On Simulating the Effect of Sodium Channel Block on Cardiac Electromechanics

International audienceObjective: The purpose of this paper is to investigate computationally the influence of sodium ion channel block on cardiac electro-mechanics. Methods: To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles modeled. We employ the Kirchhoff active stress model to generate electrically excited contractile behavior of myofibers. Results: Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel block translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel block was found to increase left ventricular twist. Conclusion: A multiphysics computational framework from the cell level to the organ level was used to predict the effect of sodium channel blocking drugs on cardiac electromechanics. Significance: There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible

Empathy, education and awareness: A VR hackathon’s approach to tackling climate change

Climate change education is crucial for fostering informed and engaged future generations. However, traditional pedagogies often fail to engage learners fully and provide real-world, experiential learning. This paper presents a novel approach to climate change education through a three-day virtual reality (VR) hackathon. The hackathon focused on four United Nations (UN) Sustainable Development Goals (SDGs)—Quality Education, Affordable and Clean Energy, Sustainable Cities and Communities, and Climate Action. Using VR technology and game design software, engineering students worked in teams. They competed against each other in designing immersive environments that demonstrated their understanding of these SDGs and climate change. Our goal was to encourage the development of empathy, education, and awareness around these critical global issues. The hackathon also integrated authentic assessments, mirroring real-world engineering tasks and providing a more practical and relevant learning experience. Our findings suggest that this VR hackathon has significantly enhanced students’ understanding of the SDGs and climate change issues, their competency with VR technologies, as well as their teamwork and problem-solving skills. This paper discusses the hackathon’s design, implementation, and outcomes, highlighting the potential of such innovative approaches in tackling climate change education and awareness

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Proposing a Caputo-Land System for active tension. Capturing variable viscoelasticity

Accurate cell-level active tension modeling for cardiomyocytes is critical to understanding cardiac functionality on a subject-specific basis. However, cell-level models in the literature fail to account for viscoelasticity and inter-subject variations in active tension, which are relevant to disease diagnostics and drug screening, e.g., for cardiotoxicity. Thus, we propose a fractional order system to model cell-level active tension by extending Land's state-of-the-art model of cardiac contraction. Our approach features the (left) Caputo derivative of six state variables that identify the mechanistic origins of viscoelasticity in a myocardial cell in terms of the thin filament, thick filament, and length-dependent interactions. This proposed CLS is the first of its kind for active tension modeling in cells and demonstrates notable subject-specificity, with smaller mean square errors than the reference model relative to cell-level experiments across subjects, promising greater clinical relevance than its counterparts in the literature by highlighting the contribution of different cellular mechanisms to apparent viscoelastic cell behavior, and how it could vary with disease

Simulating the Effect of Sodium Channel Blockage on Cardiac Electromechanics

There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible. The purpose of this paper is to investigate computationally the influence of sodium ion channel blockage on cardiac electromechanics. To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles were modeled. We employ the Kerckhoffs active stress model to generate electrically excited contractile behavior of myofibers. Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel blockage translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel blockage was found to increase left ventricular twist. A multiphysics computational framework from the cell level to the organ level was thus used to predict the effect of sodium channel blocking drugs on cardiac electromechanics

Resolving the Diffusionless Transformation Process of Twinning in Single Crystal Plasticity Theory

This paper outlines a single crystal plasticity theory for the mesoscale resolution of the diffusionless transformation process of deformation twinning. Unlike prevalent crystal plasticity models of lattice transformation that characterize volume fraction evolution of coexisting parent and product lattices at a material point, our model alternates between two deformation gradient decompositions, depending on whether or not the lattice is transforming, so that only a single lattice exists at a material point at all times. This approach permits a proper spatiotemporal resolution of the transformation, and further captures its associated residual lattice distortions. Our formulation was implemented as a VUMAT subroutine on the finite element solver ABAQUS\Explicit and used to model the twinning of a magnesium single crystal that was loaded under compression at different angles. As verified against multiple experiments from the literature, our model successfully characterizes for moderate strain: (a) the anisotropic stress-strain behavior of the Mg crystal, (b) the resulting spatial cross-hatch pattern of spindle shaped twins, and (c) the natural completion times of the twinning transformation. These results indicate that our mesoscale theory is capable of an in-depth spatiotemporal investigation of twinning and can be potentially extended to similar diffusionless transformation processes in single crystals

On Simulating the Effect of Sodium Channel Block on Cardiac Electromechanics

Objective: The purpose of this paper is to investigate computationally the influence of sodium ion channel block on cardiac electro-mechanics. Methods: To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles modeled. We employ the Kirchhoff active stress model to generate electrically excited contractile behavior of myofibers. Results: Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel block translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel block was found to increase left ventricular twist. Conclusion: A multiphysics computational framework from the cell level to the organ level was used to predict the effect of sodium channel blocking drugs on cardiac electromechanics. Significance: There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible