Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.

British Journal of Pharmacology
G R MiramsDenis Noble

Abstract

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore how a compound, interfering with specific ion-channel function, may explain effects at the cell-, tissue- and organ-scales. With the advent of high-throughput screening of multiple ion channels in the wet-lab, and improvements in computational modelling of their effects on cardiac cell activity, more reliable prediction of pro-arrhythmic risk is becoming possible at the earliest stages of drug development. In this paper, we review the current use of biophysically detailed mathematical models of cardiac myocyte electrical activity in drug safety testing, and suggest future directions to employ the full potential of this approach.

References

Feb 1, 1976·British Heart Journal·D M Krikler, P V Curry
May 22, 1989·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·F G Ball, M S Sansom
Mar 1, 1989·Circulation·A M Katz, P B Katz
Sep 1, 1980·Cardiovascular Research·D Noble
May 1, 1981·The Journal of Physiology·D DiFrancesco
May 1, 1983·The Journal of General Physiology·B P BeanR W Tsien
Feb 28, 1998·The Journal of Membrane Biology·D B Tikhonov, L G Magazanik
Jul 3, 1999·BMJ : British Medical Journal·S Gottlieb
Oct 26, 1999·Cardiovascular Research·P C Viswanathan, Y Rudy
May 8, 2001·Trends in Pharmacological Sciences·J I VandenbergT J Campbell
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Denis Noble
Oct 24, 2002·The Journal of Clinical Investigation·Augustus O GrantSilvia Priori
Dec 28, 2002·Annals of the New York Academy of Sciences·Denis Noble
May 6, 2004·Medical & Biological Engineering & Computing·M Pásek, J Simurda
Jun 3, 2004·Journal of Pharmacological and Toxicological Methods·Jean-Pierre ValentinLuc Hondeghem
Oct 9, 2004·Progress in Biophysics and Molecular Biology·Alan GarnyPeter Kohl
Dec 29, 2004·Cardiovascular Research·Patrizia CamellitiPeter Kohl
Feb 16, 2005·British Journal of Pharmacology·Jason S CordesJun Zhou
May 13, 2005·European Heart Journal·Sabine M J M StrausBruno H Ch Stricker
Jun 7, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Zhilin Qu, James N Weiss
Aug 3, 2005·Annals of Biomedical Engineering·Beatriz TrénorFulgencio Montilla
Nov 18, 2005·Journal of Pharmacological and Toxicological Methods·Peter Hoffmann, Barbara Warner
Mar 28, 2006·American Journal of Physiology. Heart and Circulatory Physiology·K H W J ten Tusscher, A V Panfilov

❮ Previous
Next ❯

Citations

Mar 22, 2013·PLoS Computational Biology·Gary R MiramsDavid J Gavaghan
May 7, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Barbara WiśniowskaSebastian Polak
Jul 30, 2014·Life Sciences·Patric GlynnThomas J Hund
Nov 2, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Axel LoeweGunnar Seemann
Feb 20, 2016·Drug Discovery Today·Mark R DaviesLiudmila Polonchuk
Nov 5, 2014·British Journal of Pharmacology·Yongfeng YuanHenggui Zhang
Feb 20, 2016·Nature Reviews. Drug Discovery·Gary GintantNorman Stockbridge
Jan 21, 2016·Biophysical Journal·Jonathan CooperGary R Mirams
Nov 28, 2015·Journal of Molecular and Cellular Cardiology·Ross H JohnstoneGary R Mirams
Aug 1, 2015·CPT: Pharmacometrics & Systems Pharmacology·J-P BoisselF-H Boissel
Nov 30, 2013·British Journal of Clinical Pharmacology·Robert B KleimanJoel Morganroth
Nov 12, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Drieke VandammeWalter Kolch
Apr 30, 2013·Journal of Pharmacological and Toxicological Methods·Kylie A BeattieGary R Mirams
May 9, 2013·Journal of Pharmacological and Toxicological Methods·Ryan C ElkinsGary R Mirams
Oct 22, 2013·Drug Discovery Today·Sebastian PolakAleksander Mendyk
Aug 5, 2014·Journal of Pharmacological and Toxicological Methods·Gary R MiramsNajah Abi-Gerges
Feb 11, 2015·Progress in Biophysics and Molecular Biology·Pras PathmanathanRichard A Gray
Mar 19, 2016·The Journal of Physiology·Gary R MiramsRichard H Clayton
May 6, 2017·International Journal for Numerical Methods in Biomedical Engineering·Daniel E HurtadoPedro Madrid
Jan 24, 2014·American Journal of Therapeutics·J Rick TurnerSnehal Kothari
May 26, 2020·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Chon Lok LeiGary R Mirams
May 26, 2020·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Chon Lok LeiRichard D Wilkinson
Aug 18, 2017·The Journal of Physiology·Beatriz TrenorWayne Giles
Jun 9, 2017·Biomedical Engineering Online·Cunjin LuoHenggui Zhang
Oct 7, 2017·Frontiers in Physiology·Barbara WiśniowskaSebastian Polak
Feb 18, 2021·Pacing and Clinical Electrophysiology : PACE·Stefano PaganiAlfio Quarteroni

❮ Previous
Next ❯

Software Mentioned

preDiCT
CellML

Related Concepts

Related Feeds

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Cardiac Electrophysiology

Cardiac electrophysiology is the study of electrical activities of the heart and includes the assessment, diagnosis, and treatment of cardiac events. Find the latest research on cardiac electrophysiology here.