Related Experiment Video
Updated: Jun 21, 2026
14:14
Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models
Published on: August 12, 2018
9.0K
Sex-specific human electromechanical multiscale in-silico models for virtual therapy evaluation
Maxx Holmes1, Zhinuo Jenny Wang1, Ruben Doste1
1Department of Computer Science, University of Oxford, Oxford, United Kingdom.
Journal of Molecular and Cellular Cardiology Plus
|September 2, 2025
Summary
Sex-specific models reveal women have increased QTc prolongation risk due to hERG inhibition, while men show T-wave amplitude reduction. Anatomical and ionic differences drive these cardiovascular drug responses.
Area of Science:
- Cardiovascular physiology
- Computational biology
- Pharmacology
Background:
- Women are underrepresented in cardiovascular research, potentially impacting treatment efficacy.
- Understanding sex-specific differences in cardiac electromechanical function is crucial for personalized medicine.
Purpose of the Study:
- To develop and validate sex-specific human cellular and biventricular electromechanical models.
- To mechanistically investigate sex-differences in cardiovascular drug responses.
Main Methods:
- Integrated protein genomic expression data with sex-specific electrophysiological and biventricular models.
- Validated models using sex-specific clinical and experimental datasets, including drug responses.
- Explored ionic mechanisms underlying sex-differences in drug response.
Main Results:
- Models accurately reproduced clinical ECG parameters (QTc, T-wave amplitude) and mechanical biomarkers (LVEF) stratified by sex.
- Ionic differences primarily drove ECG sex-characteristics, while mechanical differences resulted from combined anatomical and ionic factors.
- Simulations predicted exacerbated QTc prolongation in women with Dofetilide and T-wave amplitude reduction in men with Verapamil.
Conclusions:
- Sex differences in repolarization reserve, calcium handling, and cardiac anatomy significantly influence ECG and LVEF responses to drugs.
- Women exhibit greater QTc prolongation susceptibility under hERG inhibition, whereas men show more pronounced T-wave amplitude changes.
- Females demonstrated more preserved LVEF under calcium blockade, highlighting the interplay of ionic and anatomical factors in sex-specific drug responses.
Related Concept Videos
02:16Stereotype Content Model
The Stereotype Content Model (SCM) was first proposed by Susan Fiske and her colleagues (Fiske, Cuddy, Glick & Xu, 2002; see also Fiske, 2012 and Fiske, 2017). The SCM specifies that when someone encounters a new group, they will stereotype them based on two metrics: warmth—or that group’s perceived intent, and how likely they are to provide help or inflict harm—and competence—or their ability to carry out that objective. Depending on the warmth-competence categorization, a person will feel...
01:14Mechanical Efficiency of Real Machines
The mechanical efficiency of a machine is a fundamental concept that describes how effectively a machine can convert input work into output work. According to this concept, the efficiency of a machine is equal to the ratio of the output work to the input work. An ideal machine, meaning a machine that has no energy losses, has an efficiency of one. This implies that the input work and the output work are equal.
However, in reality, no machine can be truly ideal, and all of them experience some...
However, in reality, no machine can be truly ideal, and all of them experience some...
01:30Simplified Synchronous Machine Model
The Synchronous Machine Model is a fundamental tool in analyzing and ensuring the transient stability of power systems. This model simplifies the representation of a synchronous machine under balanced three-phase positive-sequence conditions, assuming constant excitation and ignoring losses and saturation. The model is pivotal for understanding the behavior of synchronous generators connected to a power grid, particularly during transient events.
In this model, each generator is connected to a...
In this model, each generator is connected to a...
01:25Multimachine Stability
Multimachine stability analysis is crucial for understanding the dynamics and stability of power systems with multiple synchronous machines. The objective is to solve the swing equations for a network of M machines connected to an N-bus power system.
In analyzing the system, the nodal equations represent the relationship between bus voltages, machine voltages, and machine currents. The nodal equation is given by:
In analyzing the system, the nodal equations represent the relationship between bus voltages, machine voltages, and machine currents. The nodal equation is given by:
01:24Wind Turbine Machine Models
In the growing field of wind energy, incorporating wind turbine models into transient stability analysis is essential. Induction and synchronous machines are the primary models used, with induction machines being prevalent due to their simplicity and reliability.
Induction machines interact through the rotating magnetic field generated by the stator and the rotor. The key parameter is slip, which is the difference between synchronous speed and rotor speed relative to synchronous speed. Slip is...
Induction machines interact through the rotating magnetic field generated by the stator and the rotor. The key parameter is slip, which is the difference between synchronous speed and rotor speed relative to synchronous speed. Slip is...
01:21Mechanistic Models: Overview of Compartment Models
Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...