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Myomodel is an informal research agenda of a network of scientists
and engineers that develop computer models of the heart, heart
diseases and related systems and processes. We are affiliated mostly to
organisations found geographically around the mid-lower course of the
Damboviţa and Argeş rivers.
This site is a partly public repository and a gateway to
some computational resources.
Directions
The following are projects or continuous activities included in the agenda.
Electrophysiology modelling
Pathophysiology of ECG repolarisation features
This direction aims to clarify the relation between repolarisation at
membrane level, the gradients of channel densities across the myocardium
and ECG repolarisation potentials (primarily the T, U and epsilon waves).
Testing of drug effects at celluar level, simulation of effects at tissue level
Drugs are administered to cultured human myocardial cells and their effects
on activation patterns of individual channels are determined using patch-clamp
measurements. Simulations are then used to estimate effects on macroscopic
electrophysiological parameters such as conduction speed and refractory period
and thus infer potential arrhythmogeneity at various concentrations.
The whole framework is similar to CiPA methodology.
Population models for clinical prediction of myocardium pathology
Population models describe the probabilistic distribution of processes
and parameters in a human population. This distribution corresponds to predicted
rates of clinical events.
Pharmacometric models and characterisation of channelopathies
This new direction aims to develop sets of individual models that span
the range of normal and pathological parameter distributions and also
characterise the margins of normality and extreme cases such as
channelopathies.
Population models are needed to connect properties of drugs to estimations of
risk of proarrhythmia in a specific subgroup.
Population distribution of other parameters
Especially the distribution of investigation results, relevant to the
pathophysiology of cardiac disease, such as the high sensitivity troponin
levels or creatinin
levels/glomerular filtration rate
Technical framework for reproducible simulations
A continuous technical effort to achieve setups in which
simulations/computations are identifiable, fully documented,
rerunable and findable. It includes the development of a formal
language in which the specific features of each scenario, including
the differences from other scenarios can be described both in a
meaningful and concice way for the human reader and in a form that
cand be automatically processed to reproduce simulation results.
Project coordinators
Publications
- Sulea T, Draga S, Mernea M, Corlan AD, Radu BM, Petrescu AJ,
Amuzescu B, Differential inhibition by cenobamate of canonical human
Nav1.5 ion channels and several point mutants, International Journal
of Molecular Sciences, 2024,
Int. J. Mol. Sci. 2025, 26(1), 358; https://doi.org/10.3390/ijms26010358
- Mateias AL, Armasescu F, Amuzescu B, Corlan AD, Radu BM,
Inhibitory effects of cenobamate on multiple human cardiac ion
channels and possible arrhythmogenic consequences,
Biomolecules 2024, 14(12), 1582; https://doi.org/10.3390/biom14121582
- A population model of age and gender specific cardiac troponin
levels. Alexandru Dan Corlan (preprint,
doi: https://doi.org/10.1101/2024.12.20.24319414)
- [preprint] Inhibitory effects of cenobamate on multiple human cardiac
ion channels and possible arrhythmogenic consequences, Bogdan Amuzescu,
Alexandru Dan Corlan, Beatrice Mihaela Radu, 2023
https://www.researchsquare.com/article/rs-3735338/v1
https://doi.org/10.21203/rs.3.rs-3735338/v1
- Evolution of mathematical models of cardiomyocyte
electrophysiology Bogdan Amuzescu, Razvan Airini, Florin Bogdan
Epureanu, Stefan A Mann, Thomas Knott, Beatrice Mihaela Radu
https://pubmed.ncbi.nlm.nih.gov/33607174/ Math Biosci. 2021
Apr:334:108567. doi: 10.1016/j.mbs.2021.108567. Epub 2021 Feb 16.
- Transcriptomic uniqueness and commonality of the ion channels and
transporters in the four heart chambers Sanda Iacobas, Bogdan
Amuzescu, Dumitru A Iacobas https://pubmed.ncbi.nlm.nih.gov/33531573/
Sci Rep. 2021 Feb 2;11(1):2743. doi: 10.1038/s41598-021-82383-1.
- Assessment of proarrhythmogenic risk for chloroquine and
hydroxychloroquine using the CiPA concept Urs Thomet, Bogdan Amuzescu,
Thomas Knott, Stefan A Mann, Kanigula Mubagwa, Beatrice Mihaela Radu
Eur J Pharmacol. 2021 Dec 15:913:174632. doi:
10.1016/j.ejphar.2021.174632. Epub 2021 Nov 14.
- Kinetics methods for clinical epidemiology problems
A Corlan and J Ross 2015. Proc Natl Acad Sciences USA 112 (46) 14150-14155
https://doi.org/10.1073/pnas.1510927112
Supplementary material (population model of atrial fibrillation)
- Stability and sustained oscillations in a ventricular
cardiomyocyte model Bogdan Amuzescu, Adelina Georgescu, Gheorghe
Nistor, Marin Popescu, Istvan Svab, Maria-Luisa Flonta, Alexandru Dan
Corlan Interdiscip Sci. 2012 Mar;4(1):1-18. doi:
10.1007/s12539-012-0116-y. Epub 2012 Mar 6.
- Electrocardiographic patterns of early repolarization
attributable to increased transient outward current in the
subepicardial region. A simulation study. European Heart Journal (
2009 ) 30 ( Abstract Supplement ), 491
[
Abstract]
[
Poster]
- Increased transient outward current in the subepicardial region can
explain the slurring of the QRS. A simulation study.
A.D. Corlan, B.P. Amuzescu, I. Milicin, L. De Ambroggi
36-th Congress of the International Society of Cardiology, Wroclaw,
24-27 Jun 2009
- Feasibility of estimating maximum ion conductance parameters
from the shape of the action potential. A simulation study.
A.D. Corlan, B.P. Amuzescu, I. Milicin, G. Nistor,
M.N. Popescu, A. Georgescu, M.O. Vlad
Biophysical Journal, 2009, 96 (3): 664a
53-rd Annual Meeting of the Biophysical Society, Boston, 1-4 Mar 2009
- Stability and oscillations in a ventricular cardiomyocyte model
studied using the tools of dynamic systems analysis and bifurcation theory
M.N. Popescu, G. Nistor, A. Georgescu, A.D. Corlan,
B.P. Amuzescu, C.I. Barbu, M.L. Flonta
Biophysical Journal, 2009, 96 (3): 664a
53-rd Annual Meeting of the Biophysical Society, Boston, 1-4 Mar 2009
- Early repolarization (J) wave association with other repolarization features
A.D. Corlan, B.M. Horacek, L. De Ambroggi.
35-rd Congress Int. Soc. Electrocardiology, Sankt Petersburg, 18-21 Sep 2008
Funding
Some of the formal projects underlying the effort.
- PN-III-P4-PCE-2021-1422 Profilul de siguranta pentru doua
antiepileptice nou-aprobate prin analiza in vitro a riscului
proaritmogen si a transportului prin BBB 2022--2024
- Competitiveness Operational Programme 2014–2020 project
P_37_675 (contract no. 146/2016), Priority Axis 1, Action 1.1.4
- POSCCE-A2-O2.2.3-2008. Dezvoltarea unor retele de centre C-D,
coordonate la nivel national si racordate la retele europene si
internationale de profil (GRID, GEANT) 2008--2011
- (NSF/CHE-0847073, CHE-0451109) Identification of Dominant Paths
for Biochemical Reaction Networks from Incomplete Data 2007--2014
- Partnership grant PN-II-061-010 from the Romanian
National Agency for Scientic Research, 2007--2010
Affiliations
Organisations where we are/were affiliated
while participating in this research program.
- University of Bucharest, Department of
Biophysics and Physiology
- University and Emergency Hospital of Bucharest
- Carol Davila
University of Medicine and Pharmacy, Bucharest, Centre for High Performance Computing and Computational Medicine
- IRCCS San Donato, University of Milan, IT
- National Science and Technology University Politechnica Bucuresti, Applied Mathematics Department, Piteşti (formerly
University of Piteşti)
- Scalacalc Laboratory, Bucharest
- Institute of Logic and Data Science, Bucharest
Links
Older version of this site.
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