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Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges

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Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation : Recent advances and future challenges. / Vagos, Márcia R.S.S.; van Herck, Ilsbeth G.M.; Sundnes, Joakim; Arevalo, Hermenegild J.; Edwards, Andrew G.; Koivumäki, Jussi T.

In: Frontiers in Physiology, Vol. 9, No. SEP, 1221, 04.09.2018.

Research output: Contribution to journalReview ArticleScientificpeer-review

Harvard

Vagos, MRSS, van Herck, IGM, Sundnes, J, Arevalo, HJ, Edwards, AG & Koivumäki, JT 2018, 'Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges', Frontiers in Physiology, vol. 9, no. SEP, 1221. https://doi.org/10.3389/fphys.2018.01221

APA

Vagos, M. R. S. S., van Herck, I. G. M., Sundnes, J., Arevalo, H. J., Edwards, A. G., & Koivumäki, J. T. (2018). Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges. Frontiers in Physiology, 9(SEP), [1221]. https://doi.org/10.3389/fphys.2018.01221

Vancouver

Author

Vagos, Márcia R.S.S. ; van Herck, Ilsbeth G.M. ; Sundnes, Joakim ; Arevalo, Hermenegild J. ; Edwards, Andrew G. ; Koivumäki, Jussi T. / Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation : Recent advances and future challenges. In: Frontiers in Physiology. 2018 ; Vol. 9, No. SEP.

Bibtex - Download

@article{f03c8397eb5e460ea381e5a6b411855b,
title = "Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges",
abstract = "The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.",
keywords = "Atrial fibrillation, Computational modeling, Drug therapies, In silico drug screening, Pathophysiology, Pharmacodynamics, Pharmacology",
author = "Vagos, {M{\'a}rcia R.S.S.} and {van Herck}, {Ilsbeth G.M.} and Joakim Sundnes and Arevalo, {Hermenegild J.} and Edwards, {Andrew G.} and Koivum{\"a}ki, {Jussi T.}",
year = "2018",
month = "9",
day = "4",
doi = "10.3389/fphys.2018.01221",
language = "English",
volume = "9",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers",
number = "SEP",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation

T2 - Recent advances and future challenges

AU - Vagos, Márcia R.S.S.

AU - van Herck, Ilsbeth G.M.

AU - Sundnes, Joakim

AU - Arevalo, Hermenegild J.

AU - Edwards, Andrew G.

AU - Koivumäki, Jussi T.

PY - 2018/9/4

Y1 - 2018/9/4

N2 - The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

AB - The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

KW - Atrial fibrillation

KW - Computational modeling

KW - Drug therapies

KW - In silico drug screening

KW - Pathophysiology

KW - Pharmacodynamics

KW - Pharmacology

U2 - 10.3389/fphys.2018.01221

DO - 10.3389/fphys.2018.01221

M3 - Review Article

VL - 9

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - SEP

M1 - 1221

ER -