  
  CONCLUSIONS
  The Purkinje network has the potential to influence myocardial AP morphology and rate-dependent behaviour, and furthermore to underlie enhanced transmural APD heterogeneities and spatial gradients of APD in non-failing and failing myocardium.
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France richard.walton@ihu-liryc.fr richard.walton@u-bordeaux2.fr.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Walton
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France.
authors.forename: Marine E
authors.initials: ME
authors.lastname: Martinez
authors.affiliation: Biomedical Engineering Department, Division of Imaging Sciences, King's College London, London, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bishop
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France CHU de Bordeaux, Hôpital du Haut lévêque, Pessac, France.
authors.forename: Mélèze
authors.initials: M
authors.lastname: Hocini
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France CHU de Bordeaux, Hôpital du Haut lévêque, Pessac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Haïssaguerre
authors.affiliation: Institute of Biophysics, Medical University of Graz, Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Plank
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, Bordeaux, France Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bernus
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, CRCTB U1045, PTIB - Campus Xavier Arnozan, Avenue du Haut Lévêque, 33600 Bordeaux, France L'Institut de Mathématiques de Bordeaux UMR 5251, Université de Bordeaux, Bordeaux, France Department of Electrical and Computer Engineering, University of Calgary, Calgary, Canada.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Vigmond
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004699:Endocardium / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009206:Myocardium / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism*; D012756:Sheep
keywords: Conduction system; Optical mapping; Purkinje-muscle junction; Repolarization; Transmural heterogeneity