scholarly journals Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia‐induced‐cardiomyopathy

2020 ◽  
Author(s):  
Ryo Yonai ◽  
Mihoko Kawabata ◽  
Shingo Maeda ◽  
Tomoyuki Kawashima ◽  
Yasuhide Tsuda ◽  
...  
Keyword(s):  
Torsade De Pointes ◽  
Amiodarone Therapy ◽  
Dispersion Of Repolarization ◽  
Transmural Dispersion Of Repolarization ◽  
Intravenous Amiodarone ◽  
Transmural Dispersion ◽  
Tachycardia Induced Cardiomyopathy

Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na+ current in the heart

2009 ◽  
Vol 297 (3) ◽  
pp. H1048-H1057 ◽  
Author(s):  
Lin Wu ◽  
Sridharan Rajamani ◽  
Hong Li ◽  
Craig T. January ◽  
John C. Shryock ◽  
...  
Keyword(s):  
Torsade De Pointes ◽  
Polymorphic Ventricular Tachycardia ◽  
Isolated Hearts ◽  
T Wave ◽  
Dispersion Of Repolarization ◽  
Transmural Dispersion Of Repolarization ◽  
Repolarization Reserve ◽  
Monophasic Action Potentials ◽  
Transmural Dispersion

Reduction of repolarization reserve increases the risk of arrhythmia. We hypothesized that inhibition of K+ current ( IK) to decrease repolarization reserve would unmask the proarrhythmic role of endogenous, physiological late Na+ current (late INa). Monophasic action potentials (MAP) and 12-lead electrocardiogram were recorded from female rabbit isolated hearts. To block IK and reduce repolarization reserve, E-4031, 4-aminopyridine, and BaCl2 were used; to block endogenous late INa, tetrodotoxin (TTX) and ranolazine were used. E-4031 (1–60 nM) concentration-dependently prolonged MAP duration (MAPD90) and increased duration of the T wave from Tpeak to Tend (Tpeak-Tend), transmural dispersion of repolarization (TDR), and beat-to-beat variability (BVR) of MAPD90. E-4031 caused spontaneous and pause-triggered polymorphic ventricular tachycardia [ torsade de pointes (TdP)]. In the presence of 60 nM E-4031, TTX (0.6–3 μM) and ranolazine (5–10 μM) shortened MAPD90, decreased TDR, BVR, and Tpeak-Tend ( n = 9–20, P < 0.01), and abolished episodes of TdP. In hearts treated with BaCl2 or 4-aminopyridine plus E-4031, TTX (0.6–3 μM) shortened MAPD90 and decreased Tpeak-Tend. Ranolazine could not reverse the effect of E-4031 to inhibit human ether-a-go-go-related gene (HERG) K+ current; thus, the reversal by ranolazine of effects of E-4031 was likely due to inhibition of late INa and not to antagonism of the HERG-blocking action of E-4031. We conclude that endogenous, physiological late INa contributes to arrhythmogenesis in hearts with reduced repolarization reserve. Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by IK inhibitors.

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