Numerička i eksperimentalna analiza kardiomiopatije
Numerical and experimental analysis of cardiomyopathy
Докторанд
Tomašević, SmiljanaМентор
Filipović, NenadЧланови комисије
Isailović, VeliborJovičić, Gordana
Velicki, Lazar
Saveljić, Igor
Метаподаци
Приказ свих података о дисертацијиСажетак
Iako su sprovedene brojne kliničke studije i postavljene smernice dobre
kliničke prakse, nedostaci u razumevanju mehanizama napredovanja
kardiomiopatije, stratifikaciji pacijenata u nisko- i visoko-rizične grupe, kao i
u određivanju i praćenju dejstva terapija za svakog pojedinačnog pacijenta i dalje
postoje. Praćenje progresije kardiomiopatije i pridružene aortopatije, kao i
efekata lekova na miokard, naglašava potrebu za razvojem novih metoda za bolje
razumevanje srčanih funkcija.
Data disertacija obuhvata analizu hipertrofične i dilatativne
kardiomiopatije, kao i pridruženih bolesti koje se odnose na različite stepene
aortne stenoze i utiču na srčanu hipertrofiju. Kreirani su različiti
trodimenzionalni (3D) parametarski modeli leve srčane komore, kao i 3D modeli
realne anatomske geometrije aortnog korena, i celog srca. Deo podataka iz
sprovedene kliničke studije i eksperimentalnih istraživanja kardiomiopatije
iskorišćeni su za razvoj i validaciju numeričkih modela, stratifikaciju ri...zika
od progresa kardiomiopatije, kao i za modeliranje dejstva različitih grupa lekova
na srčanu funkciju.
Kompjuterske simulacije sa 3D parametarskim modelima leve srčane komore
izvedene su pomoću spregnutih mikro- i makromodela, primenom metode konačnih
elemenata i fluid-solid interakcijom. Interakcije lekova sa kardiomiocitima
određene su u okviru eksperimentalnih istraživanja srčanog tkiva, a rezultati su
implementirani u spregnuti višeskalni model kako bi se odredio efekat
različitih grupa lekova na 3D model leve komore srca. Implementirani su aktivni
i pasivni modeli mišića. Na modelima realne anatomske geometrije simuliran je
uticaj različitih stepena aortne stenoze na odzive fluida i solida, i diskutovana
je njena povezanost sa hipertrofijom srca i aortopatijom. Predstavljene metode i
rezultati kompjuterskih simulacija za različite tipove kardiomiopatije i
pridruženih kardiovaskularnih bolesti imaće značajan uticaj na kliničke
smernice i buduće pravce lečenja pacijenata.
Although numerous clinical studies have been conducted and guidelines of good
clinical practice have been established, there are lacks in understanding the mechanisms of
cardiomyopathy progression, stratifying patients into low- and high-risk groups, as well as
determining and monitoring the effects of therapies for each individual patient. Monitoring
of cardiomyopathy progression and associated aortopathy, as well as the effects of drugs on
the myocardium, highlights the need for development of new methods to better understand
cardiac functions.
The presented dissertation includes the analysis of hypertrophic and dilated
cardiomyopathy, as well as associated diseases related to different degrees of aortic stenosis
affecting cardiac hypertrophy. Different three-dimensional (3D) parametric models of the
left heart ventricle are created, as well as the 3D patient-specific models of aortic root and
the whole heart. Part of the data from the conducted clinical and experimental studies of
c...ardiomyopathy are used for the development and validation of numerical models, risk
stratification of cardiomyopathy, as well as for modeling the effects of different drug groups
on cardiac function.
Computational simulations including 3D parametric models of the left heart ventricle
are performed using coupled micro- and macromodels, employing the finite element method
and fluid-solid interaction. Drugs interactions with cardiomyocytes are determined within
the experimental studies of heart tissue, while the results are implemented in a coupled
multiscale model to determine the effects of different drug groups on a 3D model of the left
heart ventricle. Active and passive muscle models are implemented. The influence of
different aortic stenosis severities on fluid and solid behaviour was simulated on patientspecific models, whereas its association with cardiac hypertrophy and aortopathy was
discussed. The presented methods and results of computational simulations for different
types of cardiomyopathies and associated cardiovascular diseases will have a significant
impact on clinical guidelines and future directions of patients’ treatments.