MS02 - CARD-02 Part 2 of 3

Novel multiscale and multisystem approaches to cardiovascular modeling and simulation (Part 2)

Monday, July 14 from 4:00pm - 5:40pm in Salon 4

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Note: this minisymposia has multiple sessions. The other sessions are: Part-1 and Part-3.

Mitchel J. Colebank (University of South Carolina), Vijay Rajagopal, The University of Melbourne, Australia

Description:

Cardiovascular models are now recognized as a potential frontier in the development of personalized models and digital twins. This new excitement in the field is fueling new strides in mathematical and computational approaches to describe cardiovascular function across different temporal and/or spatial scales. In addition, new multisystem models accounting for how the heart and vasculature interact with other organ systems are being developed in combination with tools located at the heart of data science. Thus, this minisymposium will focus on the development of cardiovascular models that mimic cardiovascular function across spatial or temporal scale, new models that couple the cardiovascular system with other physiological systems, and new innovations in data-driven solutions to modeling cardiovascular phenomena. Potential topics include: - Multiscale models of cardiac and vascular function; - Computational approaches to cell-tissue-organ level function; - Mathematical coupling of cardiac and vascular mechanics; - Modeling autonomic control and neurovascular function; - Simulating tissue growth and remodeling; - Multisystems models of cardiovascular-organ interactions; and - Physics-informed data science approaches to cardiovascular science

Room assignment: Salon 4

Ishraq U Ahmed

University of Sydney

"Death out of balance: cell necrosis and defective efferocytosis in a model for early atherosclerotic plaque tissue"

The resolution of chronic inflammation involves a dynamic balance between cell death and the clearance of dying cells via efferocytosis. In nonresolving atherosclerotic plaques, this balance is disrupted due to the the impairment of normal macrophage function. The accumulation of excess cholesterol by plaque macrophages promotes unprogrammed necrotic cell death, and the resulting necrotic material is less readily cleared by live macrophages. Macrophage efferocytic ability itself can also become impaired. The combination of poor efferocytosis and increased cell death rates can overwhelm live macrophages' ability to clear dying cells, eventually leading to the formation of a necrotic core. In this talk, we present a free boundary multiphase model for the early development of atherosclerotic tissue, where macrophages can undergo both apoptotic (programmed) and necrotic cell death. We show how high rates of cell death and low rates of efferocytosis can lead to a plaque populated mostly by dead material. We use multiple timescale analysis of a related spatially homogeneous ODE model to analyse how plaque tissue composition evolves in the short and long term, where the dynamics are dominated by apoptosis and necrosis respectively. We show in particular that healthy efferocytosis can lead to a short timescale equilibrium where live macrophages and apoptotic cells coexist, and that the onset of necrosis affects the stability of this equilibrium. We also consider how the availability (or lack thereof) of live cells in the deep plaque impacts cell emigration and plaque growth.

Pak-Wing Fok

University of Delaware

"Impact of Medial Calcification on Arterial Mechanics and Hemodynamics"

Medial Arterial Calcification (MAC) often occurs in aging arteries, promoted by diabetes mellitus and chronic kidney disease. Advanced MAC represents a frequent cause of chronic limb-threatening ischemia and limb amputation. Through a 1D haemodynamics simulation, we study how the mechanical properties of calcified arterial tissue and hydraulic resistance in the peripheral circulation jointly impact hemodynamics as MAC develops. We find that (i) there is a greater drop in systolic pressure across calcified arteries compared to healthy arteries, but this drop can be offset by greater peripheral resistance, provided left ventricular function is intact, (ii) both calcification and enhanced peripheral resistance lead to reduced flow rates, reduced peripheral perfusion, and peripheral tissue hypoxemia and (iii) pressurized calcified arteries present lumen areas that are smaller compared to healthy arteries, even though they are larger when unpressurized. Our simulations suggest that the increased impedance in calcified arteries results from smaller in-vivo lumen areas. This can reduce the outflow rate, but the effect is complicated by arteriole closures, vessel geometry, and global pressure. These findings confirm previously reported observations of flow reduction in calcified arteries.

Laura Ellwein Fix

Virginia Commonwealth University

"A closed-loop system-level model of cerebrovascular reactivity"

Cerebrovascular reactivity (CVR) is a metric of the ability of cerebral blood vessel tone to respond to stimuli for regulating blood flow and metabolism in the brain. In one such mechanism, the cerebrovasculature dilates to lower resistance in response to increased arterial carbon dioxide (CO2), thereby increasing blood flow to wash out the CO2. However, the integration of this with other processes and the implications for the systemic circulation are still not fully understood. Previously, Ellwein et al. developed a closed-loop system-level circulation model, in which cerebrovascular resistance was modeled using a piecewise linear function parameterized empirically using available data for blood flow velocity in the middle cerebral artery, arterial blood pressure, and expired CO2. In the current work we replaced the piecewise linear function with a more mechanistic representation of cerebral resistance as a function of partial pressure of CO2 together with a first-order control equation. Initial model simulated dynamics compare well to those previously achieved by Ellwein et al., with improved physiological fidelity. We also incorporated systemic responses to CO2 and optimized model parameters against a new cohort of data obtained under CO2 rebreathing conditions. These model adaptations will improve understanding of the system-level integration of mechanisms behind CBF regulation and CVR.

Liam Murray

The University of Melbourne

"Myofibril networks produce shear stress in sheep cardiomyocytes"

Myofibril arrangement is critical to cardiac muscle function in health, exercise, and disease. Historically, analysis of myofibril organisation impact on force and cell contraction has relied on the assumption of parallel, longitudinal arrays. However, improvements in imaging indicate that myofibrils may form complex networks. How these anisotropic networks modulate cell-contraction and force has yet to be explored. Here, morphological analysis of sheep cardiomyocytes has informed finite element models of cell contraction. Analysis of U-NET++ segmentations of Z-Discs demonstrate that myofibrils have a distribution of orientation throughout the cell. Simulations have similarly produced unique deformation patterns for geometries informed by myofibril orientations. These patterns highlight the physiological impact of myofibril structure and update understanding of uniaxial contraction to consider shear stress.

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Annual Meeting for the Society for Mathematical Biology, 2025.