title: Towards computational modelling of the human foetal electrocardiogram: normal sinus rhythm and congenital heart block.
abstract: OBJECTIVE
  We aim to engineer a computational model of propagation during normal sinus rhythm in the foetal human heart, by modifying models for adult cardiac tissue to match foetal electrocardiogram (fECG) characteristics. The model will be partially validated by fECG data, and applied to explore possible mechanisms of arrhythmogenesis in the foetal heart.
  
  
  RESULTS
  Foetal electrocardiograms have been recorded during pregnancy, with P- and T-waves, and the QRS complex, identified by averaging and signal processing. Intervals of the fECG are extracted and used to modify currently available human adult cardiomyocyte models. RR intervals inform models of the pacemaking cells by constraining their rate, the QT interval and its rate dependence constrain models of ventricular cells, and the width of the P-wave, the QR and PR intervals constrain propagation times, conduction velocities, and intercellular coupling. These cell models are coupled into a one-dimensional (1D) model of propagation during normal sinus rhythm in the human foetal heart. We constructed a modular, heterogeneous 1D model for propagation in the foetal heart, and predicted the effects of reduction in L-type Ca(++) current. These include bradycardia and atrioventricular conduction blocks. These may account quantitatively for congenital heart block produced by positive IgG antibodies.
  
  
  CONCLUSIONS
  The fECG can be interpreted mechanistically and quantitatively by using a simple computational model for propagation. After further validation, by clinical recordings of the fECG and the electrophysiological experiments on foetal cardiac cells and tissues, the model may be used to predict the effects of maternally administered pharmaceuticals on the fECG.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Pervolaraki
authors.forename: Sam
authors.initials: S
authors.lastname: Hodgson
authors.forename: Arun V
authors.initials: AV
authors.lastname: Holden
authors.forename: Alan P
authors.initials: AP
authors.lastname: Benson
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D016275:Atrial Function / Q000502:physiology*; D003198:Computer Simulation; D004562:Electrocardiography; D005260:Female; D005318:Fetal Heart / Q000502:physiology*; D006325:Heart Atria / Q000166:cytology / Q000503:physiopathology; D006327:Heart Block / Q000151:congenital* / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology; D006801:Humans; D008955:Models, Cardiovascular; D011247:Pregnancy; D011690:Purkinje Fibers / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology; D016276:Ventricular Function / Q000502:physiology*
keywords: Congenital heart block; Electrocardiogram; Foetal; Human; Tachycardia