Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

Thom R G Stams; Peter Oosterhoff; Atty Heijdel; Albert Dunnink; Jet D M  Beekman; Roel van der Nagel; Harold V. M.  van Rijen; Marcel A.G.  van der Heyden; Marc A. Vos

doi:10.1253/circj.CJ-15-1335

Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

Thom R G Stams, Peter Oosterhoff, Atty Heijdel, Albert Dunnink, Jet D M Beekman, Roel van der Nagel, Harold V. M. van Rijen, Marcel A.G. van der Heyden^*, Marc A. Vos

^*Corresponding author for this work

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Abstract

Background: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.Methods and Results: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, P

Original language	English
Pages (from-to)	1336-1345
Number of pages	10
Journal	Circulation journal
Volume	80
Issue number	6
DOIs	https://doi.org/10.1253/circj.CJ-15-1335
Publication status	Published - 2016

Keywords

Electrical remodeling
Preload
Short-term variability of repolarization
Stretch
Torsade de Pointes

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Stams, T. R. G., Oosterhoff, P., Heijdel, A., Dunnink, A., Beekman, J. D. M., van der Nagel, R., van Rijen, H. V. M., van der Heyden, M. A. G., & Vos, M. A. (2016). Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs. Circulation journal, 80(6), 1336-1345. https://doi.org/10.1253/circj.CJ-15-1335

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title = "Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs",

abstract = "Background: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.Methods and Results: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, P",

keywords = "Electrical remodeling, Preload, Short-term variability of repolarization, Stretch, Torsade de Pointes",

author = "Stams, {Thom R G} and Peter Oosterhoff and Atty Heijdel and Albert Dunnink and Beekman, {Jet D M} and {van der Nagel}, Roel and {van Rijen}, {Harold V. M.} and {van der Heyden}, {Marcel A.G.} and Vos, {Marc A.}",

year = "2016",

doi = "10.1253/circj.CJ-15-1335",

language = "English",

volume = "80",

pages = "1336--1345",

journal = "Circulation journal",

issn = "1346-9843",

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T1 - Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

AU - Stams, Thom R G

AU - Oosterhoff, Peter

AU - Heijdel, Atty

AU - Dunnink, Albert

AU - Beekman, Jet D M

AU - van der Nagel, Roel

AU - van Rijen, Harold V. M.

AU - van der Heyden, Marcel A.G.

AU - Vos, Marc A.

PY - 2016

Y1 - 2016

N2 - Background: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.Methods and Results: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, P

AB - Background: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.Methods and Results: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, P

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KW - Preload

KW - Short-term variability of repolarization

KW - Stretch

KW - Torsade de Pointes

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Beat-to-beat variability in preload unmasks latent risk of Torsade de Pointes in anesthetized chronic atrioventricular block dogs

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