Evidence map›Paper›PMID 39719415›Full record

ArticleJournal of the American Heart Association2025

Sequence-Dependent Repolarization Is Modulated by Endogenous Action Potential Duration Gradients Rather Than Electrical Coupling in Ventricular Myocardium.

Grace A Blair, Madeline Depman, William P Adams, Rowan O Maisonneuve, Gregory S Hoeker, Seth H Weinberg, Steve Poelzing

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. A Case Report: Electrotonic Modulation-Related T-Wave Over-Sensing After Left Bundle Branch Pacing.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Grace A BlairGraduate Program in Translational Biology Medicine and Health, Virginia Tech Roanoke VA USA.ORCID 0000-0002-5633-5497
Madeline DepmanGraduate Program in Translational Biology Medicine and Health, Virginia Tech Roanoke VA USA.
William P AdamsCenter for Vascular and Heart Research Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA USA.ORCID 0000-0002-5601-663X
Rowan O MaisonneuveCenter for Vascular and Heart Research Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA USA.
Gregory S HoekerCenter for Vascular and Heart Research Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA USA.ORCID 0000-0002-3917-4791
Seth H WeinbergDepartment of Biomedical Engineering Davis Heart and Lung Research Institute, The Ohio State University Columbus OH USA.ORCID 0000-0003-1170-0419
Steve PoelzingGraduate Program in Translational Biology Medicine and Health, Virginia Tech Roanoke VA USA.ORCID 0000-0002-6979-1264

Funding

Role of the Extracellular Space as a Modulator of the Cardiac Gap Junction - Conduction Velocity RelationshipR01HL102298 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI POELZING, STEVEN · 2011 to 2020
$3.9M
Arrhythmia Mechanisms Modulated by Intercalated Disc Extracellular NanodomainsR01HL159097 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Steven Poelzing · 2023 to 2026
$2.5M
Therapeutic Targeting of Voltage Gated Sodium Channel AutoregulationR01HL169610 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Steven Poelzing, Seth Howard Weinberg · 2024 to 2026
$2.1M
Unmasking Conduction Deficits in the Scn5a+/- Mouse Model of Brugada SyndromeF31HL160172 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI BONSON, GRACE ANNA · 2021 to 2022
$80k
NHLBI NIH HHS F31 HL160172NHLBI NIH HHS R01 HL102298NHLBI NIH HHS R01 HL159097NHLBI NIH HHS R01 HL169610
6 · The paper itself

Abstract

backgroundPrevious studies suggest the relationship between activation time (AT) and action potential duration (APD) in the heart is dependent on electrotonic coupling, but this has not been directly tested. This study assessed whether acute changes in electrical coupling, or other determinants of conduction or repolarization, modulate APD heterogeneity. METHODS AND

resultsLangendorff-perfused guinea pig hearts were epicardially paced and optically mapped after treatment with the gap junction uncoupler carbenoxolone, ephaptic uncoupler mannitol, ephaptic enhancer dextran 2MDa, sodium channel inhibitor flecainide, or rapid component of the delayed rectifier potassium channel inhibitor E4031. SD of APD and the AT-APD slope and coefficient of determination were quantified as metrics of APD heterogeneity. SD of APD increased with carbenoxolone, mannitol, and altered activation sequence. The AT-APD slope was insensitive to carbenoxolone, mannitol, dextran, flecainide, or E4031 but changed in response to activation sequence. The coefficient of determination did not change with carbenoxolone; decreased with mannitol, E4031, and activation sequence; but increased with dextran and flecainide. APD heterogeneity changes were dependent on whether the estimation used SD of APD or the AT-APD relationship. The pacing stimulus increased APD at the site of stimulation, revealing a confounding stimulus effect on APD within the measurement area. Simulations predict that the stimulus artifact and endogenous APD gradients are stronger determinants of APD heterogeneity than AT.

conclusionsAPD dependence on conduction is relatively small. Furthermore, APD heterogeneity within a mapping field of view is dependent on endogenous gradients, the stimulus artifact, and the experimental approach, rather than electrical coupling.

Indexed as

Action PotentialsCarbenoxoloneFlecainideAnimalsCardiac Pacing, ArtificialDextransGap JunctionsGuinea PigsHeart Conduction SystemHeart VentriclesIsolated Heart PreparationMaleMannitolPyridinium CompoundsSodium Channel BlockersTime Factors1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaineCarbenoxoloneDextransFlecainideMannitolPyridinium CompoundsSodium Channel Blockersbasic science researchcongenital heart diseaseelectrophysiologytranslational studies

Identifiers

PMID39719415
PMCPMC12054505

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.