title: Subepicardial action potential characteristics are a function of depth and activation sequence in isolated rabbit hearts.
abstract: BACKGROUND
  Electric excitability in the ventricular wall is influenced by cellular electrophysiology and passive electric properties of the myocardium. Action potential (AP) rise time, an indicator of myocardial excitability, is influenced by conduction pattern and distance from the epicardial surface. This study examined AP rise times and conduction velocity as the depolarizing wavefront approaches the epicardial surface.
  
  
  RESULTS
  Two-photon excitation of di-4-aminonaphthenyl-pyridinum-propylsulfonate was used to measure electric activity at discrete epicardial layers of isolated Langendorff-perfused rabbit hearts to a depth of 500 μm. Endo-to-epicardial wavefronts were studied during right atrial or ventricular endocardial pacing. Similar measurements were made with epi-to-endocardial, transverse, and longitudinal pacing protocols. Results were compared with data from a bidomain model of 3-dimensional (3D) electric propagation within ventricular myocardium. During right atrial and endocardial pacing, AP rise time (10%-90% of upstroke) decreased by ≈50% between 500 and 50 μm from the epicardial surface, whereas conduction velocity increased and AP duration was only slightly shorter (≈4%). These differences were not observed with other conduction patterns. The depth-dependent changes in rise time were larger at higher pacing rates. Modeling data qualitatively reproduced the behavior seen experimentally and demonstrated a parallel reduction in peak I(Na) and electrotonic load as the wavefront approaches the epicardial surface.
  
  
  CONCLUSIONS
  Decreased electrotonic load at the epicardial surface results in more rapid AP upstrokes and higher conduction velocities compared with the bulk myocardium. Combined effects of tissue depth and pacing rate on AP rise time reduce conduction safety and myocardial excitability within the ventricular wall.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Allen
authors.initials: A
authors.lastname: Kelly
authors.forename: Iffath A
authors.initials: IA
authors.lastname: Ghouri
authors.forename: Ole J
authors.initials: OJ
authors.lastname: Kemi
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bishop
authors.forename: Olivier
authors.initials: O
authors.lastname: Bernus
authors.forename: Flavio H
authors.initials: FH
authors.lastname: Fenton
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Myles
authors.forename: Francis L
authors.initials: FL
authors.lastname: Burton
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D000200:Action Potentials; D000818:Animals; D002304:Cardiac Pacing, Artificial; D003198:Computer Simulation; D004699:Endocardium / Q000502:physiology; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D036641:Microscopy, Fluorescence, Multiphoton; D008955:Models, Cardiovascular; D010477:Perfusion; D010496:Pericardium / Q000502:physiology; D011726:Pyridinium Compounds; D011817:Rabbits; D013997:Time Factors; D016276:Ventricular Function; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; C050019:1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine
keywords: action potential anisotropy; di-4-aminonaphthenyl-pyridinum-propylsulfonate; electrophysiology; multiphoton microscopy