New Carro et al. Human Ventricular Cell Model

Development of a new human ventricular cell model to solve the two major criticisms to the Carro et al. 2011 [1] model:

  1. Strange form of the Action Potential before the plateau phase, and
  2. behavior of the Action Potential Duration under restitution protocols of stimulation.

General Information

Researchers: Jesús Carro, Joel Castro, José F. Rodríguez-Matas, Esther Pueyo.
DENIS version: DENIS Natrium (version 2)
App in DENIS: Carro-Rodriguez-Laguna-Pueyo Epicardial Model (Carro et al. 2011) for human ventricular cells

Description

Models of Action Potential (AP) have been largely used to study the behavior of the heart in normal or pathological conditions. One of the problems to develop these models is the difficulty to validate the model against all the known experimental situations.

On the other hand, manytimes we need to asume that the model variables are independents. As our previous research shows, this assumtion could be a problem [2]. Both problems together makes very difficult to modify a model, because in the moment you change something, many other things will change.

Actually, we are working on an optimization algorithm based on response surface aproximations to calculate the value of parameters of the model that can’t be measured directly. We simulate the cell under different protocols of stimulation and with different combination of the parameters to look for the combination that better represent the experiments. Doing it, we are able to modify several parameters at the same time, not one at a time.

We are developing a new version of the Carro et al. (2011) model [1] and we want to increase the number of parameters we can modify and the number of protocols we can test, but we need to make a lot of simulations.

Phases

  • Identification of the shape problem cause. Completed
  • Modification of the model to solve the shape problem. Completed
  • Identification of the restitution problem cause. Completed
  • Modification of the model to solve the restitution problem. Completed
  • Optimization of ionic conductances to fit physiological markers. In progress

References

[1] [pdf] [doi] J. Carro, J. F. Rodríguez, P. Laguna, and E. Pueyo, “A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions,” Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and Engineering Sciences, vol. 369, iss. 1954, pp. 4205-4232, 2011.
[Bibtex]
@article{Carro2011,
title={A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions},
author={J. Carro and Rodr{\'i}guez, Jos{\'e} F{\'e}lix and P. Laguna and E. Pueyo},
journal={Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and Engineering Sciences},
volume={369},
number={1954},
pages={4205--4232},
year={2011},
doi={10.1098/rsta.2011.0127},
url={http://dx.doi.org/10.1098/rsta.2011.0127},
publisher={The Royal Society}
}
[2] [pdf] [doi] J. Carro, J. F. Rodríguez, and E. Pueyo, “In silico simulations of experimental protocols for cardiac modeling,” in Engineering in Medicine and Biology Society (EMBC), 2014 36th Annual International Conference of the IEEE, 2014, pp. 5695-5698.
[Bibtex]
@inproceedings{Carro2014,
author={J. Carro and Rodr{\'i}guez, Jos{\'e} F{\'e}lix and E. Pueyo},
booktitle={Engineering in Medicine and Biology Society (EMBC), 2014 36th Annual International Conference of the IEEE},
title={In silico simulations of experimental protocols for cardiac modeling},
year={2014},
pages={5695-5698},
keywords={bioelectric potentials;calcium;cardiology;L-type calcium current inactivation;cardiac modeling;experimental protocols;human ventricular AP models;parameter model identification;parameter model validation;Computational modeling;Data models;Electric potential;Logic gates;Mathematical model;Protocols;Steady-state},
doi={10.1109/EMBC.2014.6944920},
url={http://dx.doir.org/10.1109/EMBC.2014.6944920},
ISSN={1557-170X},
month={Aug},}