Myocardium models, from protein to policy


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

  1. 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
  2. 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
  3. 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)
  4. [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
  5. 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.
  6. 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.
  7. 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.
  8. 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)
  9. 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.
  10. 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]
  11. 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
  12. 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
  13. 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
  14. 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.
  1. 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
  2. Competitiveness Operational Programme 2014–2020 project P_37_675 (contract no. 146/2016), Priority Axis 1, Action 1.1.4
  3. 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
  4. (NSF/CHE-0847073, CHE-0451109) Identification of Dominant Paths for Biochemical Reaction Networks from Incomplete Data 2007--2014
  5. 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.