title: Tissue discontinuities affect conduction velocity restitution: a mechanism by which structural barriers may promote wave break.
abstract: BACKGROUND
  The mechanism by which structural barriers promote wave break and fibrillation is unclear. Conduction velocity (CV) restitution is an important determinant of wave break. Abnormal CV restitution is associated with ventricular fibrillation in patients with heart disease and arises preferentially in fibrotic myocardium. We hypothesize that tissue discontinuities imposed by structural barriers cause abnormal CV restitution.
  
  
  RESULTS
  Tissue discontinuities were simulated in cultures of neonatal rat heart cells grown in 8-armed star patterns. Premature stimulation was applied at the extremity of 1 arm (n=12) while extracellular electrograms were recorded at 24 sites throughout the star. Action potentials were recorded at the following 3 sites: in the stimulated arm and at the discontinuity both proximal to and distal from the star center. Extracellular recordings revealed progressive increases in activation delay (indicative for abnormal CV restitution) only at the discontinuity from arms proximal to the star center. The mean increase in delay was 0.81+/-0.41 ms/10 ms for recording sites proximal to and 3.13+/-0.58 ms/10 ms for sites distal from this discontinuity. Depolarizing currents were determined in single cells during premature stimulation and for voltage configurations similar to those arising at the discontinuity. Both voltage-clamp measurements and computer simulations showed that delay at the discontinuity was associated with biphasic, prolonged activation and delayed inactivation of depolarizing current.
  
  
  CONCLUSIONS
  Tissue discontinuities cause abnormal CV restitution. Rapid increase in activation after an initial slow activation and delayed inactivation at the discontinuity lengthen the duration of depolarizing current and cause the abnormal restitution.
authors.affiliation: Heart Lung Center Utrecht, University Medical Center, Utrecht, Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Derksen
authors.forename: Harold V M
authors.initials: HV
authors.lastname: van Rijen
authors.forename: Ronald
authors.initials: R
authors.lastname: Wilders
authors.forename: Sara
authors.initials: S
authors.lastname: Tasseron
authors.forename: Richard N W
authors.initials: RN
authors.lastname: Hauer
authors.forename: Willem L C
authors.initials: WL
authors.lastname: Rutten
authors.forename: Jacques M T
authors.initials: JM
authors.lastname: de Bakker
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003198:Computer Simulation; D004558:Electric Stimulation; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000166:cytology* / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D013997:Time Factors
chemical_list: D007473:Ion Channels