title: Model of the distribution of diastolic left ventricular posterior wall thickness in healthy adults and its impact on the behavior of a string of virtual cardiomyocytes.
abstract: Correlation of the thickness of the left ventricular posterior wall (LVPWd) with various parameters, including age, gender, weight and height, was investigated in this study using regression models. Multicenter derived database comprised over 4,000 healthy individuals. The developed models were further utilized in the in vitro-in vivo (IVIV) translation of the drug cardiac safety data with use of the mathematical model of human cardiomyocytes operating at the virtual healthy population level. LVPWd was assumed to be equivalent to the length of one-dimensional string of virtual cardiomyocyte cells which was presented, as other physiological factors, to be a parameter influencing the simulated pseudo-ECG (pseudoelectrocardiogram), QTcF and ∆QTcF, both native and modified by exemplar drug (disopyramide) after I Kr current disruption. Simulation results support positive correlation between the LVPWd and QTcF/∆QTc. Developed models allow more detailed description of the virtual population and thus inter-individual variability influence on the drug cardiac safety.
authors.affiliation: Department of Statistics, Cracow University of Economics, Krakow, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Fijorek
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Stähli
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Gielerak
authors.forename: Pawel
authors.initials: P
authors.lastname: Krzesinski
authors.forename: Beata
authors.initials: B
authors.lastname: Uzieblo-Zyczkowska
authors.forename: Pawel
authors.initials: P
authors.lastname: Smurzynski
authors.forename: Adam
authors.initials: A
authors.lastname: Stanczyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stolarz-Skrzypek
authors.forename: Kalina
authors.initials: K
authors.lastname: Kawecka-Jaszcz
authors.forename: Marek
authors.initials: M
authors.lastname: Jastrzebski
authors.forename: Mateusz
authors.initials: M
authors.lastname: Podolec
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kopec
authors.forename: Barbara
authors.initials: B
authors.lastname: Stanula
authors.forename: Maryla
authors.initials: M
authors.lastname: Kocowska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Tylutki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Polak
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001830:Body Surface Area; D003198:Computer Simulation; D016208:Databases, Factual; D003971:Diastole / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D064368:Healthy Volunteers; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D011044:Poland; D012189:Retrospective Studies; D012737:Sex Factors; D013557:Switzerland; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult