title: Architectural correlates of myocardial conduction: changes to the topography of cellular coupling, intracellular conductance, and action potential propagation with hypertrophy in Guinea-pig ventricular myocardium.
abstract: BACKGROUND
  We tested the hypothesis that alterations to action potential conduction velocity (CV) and conduction anisotropy in left ventricular hypertrophy are associated with topographical changes to gap-junction coupling and intracellular conductance by measuring these variables in the same preparations.
  
  
  RESULTS
  Left ventricular papillary muscles were excised from aortic-banded or sham-operated guinea-pig hearts. With intracellular stimulating and recording microelectrodes, CV was measured in 3 dimensions with simultaneous conductance mapping with subthreshold stimuli and correlated with quantitative histomorphometry of myocardial architecture and connexin 43 distribution. In hypertrophied myocardium, CV in the longitudinal axis was smaller and transverse velocity was greater compared with control; associated with similar differences of intracellular conductance, consistent with more cell contacts per cell (5.7 ± 0.2 versus 8.1 ± 0.5; control versus hypertrophy), and more intercalated disks mediating side-to-side coupling (8.2 ± 0.2 versus 10.2 ± 0.4 per cell). Intercalated disk morphology and connexin 43 immunolabelling were not different in hypertrophy. Hypertrophied preparations showed local submillimeter (≈250 μm) regions with slow conduction and low intracellular conductance, which, although not affecting CV on the millimeter scale, were consistent with discontinuities from increased microscopical connective tissue content.
  
  
  CONCLUSIONS
  With myocardial hypertrophy, altered longitudinal and transverse CV, and greater nonuniformity of CV anisotropy correspond to changes of intracellular conductance. These are associated with alteration of myocardial architecture, specifically the topography of cell-cell coupling and gap-junction connectivity.
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.). chris.fry@bristol.ac.uk.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Fry
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Rosaire P
authors.initials: RP
authors.lastname: Gray
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Paramdeep S
authors.initials: PS
authors.lastname: Dhillon
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Rita I
authors.initials: RI
authors.lastname: Jabr
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dupont
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Pravina M
authors.initials: PM
authors.lastname: Patel
authors.affiliation: From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Peters
mesh_terms: D000200:Action Potentials; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D056966:Excitation Contraction Coupling; D006168:Guinea Pigs; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein
keywords: action potentials; connexin 43; gap junctions; left ventricular hypertrophy; slowed conduction velocity