Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work
Аутори
Tomasević, SmiljanaMilosević, Miljan
Milicević, Bogdan
Simić, Vladimir
Prodanović, Momcilo
M. Mijailović, Srboljub
Filipović, Nenad
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт
Analysis of myocardial work is essential in determination of left ventricle ejection fraction (LVEF)
and non-invasive assessment of different types of cardiomyopathies. Two major classifications of
cardiomyopathy are: dilated (DCM) and hypertrophic (HCM) cardiomyopathy. Although there are
clinical improvements in cardiomyopathy risk assessment, patients are still under high risk of severe
events. Computational modeling of and computer-aided drug design can significantly advance the
understanding of cardiac muscle activity in DCM and HCM cardiomyopathies, speed up the drug
discovery and reduce the risk of severe events, aiming to improve the treatment of cardiomyopathy.
The main advantage and novelty of presented study are coupled macro and micro simulations into the
integrated Fluid Solid Interaction (FSI) system and its application for examination of heart behavior and
drug interactions. In contrary to detailed and patient-specific models where FSI analyses are very timeconsu...ming,
our models are parametric and based on dimensions of specific LV components. FSI algorithm
within the PAK software is used for modeling the LV with nonlinear material model, together with stretches
integration along muscle fibers. The methods are integrated within the SILICOFCM platform, and aim to
propose an advanced approach for the assessment of work indices and biomechanical characteristics of
cardiomyopathies and drugs effects, based on computational modelling.
In this study, simulations of the effect of drugs on improving performance of DCM LV parametric model
include the drugs that affect calcium transients (Dygoxin) and changes in kinetic parameters (2-deoxy
adenosine triphosphate - dATP). Myocardial word is presented through changes of pressures and
volumes (P-V diagrams) for DCM LV model at basic condition (without administered drug) and with using
Dygoxin and dATP. Due to increased LV size, the P-V loop for the DCM model without administered drug
is shifted toward lower ventricular pressure and lager ventricular volume, with LVEF = 56.83%. Effects of
drugs on DCM show an increase in ventricular peak pressures and LVEFs, while the P-V loops are shifted
toward decreased volumes, corresponding to healthy hearts.
Computational modeling and drug design approaches can speed up the drug discovery and
significantly reduce expenses aiming to improve the treatment of cardiomyopathy
Кључне речи:
computational modelling / myocardial work / dilated cardiomyopathy / drug effectsИзвор:
4th Belgrade Bioinformatics Conference, 2023, 4, 42-42Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Финансирање / пројекти:
- SILICOFCM - In Silico trials for drug tracing the effects of sarcomeric protein mutations leading to familial cardiomyopathy (EU-H2020-777204)
- SGABU (Grant agreement 952603)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200378 (Институт за информационе технологије, Крагујевац) (RS-MESTD-inst-2020-200378)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200107 (Универзитет у Крагујевцу, Факултет инжењерских наука) (RS-MESTD-inst-2020-200107)
Напомена:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Tomasević, Smiljana AU - Milosević, Miljan AU - Milicević, Bogdan AU - Simić, Vladimir AU - Prodanović, Momcilo AU - M. Mijailović, Srboljub AU - Filipović, Nenad PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1980 AB - Analysis of myocardial work is essential in determination of left ventricle ejection fraction (LVEF) and non-invasive assessment of different types of cardiomyopathies. Two major classifications of cardiomyopathy are: dilated (DCM) and hypertrophic (HCM) cardiomyopathy. Although there are clinical improvements in cardiomyopathy risk assessment, patients are still under high risk of severe events. Computational modeling of and computer-aided drug design can significantly advance the understanding of cardiac muscle activity in DCM and HCM cardiomyopathies, speed up the drug discovery and reduce the risk of severe events, aiming to improve the treatment of cardiomyopathy. The main advantage and novelty of presented study are coupled macro and micro simulations into the integrated Fluid Solid Interaction (FSI) system and its application for examination of heart behavior and drug interactions. In contrary to detailed and patient-specific models where FSI analyses are very timeconsuming, our models are parametric and based on dimensions of specific LV components. FSI algorithm within the PAK software is used for modeling the LV with nonlinear material model, together with stretches integration along muscle fibers. The methods