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• W2071960196 abstract "Abstract Aim: To perform an empirical, pharmacological, separation of early afterdepolarizations (EADs) and transmural gradients of repolarization in arrhythmogenesis in a genetically modified mouse heart modelling human long QT syndrome (LQT) 3. Methods: Left ventricular endocardial and epicardial monophasic action potentials and arrhythmogenic tendency were compared in isolated wild type (WT) and Scn5a +/Δ hearts perfused with 0.1 and 1 μ m propranolol and paced from the right ventricular epicardium. Results: All spontaneously beating bradycardic Scn5a +/Δ hearts displayed EADs, triggered beats and ventricular tachycardia (VT; n = 7), events never seen in WT hearts ( n = 5). Perfusion with 0.1 and 1 μ m propranolol suppressed all EADs, triggered beats and episodes of VT. In contrast, triggering of VT persisted following programmed electrical stimulation in 6 of 12 (50%), one of eight (12.5%), but six of eight (75%) Scn5a +/Δ hearts perfused with 0, 0.1 and 1 μ m propranolol respectively in parallel with corresponding alterations in repolarization gradients, reflected in action potential duration (ΔAPD 90 ) values. Thus 0.1 μ m propranolol reduced epicardial but not endocardial APD 90 from 54.7 ± 1.6 to 44.0 ± 2.0 ms, restoring ΔAPD 90 from −3.8 ± 1.6 to 3.5 ± 2.5 ms (all n = 5), close to WT values. However, 1 μ m propranolol increased epicardial APD 90 to 72.5 ± 1.2 ms and decreased endocardial APD 90 from 50.9 ± 1.0 to 24.5 ± 0.3 ms, increasing ΔAPD 90 to −48.0 ± 1.2 ms. Conclusion: These findings empirically implicate EADs in potentially initiating spontaneous arrhythmogenic phenomena and transmural repolarization gradients in the re‐entrant substrate that would sustain such activity when provoked by extrasystolic activity in murine hearts modelling human LQT3 syndrome." @default.
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• W2071960196 date "2007-09-26" @default.
• W2071960196 modified "2023-10-13" @default.
• W2071960196 title "Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in ΔKPQ Scn5a murine hearts modelling human long QT 3 syndrome" @default.
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• W2071960196 doi "https://doi.org/10.1111/j.1748-1716.2007.01770.x" @default.
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