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SUMMARY:Uncertainty in the prediction of drug-induced arrhythmogenic risk 
 assessed by a multi-dimensional hazard map - Seiryo Sugiura (University of
  Tokyo)
DTSTART:20190606T153000Z
DTEND:20190606T160000Z
UID:TALK125638@talks.cam.ac.uk
CONTACT:INI IT
DESCRIPTION:Arrhythmogenicity   of drugs involves multi-scale events takin
 g place at molecular\, cellular\,   tissue and organ levels. In order to u
 nderstand the mechanism behind this   complex phenomena\, we developed a m
 ulti-scale 3D heart simulator\, with which   we can evaluate the arrhythmo
 genicity of drugs based on their inhibitory   actions on multiple ionic cu
 rrents. Recently\, we extended this approach to   create a hazard map of d
 rug-induced arrhythmia identifying the region at risk   in a multi-dimensi
 onal space\, each co-ordinate of which represents the   inhibition of spec
 ific ionic current. This hazard map can also be used to   assess the two m
 ajor uncertainties we encounter in the evaluation of   arrhythmogenic risk
 . One is the uncertainty in experimentally determining the   inhibitory ac
 tion of drugs on ionic currents. The other is the individual   variability
  in the sensitivity to drugs possibly caused by the polymorphism   in gene
 s coding ion channels or enzymes responsible for the drug metabolism.   Th
 ese uncertainties can also be identified by a region of drug effects in   
 this hazard map and the distance from its border to the region at risk can
  be   taken to indicate the safety margin.
LOCATION:Seminar Room 1\, Newton Institute
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