title: Mechanisms underlying arrhythmogenesis in long QT syndrome.
abstract: Long QT syndrome is a disease of delayed ventricular repolarization. It manifests clinically as recurrent syncope and sudden cardiac death caused by an atypical form of polymorphic ventricular tachycardia known as torsades de pointes (TdP). Evidence obtained from the studies using the rabbit left and right ventricular wedge preparations indicates that the development of TdP is relying not only on the genesis of an R-on-T trigger, but also on the formation of a functional reentrant substrate. When ventricular endocardial or subendocardial repolarization is prolonged either because of gene mutations or by drugs that reduce the net repolarization current, cell membrane potential fluctuates during phase 2 of the action potential phase 2 because of reactivation of L-type calcium current, that is, the appearance of phase 2 early afterdepolarization (EAD). In the rabbit left ventricular wedge, QT prolongation and EAD due to pure IKr inhibition are accompanied by a disproportional increase in transmural dispersion of repolarization (TDR). Early afterdepolarization in endocardium or subendocardium is able to produce new action potentials in cells with a relatively short action potential duration (eg, ventricular epicardium) probably via an electrotonic effect when TDR is large enough. This, in turn, results in an R-on-T extrasystole that is capable of initiating TdP. Enhanced TDR is essential not only for the genesis of the first initiating beat of TdP by facilitating the propagation of EAD, but also for the maintenance of TdP by serving as a functional reentrant substrate.
authors.affiliation: Main Line Health Heart Center, Wynnewood, PA 19096, USA.
authors.forename: Ramarao S
authors.initials: RS
authors.lastname: Lankipalli
authors.forename: Tiangang
authors.initials: T
authors.lastname: Zhu
authors.forename: Donling
authors.initials: D
authors.lastname: Guo
authors.forename: Gan-Xin
authors.initials: GX
authors.lastname: Yan
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D015220:Calcium Channels / Q000378:metabolism; D004699:Endocardium / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels