Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-PO06 - Poster Session VI (ID 26) Poster

D-PO06-017 - Proarrhythmic Remodeling In The Chronic AV Block Dog Model Is Controlled By The Degree Of Intraventricular Dyssynchrony Caused By Altered Ventricular Activation (ID 643)

Abstract

Background: Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, which promotes proarrhythmic electrical remodeling in the chronic AV block (CAVB) dog model.
Objective: We studied the arrhythmogenic and electromechanical outcome of different degrees of AVA.
Methods: Following AV block, AVA was established: idioventricular rhythm (IVR; n = 34), right ventricular apex paced animals (RVA; n = 12) or biventricular paced animals (CRT; n = 10). After 3 - 5 weeks of bradycardic remodeling, Torsade de Pointes arrhythmia (TdP) inducibility (definition: ≥3 TdP in 10 minutes) was tested with specific IKr-blocker Dofetilide (25 μg/kg/5 min). In RVA and CRT, MD was assessed by echocardiography as time to peak (TTP) LV septum- free wall (ΔTTP), while electrical intraventicular dyssynchrony (ΔARI) was determined using activation recovery interval (ARI) from 10 distinct left ventricular (LV) electrograms and calculated as dofetilide induced ARI prolongation of LV apex - free wall.
Results: Significantly more IVR animals became TdP inducible (24/31 IVR vs 5/12 RVA and 2/10 CRT, both p<0.05 vs IVR). In IVR, the focus is inconsistent and arising from 3 different predilected sites, excluding quantification of dyssynchrony. Intraventricular MD was significantly higher in RVA (ΔTTP: -83 ± 106 vs 8 ± 31 ms in CRT p<0.05).Dofetilide prolonged ARI more in the early activated regions, this intraventricular heterogeneity in prolongation was greater in RVA (ΔARI: 35 ± 62 vs -15 ± 19 ms in CRT, both p<0.05).
Conclusion: Severity of intraventricular MD affects the extent of electrical remodeling and proarrhythmic outcome in the CAVB dog model.
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