IndraLab

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Flecainide activates SCN5A. 13 / 13
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"Flecainide blocks the Nav1.5 channel in its inactivated state [ 8 ], therefore reducing the inward flow of sodium in the cell and slowing the physiological recovery of the Nav1.5 from the inactivated [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Flecainide increased the RTD in the LV and RV of Scn5a +/- hearts, while quinidine decreased it in both."
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"Fourthly, the pro- and anti-arrhythmic agents flecainide and quinidine both increased VERPs in both WT and Scn5a +/- hearts in all regions, although the effect was more pronounced with quinidine than flecainide (e.g. 39.9 +/-0.9 ms before drug to 45.3 +/-2.6 ms with flecainide and to 73.3 +/-1.5 ms with quinidine, p < 0.05, n = 6 for the RV in Scn5a +/-; Fig."
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"In contrast, they exerted more noticeable effects particularly in the RV of Scn5a +/- hearts, where the DeltaVERP was significantly increased (from 9.1 +/-1.1 to 21 +/-0.9 ms, p < 0.05, n = 6) by flecainide and significantly decreased (to 4.5 +/-0.5 ms, p < 0.05, n = 6) by quinidine."
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"However, flecainide prolonged APD (90) in WT but not Scn5a +/-, whereas quinidine prolonged APD (90) in both WT and Scn5a +/-."
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"Flecainide therefore causes premature conduction failure in the Scn5a +/- RV at higher pacing rates."
23836691
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"On the other hand, the conduction slowing in RyR2 S/S mice was quantitatively similar to that observed in heterozygous Na + channel Na v 1.5-subunit knock-out (SCN5A +/-) mice, or WT mice treated with flecainide, pointing to the possibility that drugs which further compromise CV or excitability may be even proarrhythmic."
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"However, at higher rates of 13.5 Hz, corresponding to exercising heart rates, flecainide treatment increased the magnitude of theta ' alternans specifically in the Scn5a +/- RV epicardium (from 0.00 (0.00) to 0.0051 (2.55) ms -1, P = 0.021)."
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"Our findings of heightened QT dispersion in Scn5a +/- hearts, further increased by flecainide but not by quinidine, directly parallel the respective pro- and antiarrhythmic effects of the 2 drugs experimentally and clinically."
20638671
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"Furthermore, recent studies have implicated increased repolarization gradients across the RV wall in the arrhythmogenic mechanism in Scn5a +/- mice, which are increased by flecainide but reduced by quinidine."
20638671
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"Flecainide increased the latencies in Scn5a +/- RV epicardium (from 24.59 (6.68) to 38.20 (18.94) ms; U = 21.0, P = 1.6 x 10 -4, r = 0.67)."
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"Conduction velocity restitution showed lower initial values and earlier points of failure during incremental pacing in the murine Scn5a +/- right ventricle (RV) epicardium particularly when treated with flecainide."
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"Flecainide treatment increased theta ' alternans in Scn5a +/- RV epicardium, in accord with the changes in maximum theta ' and conduction failure."
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