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Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs
- Source :
- Circulation journal, 80(6), 1336. Japanese Circulation Society
- Publication Year :
- 2016
-
Abstract
- Beat-to-beat variability in ventricular repolarization (BVR) associates with increased arrhythmic risk. Proarrhythmic remodeling in the dog with chronic AV-block (CAVB) compromises repolarization reserve and associates with increased BVR, which further increases upon dofetilide infusion and correlates with Torsade de Pointes (TdP) arrhythmias. It was hypothesized that these pro-arrhythmia-associated increases in BVR are induced by beat-to-beat variability in preload.Left ventricular monophasic action potential duration (LVMAPD) was recorded in acute (AAVB) and CAVB dogs, before and after dofetilide infusion. BVR was quantified as short-term variability of LVMAPD. The PQ-interval was controlled by pacing: either a constant or an alternating preload pattern was established, verified by PV-loop. The effect of the stretch-activated channel blocker, streptomycin, on BVR was evaluated in a second CAVB group. At alternating preload only, BVR was increased after proarrhythmic remodeling (0.45±0.14 ms AAVB vs. 2.2±1.1 ms CAVB, P0.01). At CAVB, but not at AAVB, dofetilide induced significant proarrhythmia. Preload variability augmented the dofetilide-induced BVR increase at CAVB (+1.5±0.8 ms vs. +0.9±0.9 ms, P=0.058). In the second group, the increase in baseline BVR by alternating preload (0.3±0.03 ms to 1.0±0.8 ms, P0.01) was abolished by streptomycin (0.5±0.2 ms, P0.05).In CAVB dogs, the inverse relation between BVR and repolarization reserve originates from an augmented sensitivity of ventricular repolarization to beat-to-beat preload changes. Stretch-activated channels appear to be involved in the mechanism of BVR. (Circ J 2016; 80: 1336-1345).
- Subjects :
- Risk
0301 basic medicine
Ventricular Repolarization
medicine.medical_specialty
Action Potentials
Beat (acoustics)
Dofetilide
030204 cardiovascular system & hematology
Preload
03 medical and health sciences
Dogs
0302 clinical medicine
Torsades de Pointes
Internal medicine
Phenethylamines
Journal Article
Animals
Medicine
Anesthesia
Channel blocker
Repolarization reserve
Atrioventricular Block
Sulfonamides
Stretch
business.industry
Arrhythmias, Cardiac
General Medicine
Short-term variability of repolarization
medicine.disease
Electrical remodeling
030104 developmental biology
Torsade de Pointes
Streptomycin
Cardiology
cardiovascular system
Action potential duration
business
Cardiology and Cardiovascular Medicine
Atrioventricular block
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 13469843
- Database :
- OpenAIRE
- Journal :
- Circulation journal, 80(6), 1336. Japanese Circulation Society
- Accession number :
- edsair.doi.dedup.....1302cb20872dd805ca188e1afb45d705