Why the study?
Do test compounds induce early or delayed afterdepolarizations in isolated Purkinje fibers?
Do test compounds induce early or delayed afterdepolarizations in isolated Purkinje fibers?
Isolated Purkinje fibers serve as an in vitro model to assess the risk of drug-induced arrhythmias such as torsades de pointes.
Isolated Purkinje fiber assays aid preclinical proarrhythmic screening; hypothesis-generating and should not yet change practice.
The proarrhythmic potential of new chemical entities can be investigated using in vitro electrophysiological techniques measuring the cardiac action potential in isolated Purkinje fibers. Different types of arrhythmias may occur as early afterdepolarizations (EADs), which are favored by action potential duration lengthening and bradycardia, or as delayed afterdepolarizations (DADs), which are facilitated by tachycardia. The effects of a test compound on the occurrence of these arrhythmias, thought to be responsible for the development of torsades de pointes in the clinic can be studied using the experimental protocols described in this unit.
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Picard et al. (2006) studied this question.
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