Abstract 15870: Ventricular Arrhythmias Evoked by Tefluthrin, a Pyrethroid, at Longer Pacing Cycle Lengths in Mice Hearts
Introduction: We have previously demonstrated an increase in heart rate by a voltage-gated sodium current (INa) activator, (-)-epicatechin-3-gallate, without provoking early after-depolarization (EAD) due to it accelerating INa recovery kinetics. However, our recent preliminary data showed that tefluthrin (Tef), a pyrethroid with INa-activating property, increased the ventricular action potential duration (APD) and ventricular tachycardia (VT) inducibility.
Hypothesis: To differentiate between the two different INa agonists, we hypothesize that the frequency of activation modulated by the INa agonist is a critical factor for the inducibility of VT.
Methods: We evaluated the effects of Tef on both the bioelectrical activities in Langendorff-perfused intact mice hearts by optical mapping techniques and the INa recovery in isolated cardiomyocytes by whole-cell patch-clamp configuration.
Results: INa was enhanced by Tef in a concentration-dependent manner with EC50 of 0.97 μM. Unlike (-)-epicatechin-3-gallate, Tef (1 μM) decelerated INa recovery from inactivation via prolong the time constant (τ) from 14.7±1.9 to 25.8±2.4 ms (n=8, p<0.05, panel A). At 130 and 150 ms pacing cycle length (PCL, panel B) pacing, Tef (1 μM) not only prolonged APD at 80% (APD80) but also evoked EADs which contributed to premature ventricular contraction (PVC) and VT in intact mice hearts. At 100 ms PCL, the APD80 prolongation was not significantly altered. Neither PVCs nor VTs were observed at the shorter PCL.
Conclusions: Tef-induced ventricular arrhythmias at longer PCL is associated with a decrease in INa recovery kinetics but can be restored by pacing at shorter PCL.
- Ventricular arrhythmia
- Sodium channel
- Cellular Electrophysiology
- Arrhythmia mapping
- Ventricular tachycardia
Author Disclosures: A.Z. Wu: None. D. Yin: None. Z. Xu: None. T.H. Everett: None. Z. Chen: None. S. Wu: None.
- © 2016 by American Heart Association, Inc.