Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome : Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall Export

@article{citeulike:1923629, abstract = {Background--This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. Methods and Results--Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 {micro}mol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 {micro}mol/L but shortened them at 30 {micro}mol/L. Unlike dl-sotalol, azimilide (>3 {micro}mol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 {micro}mol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. Conclusions--This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.}, author = {Yan, Gan-Xin and Wu, Ying and Liu, Tengxian and Wang, Jixin and Marinchak, Roger A. and Kowey, Peter R.}, citeulike-article-id = {1923629}, citeulike-linkout-0 = {http://circ.ahajournals.org/cgi/content/abstract/103/23/2851}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11401944}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11401944}, day = {12}, journal = {Circulation}, keywords = {arrhythmia}, month = {June}, number = {23}, pages = {2851--2856}, posted-at = {2007-11-15 18:59:01}, priority = {5}, title = {Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome : Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall}, url = {http://circ.ahajournals.org/cgi/content/abstract/103/23/2851}, volume = {103}, year = {2001} }

TY - JOUR ID - citeulike:1923629 L3 - citeulike-article-id:1923629 N2 - Background--This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. Methods and Results--Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 {micro}mol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 {micro}mol/L but shortened them at 30 {micro}mol/L. Unlike dl-sotalol, azimilide (>3 {micro}mol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 {micro}mol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. Conclusions--This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation. IS - 23 JF - Circulation EP - 2856 TI - Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome : Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall VL - 103 SP - 2851 KW - arrhythmia AU - Yan, Gan-Xin AU - Wu, Ying AU - Liu, Tengxian AU - Wang, Jixin AU - Marinchak, Roger AU - Kowey, Peter PY - 2001/06/12/ UR - http://circ.ahajournals.org/cgi/content/abstract/103/23/2851 ER -