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Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates
Published on: October 18, 2018
[Arrhythmogenic effects of non cardiovascular drugs]
1Service de cardiologie B, hôpital Arnaud de Villeneuve, CHU, Montpellier. jm-davy@chu-montpellier.fr
Abstract:
Among the unwanted effects of drugs, arrhythmogenic effects are particularly fearsome. Although rare they are serious, and responsible for syncope or sudden death, often linked with torsades de pointe on established long QT. For non cardiovascular drugs, detection is difficult because patients do not undergo systematic cardiological surveillance. Nevertheless understanding the risk, identification of predisposing factors, and consideration of the contra-indications are the rules of prescription, which are even more indispensable when the pathology being treated is benign. In effect, the implicated drugs are mainly anti-histamines, antibiotics, neuroleptics and antidepressants. The pharmaceutical companies, regulatory agencies, and pharmacological surveillance services must recognise the greatest possible risk of a drug, thanks to pre-clinical data, experimental electrophysiology both in vivo (measurement of the QT interval) and in vitro (action potential duration) or even in the elementary channel (essentially analysis of the iKr current). Correlated with clinical data (QT changes, pharmacokinetic interactions), a risk/benefit profile can therefore be established, which is even more demanding when the pathology is benign or when alternative drugs are available.
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