PMID- 28624975 OWN - NLM STAT- MEDLINE DCOM- 20180402 LR - 20181102 IS - 1435-1803 (Electronic) IS - 0300-8428 (Linking) VI - 112 IP - 4 DP - 2017 Jul TI - Deleterious acute and chronic effects of bradycardic right ventricular apex pacing: consequences for arrhythmic outcome. PG - 46 LID - 10.1007/s00395-017-0636-z [doi] AB - In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min. ECG, and left (LV) and right ventricular (RV) monophasic action potentials durations (MAPD) were recorded; activation time (AT) and activation recovery interval (ARI) were determined from ten distinct LV electrograms; interventricular mechanical delay (IVMD) and time-to-peak strain (TTP) of the LV septal and lateral wall (DeltaTTP: lateral wall minus septal wall) were obtained echocardiographically. Dofetilide (25 mug/kg/5 min) was infused to study TdP inducibility. In baseline AAVB, in comparison to SR, RVA bradypacing acutely increased QT interval, LV, and RVMAPD. Echocardiographic IVMD and DeltaTTP were initially increased, which was partially corrected after 3 weeks of RVA pacing (IVMD: 22 +/- 13 vs. 42 +/- 11 vs. 31 +/- 6 ms; DeltaTTP: -2 +/- 47 vs. -114 +/- 38 vs. -36 +/- 22 ms). QT interval (362 +/- 23 vs. 373 +/- 29 ms), LVMAPD (245 +/- 18 vs. 253 +/- 22 ms), RVMAPD (226 +/- 26 vs. 238 +/- 31 ms), and mean LV-ARI (268 +/- 5 vs. 267 +/- 6 ms) were not significantly changed after 3 weeks of RVA pacing. During AAVB, dofetilide increased mean LV-ARI (381 +/- 11 ms) with largest increases in the later activated basal areas (slope AT-ARI: +0.96). In contrast with acute RVA pacing, 3 week pacing increased TdP inducibility (0/13 vs. 11/21) and mean LV-ARI (484 +/- 18 ms), while the slope of AT-ARI responded differently on dofetilide (-2.37), with larger APD increases in the early region. The latter was supported at the molecular level: reduced RNA expressions of three repolarization-related ion channel genes in early (KCNQ1, KCNH2, and KCNJ2) versus two in late regions (KNCQ1 and KCNJ2). In conclusion, bradycardic RVA pacing acutely induced LV intra- and interventricular mechanical dyssynchrony, which was partially reversed after 3 weeks of pacing (remodeling). The latter occurred without apparent baseline electrical effects. However, dofetilide clearly unmasked (region-specific) arrhythmic consequences of remodeling. FAU - Stams, T R G AU - Stams TRG AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - Dunnink, A AU - Dunnink A AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - van Everdingen, W M AU - van Everdingen WM AD - Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Beekman, H D M AU - Beekman HDM AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - van der Nagel, R AU - van der Nagel R AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - Kok, B AU - Kok B AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - Bierhuizen, M F A AU - Bierhuizen MFA AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. FAU - Cramer, M J AU - Cramer MJ AD - Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Meine, M AU - Meine M AD - Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Vos, M A AU - Vos MA AD - Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM, Utrecht, The Netherlands. m.a.vos@umcutrecht.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170617 PL - Germany TA - Basic Res Cardiol JT - Basic research in cardiology JID - 0360342 SB - IM MH - Animals MH - Arrhythmias, Cardiac/*physiopathology MH - Bradycardia/*physiopathology MH - Cardiac Pacing, Artificial/*adverse effects MH - Dogs MH - Heart Ventricles/*physiopathology MH - Torsades de Pointes MH - Ventricular Remodeling/*physiology OTO - NOTNLM OT - Electrical dyssynchrony OT - Mechanical dyssynchrony OT - RV pacing OT - Torsade de pointes OT - Ventricular remodeling EDAT- 2017/06/19 06:00 MHDA- 2018/04/03 06:00 CRDT- 2017/06/19 06:00 PHST- 2015/12/03 00:00 [received] PHST- 2017/06/08 00:00 [accepted] PHST- 2017/06/19 06:00 [entrez] PHST- 2017/06/19 06:00 [pubmed] PHST- 2018/04/03 06:00 [medline] AID - 10.1007/s00395-017-0636-z [pii] AID - 10.1007/s00395-017-0636-z [doi] PST - ppublish SO - Basic Res Cardiol. 2017 Jul;112(4):46. doi: 10.1007/s00395-017-0636-z. Epub 2017 Jun 17.