Bridging experiments, models and simulations: an integrative approach to validation in computational cardiac electrophysiology
Open accessAbstract
Computational models in physiology often integrate functional and structural information from a large range of spatiotemporal scales from the ionic to the whole organ level. Their sophistication raises both expectations and skepticism concerning how computational methods can improve our understanding of living organisms and also how they can reduce, replace, and refine animal experiments. A fundamental requirement to fulfill these expectations and achieve the full potential of computational physiology is a clear understanding of what models represent and how they can be validated. The present study aims at informing strategies for validation by elucidating the complex interrelations among experiments, models, and simulations in cardiac electrophysiology. We describe the processes, data, and knowledge involved in the construction of whole ventricular multiscale models of cardiac electrophysiology. Our analysis reveals that models, simulations, and experiments are intertwined, in an assemblage that is a system itself, namely the model-simulation-experiment (MSE) system. We argue that validation is part of the whole MSE system and is contingent upon 1) understanding and coping with sources of biovariability; 2) testing and developing robust techniques and tools as a prerequisite to conducting physiological investigations; 3) defining and adopting standards to facilitate the interoperability of experiments, models, and simulations; 4) and understanding physiological validation as an iterative process that contributes to defining the specific aspects of cardiac electrophysiology the MSE system targets, rather than being only an external test, and that this is driven by advances in experimental and computational methods and the combination of both.
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Each entity and activity in the final set has already been mentioned for provenance, modeling or documentation purposes, or experiment design of simulation studies, but they have not all been used together.
“Each entity and activity has already been mentioned for provenance, modeling or documentation purposes, or experiment design of simulation studies [1, 3–5, 8, 20, 21, 60–63], but they have not all been used together.”
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Self-citation
- Authors
- Carusi, A., Burrage, K., & Rodríguez, B.
- Affiliations
- Norwegian University of Science and Technology (NO)
- University of Oxford (GB)
- Corresponding author
- Rodríguez, Blanca
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2012-07-15
- Volume
- 303
- Issue
- 2
- Pages
- H144-H155
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2071953960
- Cited by
- 102
- References
- 114
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 14 · 2016: 10 · 2015: 9 · 2014: 15 · 2013: 18 · 2012: 2
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Norges Forskningsråd
- Medical Research Council
- Economic and Social Research Council
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy and History of Science
- Keywords
- model validation, cardiac electrophysiology, multiscale modeling, interoperability standards, computational physiology
- MeSH terms
- Animals, Computer Simulation, Heart, Humans, Models, Cardiovascular, Rats, Validation Studies as Topic, Electrophysiological Phenomena
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