title: Virtual population generator for human cardiomyocytes parameters: in silico drug cardiotoxicity assessment.
abstract: BACKGROUND
  The anatomical and histological parameters of the human ventricle depend on many factors including age and sex. Myocyte volume and electric capacitance are significant physiological parameters of left ventricle cardiomyocyte mathematical models. They allow the assessment of inter-individual variability during in vitro-in vivo extrapolation of the drug cardiotoxic effect.
  
  
  OBJECTIVE
  The current research was carried out to analyze the relationship between age, human left ventricle cardiomyocyte volume, and electric capacitance in a healthy population.
  
  
  METHODS
  In order to collect data describing cardiomyocyte volume and membrane area, literature searches were performed. It was assumed that the cardiomyocyte volume (VOL) and area (AREA) distribution have non-negative support and are skewed to the right. A log-linear model with constant variance was used. A simulation study was run to assess the influence of physiological parameters on action potential duration.
  
  
  RESULTS
  The coefficient of determination for the proposed model R(2) = 0.95, that is, 95% of the variability observed in log cardiomyocyte volume can be explained by the estimated regression equation. To allow simple calculation and model performance validation, a simple Excel file was developed (Supplementary material).
  
  
  CONCLUSIONS
  To the best of our knowledge, there is no other model available, combining age, cardiomyocyte volume, and area. The main limitations of the proposed models result from the assumptions made at the data analysis stage. The limited amount of information available in the literature and the lack of differentiation between sexes results in one common equation. The developed model is a part of the computational system for drug cardiotoxicity assessment.
authors.affiliation: Unit of Pharmacoepidemiology and Pharmacoeconomics, Cracow University of Economics, Kraków, Poland. spolak@cm-uj.krakow.pl
authors.forename: Sebastian
authors.initials: S
authors.lastname: Polak
authors.forename: Kamil
authors.initials: K
authors.lastname: Fijorek
authors.forename: Anna
authors.initials: A
authors.lastname: Glinka
authors.forename: Barbara
authors.initials: B
authors.lastname: Wisniowska
authors.forename: Aleksander
authors.initials: A
authors.lastname: Mendyk
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology; D054849:Cardiac Electrophysiology; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D003198:Computer Simulation; D064420:Drug-Related Side Effects and Adverse Reactions; D025802:Electric Capacitance; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018675:Toxicity Tests / Q000379:methods