Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. A detailed mathematical model of the human atrial cardiomyocyte: integration of electrophysiology and cardiomechanics
 
research article

A detailed mathematical model of the human atrial cardiomyocyte: integration of electrophysiology and cardiomechanics

Mazhar, Fazeelat
•
Bartolucci, Chiara
•
Regazzoni, Francesco
Show more
September 1, 2024
Journal Of Physiology-london

Mechano-electric regulations (MER) play an important role in the maintenance of cardiac performance. Mechano-calcium and mechano-electric feedback (MCF and MEF) pathways adjust the cardiomyocyte contractile force according to mechanical perturbations and affects electro-mechanical coupling. MER integrates all these regulations in one unit resulting in a complex phenomenon. Computational modelling is a useful tool to accelerate the mechanistic understanding of complex experimental phenomena. We have developed a novel model that integrates the MER loop for human atrial cardiomyocytes with proper consideration of feedforward and feedback pathways. The model couples a modified version of the action potential (AP) Koivum & auml;ki model with the contraction model by Quarteroni group. The model simulates iso-sarcometric and isometric twitches and the feedback effects on AP and Ca2+-handling. The model showed a biphasic response of Ca2+ transient (CaT) peak to increasing pacing rates and highlights the possible mechanisms involved. The model has shown a shift of the threshold for AP and CaT alternans from 4.6 to 4 Hz under post-operative atrial fibrillation, induced by depressed SERCA activity. The alternans incidence was dependent on a chain of mechanisms including RyRs availability time, MCF coupling, CaMKII phosphorylation, and the stretch levels. As a result, the model predicted a 10% slowdown of conduction velocity for a 20% stretch, suggesting a role of stretch in creation of substrate formation for atrial fibrillation. Overall, we conclude that the developed model provides a physiological CaT followed by a physiological twitch. This model can open pathways for the future studies of human atrial electromechanics.

  • Details
  • Metrics
Type
research article
DOI
10.1113/JP283974
Web of Science ID

WOS:001324651400004

PubMed ID

37641426

Author(s)
Mazhar, Fazeelat

University of Bologna

Bartolucci, Chiara

University of Bologna

Regazzoni, Francesco

Polytechnic University of Milan

Paci, Michelangelo

Tampere University

Dede', Luca

Polytechnic University of Milan

Quarteroni, Alfio  

École Polytechnique Fédérale de Lausanne

Corsi, Cristiana

University of Bologna

Severi, Stefano

University of Bologna

Date Issued

2024-09-01

Publisher

WILEY

Published in
Journal Of Physiology-london
Volume

602

Issue

18

Start page

4543

End page

4583

Subjects

Ca2+-handling

•

cardiomechanics

•

computational modelling

•

contractility

•

coupling

•

human atrial cells

•

rate adaptation

•

stretch activated currents

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
PH-SB  
FunderFunding(s)Grant NumberGrant URL

Ministry of Education, Universities and Research (MIUR)

2017AXL54F

European Union- Next GenerationEU through the Italian Ministry of University and Research

PNRR- M4C2-I1.3;PR_00000019;CUP J33C22002920006

Available on Infoscience
January 28, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/245849
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés