Multiscale simulations of left ventricular growth and remodeling

Mirzaei, Hossein; Mann, Charles K.; Rockward, Alexus; Mehri, Mohammad; Mojumder, Joy; Lee, Lik-Chuan; Campbell, Kenneth S.; Wenk, Jonathan F.

doi:10.1007/s12551-021-00826-5

Cited by 18 publications

(12 citation statements)

References 157 publications

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“…This will be important for future work that will use PyMyoVent to simulate cardiac growth and biological remodeling because Kerchoffs (Kerckhoffs et al 2012) and Witzenberg and Holmes (Witzenburg and Holmes 2019) have shown that the arterial pressure has an important impact on these processes. This issue was also discussed in a recent review (Sharifi et al 2021).…”

Section: Scope Of This Workmentioning

confidence: 85%

A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone

Mirzaei

Mann

Wenk

et al. 2022

Biomech Model Mechanobiol

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Multiscale models of the cardiovascular system can provide new insights into physiological and pathological processes. PyMyoVent is a computer model that bridges from molecular to organ-level function and which simulates a left ventricle pumping blood through the systemic circulation. Initial work with PyMyoVent focused on the End Systolic Pressure Volume Relationship and ranked potential therapeutic strategies by their impact on contractility. This manuscript extends the PyMyoVent framework by adding closed loop feedback control of arterial pressure. The control algorithm mimics important features of the physiological baroreflex and was developed as part of a long-term program that focuses on growth and biological remodeling. Inspired by the underlying biology, the reflex algorithm uses an afferent signal derived from arterial pressure to drive a kinetic model that mimics the net result of neural processing in the medulla and cell-level responses to autonomic drive. The kinetic model outputs control signals that are constrained between limits that represent maximum parasympathetic and maximum sympathetic drive and which modulate heart rate, intracellular Ca 2+ dynamics, the molecular-level function of both the thick and the thin myofilaments, and vascular tone. Simulations show that the algorithm can regulate mean arterial pressure at user-defined set-points as well as maintaining arterial pressure when challenged by changes in blood volume and/or valve resistance. The reflex also regulates arterial pressure when cell-level contractility is modulated to mimic the idealized impact of myotropes. These capabilities will be important for future work that uses computer modeling to investigate clinical conditions and treatments.

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Section: Scope Of This Workmentioning

confidence: 85%

A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone

Mirzaei

Mann

Wenk

et al. 2022

Biomech Model Mechanobiol

Self Cite

View full text Add to dashboard Cite

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“…Especially as more structural data of the myofilament become available, further development of multiscale modeling approaches will be necessary to accommodate predictions from disparate simulation approaches suitable for different system sizes and timescales. Here, efforts to reconstruct dynamic models of whole-heart function from cell-based descriptors ( Trayanova and Rice, 2011 ; Niederer et al, 2019 ; Timmermann et al, 2019 ), and myofilament contraction from filament-level molecular interactions ( Fenwick et al, 2017 ; Powers et al, 2019 ; de Winter et al, 2020 ; Creso and Campbell, 2021 ; Sharifi et al, 2021 ; Kosta et al, 2022 ), could provide essential guidance toward the incorporation of molecular-resolution data from a variety of MAPIDs. Importantly, these approaches represent the first steps toward combining different data sets that can be conflicting and overlapping at different resolutions.…”

Section: Computational Modeling and Characterization Of Mapidsmentioning

confidence: 99%

Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling

Sun

Kekenes‐Huskey

2023

Quart. Rev. Biophys.

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The cardiac sarcomere is a cellular structure in the heart that enables muscle cells to contract. Dozens of proteins belong to the cardiac sarcomere, which work in tandem to generate force and adapt to demands on cardiac output. Intriguingly, the majority of these proteins have significant intrinsic disorder that contributes to their functions, yet the biophysics of these intrinsically disordered regions (IDRs) have been characterized in limited detail. In this review, we first enumerate these myofilament-associated proteins with intrinsic disorder (MAPIDs) and recent biophysical studies to characterize their IDRs. We secondly summarize the biophysics governing IDR properties and the state-of-the-art in computational tools toward MAPID identification and characterization of their conformation ensembles. We conclude with an overview of future computational approaches toward broadening the understanding of intrinsic disorder in the cardiac sarcomere.

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“…A phenomenological growth law capable of describing the clinically relevant reverse remodeling was proposed by Lee et al ( Lee et al, 2015 ). Growth laws that rigorously capture the underlying biology and tissue microstructure are still relatively rare, as discussed in the recent reviews by Niestrawska et al ( Niestrawska et al, 2020 ) and Sharifi et al ( Sharifi et al, 2021 ).…”

Section: Multiscale Models Of Rv Mechanics and Remodelingmentioning

confidence: 99%

Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload

et al. 2022

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Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients.

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Multiscale simulations of left ventricular growth and remodeling

Cited by 18 publications

References 157 publications

A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone

A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone

Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling

Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload

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