are integrated within the SILICOFCM platform, and aim to propose an advanced approach for the assessment of work indices and biomechanical characteristics of cardiomyopathies and drugs effects, based on computational modelling. In this study, simulations of the effect of drugs on improving performance of DCM LV parametric model include the drugs that affect calcium transients (Dygoxin) and changes in kinetic parameters (2-deoxy adenosine triphosphate - dATP). Myocardial word is presented through changes of pressures and volumes (P-V diagrams) for DCM LV model at basic condition (without administered drug) and with using Dygoxin and dATP. Due to increased LV size, the P-V loop for the DCM model without administered drug is shifted toward lower ventricular pressure and lager ventricular volume, with LVEF = 56.83%. Effects of drugs on DCM show an increase in ventricular peak pressures and LVEFs, while the P-V loops are shifted toward decreased volumes, corresponding to healthy hearts. Computational modeling and drug design approaches can speed up the drug discovery and significantly reduce expenses aiming to improve the treatment of cardiomyopathy PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work EP - 42 SP - 42 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_1980 ER -
@conference{ author = "Tomasević, Smiljana and Milosević, Miljan and Milicević, Bogdan and Simić, Vladimir and Prodanović, Momcilo and M. Mijailović, Srboljub and Filipović, Nenad", year = "2023", abstract = "Analysis of myocardial work is essential in determination of left ventricle ejection fraction (LVEF) and non-invasive assessment of different types of cardiomyopathies. Two major classifications of cardiomyopathy are: dilated (DCM) and hypertrophic (HCM) cardiomyopathy. Although there are clinical improvements in cardiomyopathy risk assessment, patients are still under high risk of severe events. Computational modeling of and computer-aided drug design can significantly advance the understanding of cardiac muscle activity in DCM and HCM cardiomyopathies, speed up the drug discovery and reduce the risk of severe events, aiming to improve the treatment of cardiomyopathy. The main advantage and novelty of presented study are coupled macro and micro simulations into the integrated Fluid Solid Interaction (FSI) system and its application for examination of heart behavior and drug interactions. In contrary to detailed and patient-specific models where FSI analyses are very timeconsuming, our models are parametric and based on dimensions of specific LV components. FSI algorithm within the PAK software is used for modeling the LV with nonlinear material model, together with stretches integration along muscle fibers. The methods are integrated within the SILICOFCM platform, and aim to propose an advanced approach for the assessment of work indices and biomechanical characteristics of cardiomyopathies and drugs effects, based on computational modelling. In this study, simulations of the effect of drugs on improving performance of DCM LV parametric model include the drugs that affect calcium transients (Dygoxin) and changes in kinetic parameters (2-deoxy adenosine triphosphate - dATP). Myocardial word is presented through changes of pressures and volumes (P-V diagrams) for DCM LV model at basic condition (without administered drug) and with using Dygoxin and dATP. Due to increased LV size, the P-V loop for the DCM model without administered drug is shifted toward lower ventricular pressure and lager ventricular volume, with LVEF = 56.83%. Effects of drugs on DCM show an increase in ventricular peak pressures and LVEFs, while the P-V loops are shifted toward decreased volumes, corresponding to healthy hearts. Computational modeling and drug design approaches can speed up the drug discovery and significantly reduce expenses aiming to improve the treatment of cardiomyopathy", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work", pages = "42-42", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_1980" }
Tomasević, S., Milosević, M., Milicević, B., Simić, V., Prodanović, M., M. Mijailović, S.,& Filipović, N.. (2023). Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 42-42. https://hdl.handle.net/21.15107/rcub_imagine_1980
Tomasević S, Milosević M, Milicević B, Simić V, Prodanović M, M. Mijailović S, Filipović N. Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work. in 4th Belgrade Bioinformatics Conference. 2023;4:42-42. https://hdl.handle.net/21.15107/rcub_imagine_1980 .
Tomasević, Smiljana, Milosević, Miljan, Milicević, Bogdan, Simić, Vladimir, Prodanović, Momcilo, M. Mijailović, Srboljub, Filipović, Nenad, "Computational Modelling of Drug Effects on Cardiomyopathy and Analysis of Myocardial Work" in 4th Belgrade Bioinformatics Conference, 4 (2023):42-42, https://hdl.handle.net/21.15107/rcub_imagine_1980 .