1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Forced to cooperate Dupuis2018 год

Forced to cooperate
dissertation

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: In this thesis, we aim to build a computational model of sarcomere mechanics that is based on a novel hypothesis for the mechanism of cooperativity in cardiac muscle.We suggest that there is an intrinsic chemical cooperativity in the myocardium that is boosted by the mechanical tension in the muscle.We construct our model step-bystep from the ability to mimic the most basic static experiments towards the ability to mimic the shortening and relengthening of myocardial tissue that characterizes the rhythmic contraction and relaxation in the heart.Because the model is developed for eventual use in understanding clinically relevant problems in the human heart, we implement the newly developed sarcomere contraction model in a modeling framework of the circulation.As a first test, the combined model is applied to understand the relationship between cellular level mechanics and organ level hemodynamics in a heart with dyssynchronous activation patterns. Outline of ThesisExperiments have been performed in which cardiac muscle cells are skinned to allow control of the Ca 2+ concentration ([Ca 2+ ]) in the intracellular space.In these experiments, [Ca 2+ ] is held constant and the steady-state isometric tension is measured (2, 3).We utilize these results for comparison to our work in Chapter 2 where we implement our novel hypothesis of cardiac cooperativity in a computational model of the sarcomere called the MechChem model of mechano-chemical interactions in the cardiac sarcomere.The MechChem model is tested with the conditions of static skinned muscle experiments (6).In addition, we present background on sarcomere physiology.As a next step, we implement time dependence in the MechChem model.In a physiological situation, the free calcium concentration in the cytoplasm rises and falls in time.Relaxation begins when calcium concentration in the cytoplasm decreases due to extrusion of Ca 2+ through various channels and pumps.Cardiomyocytes do not reach steady state tension because they must relax before the next heartbeat.While experiments have shown that greater peak tension in the thin filament results in Chapter 2 Mechano-chemical interactions in cardiac sarcomere contraction: A computational modeling study This chapter is based on:
Год издания: 2018
Авторы: Dupuis
Другие ссылки: cris.maastrichtuniversity.nl (PDF)
doi.org (HTML)
Research Publications (Maastricht University) (PDF)
Research Publications (Maastricht University) (HTML)
Research Publications (Maastricht University) (HTML)
Research Publications (Maastricht University) (HTML)
Research Publications (Maastricht University) (HTML)