Tissue-Based Assay Development

Purkinje Fibers

Purkinje fibers (PFs) are critical for assuring the appropriate timing and sequence of ventricular contraction. They rapidly conduct and distribute impulses throughout the ventricles, initiating synchronous apical-to-basal ejection of blood from both ventricular chambers cyclically. It is well appreciated that a polymorphic ventricular tachycardia, Torsades de Pointes (TdP), occurring with acquired and congenital long QT syndromes is associated with the generation of long action potential duration (APD)-related early after depolarizations (EADs) and EAD-induced triggered activity. EADs, occurring as oscillations during phase 2 or 3 of the action potential (AP) are potentially arrhythmogenic. PFs are more sensitive to drug-induced long APD and EADs than working ventricular muscle, and consequently, EADs are more easily induced in PFs.

In agreement with these observations in vitro, in vivo studies show that the initiation of EAD-induced TdP arises in PFs. Therefore, Purkinje fibers appear to play a particularly important role as a generator of EADs in TdP arrhythmias associated with long QT syndromes. Consequently, the cardiac Purkinje fiber is a well established preparation commonly used in the pharmaceutical industry to evaluate the cardiac electrophysiological effects of drugs known to prolong QT interval. The sensitivity of in vitro preparations to compounds which affect cardiac repolarization may depend on the species, gender, as well as on the nature of the preparation. The physiologically relevant whole-ventricle Purkinje fibers preparation where Purkinje fibers are connected to the surrounding ventricular tissue is a common preparation to assess drug effects on APD.