Evidence map›Paper›PMID 38752959›Full record

ArticleJACC. Clinical electrophysiology2024

Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.

Kenneth R Laurita, Joseph S Piktel, Laken Irish, Michelle Nassal, Aurelia Cheng, Matthew McCauley, Gary Pawlowski, Adrienne T Dennis, Yi Suen, Soufian Almahameed and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Clinical electrophysiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Review
  3. The electrophysiology of ventricular cell pairs.Pflugers Archiv : European journal of physiology · 2025
    Review
  4. Review
  5. 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

13 authors.

Kenneth R LauritaHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address: kenneth.laurita@case.edu.
Joseph S PiktelHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA; Department of Emergency Medicine, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Laken IrishHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Michelle NassalHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Aurelia ChengDepartment of Emergency Medicine, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Matthew McCauleyDepartment of Emergency Medicine, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Gary PawlowskiHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Adrienne T DennisHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Yi SuenHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA; Department of Emergency Medicine, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Soufian AlmahameedHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Ohad ZivHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
Robert G GourdieFralin Biomedical Research Institute, Virginia Tech University, Roanoke, Virginia, USA.
Lance D WilsonHeart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA; Department of Emergency Medicine, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.

Funding

Connexin-based Signaling in the Heart: Cellular and ExosomalR35HL161237 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI ROBERT G GOURDIE · 2022 to 2026
$4.4M
Novel mechanisms and treatment of arrhythmia during resuscitationR01HL142754 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI KENNETH LAURITA, Lance D Wilson · 2020 to 2026
$3.4M
The Role of the Sodium Channel Beta Subunit in Cardiac ConductionR01HL141855 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI GOURDIE, ROBERT G, POELZING, STEVEN · 2018 to 2021
$1.8M
Novel mechanisms and treatment of arrhythmia during resuscitationR56HL142754 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI LAURITA, KENNETH, WILSON, LANCE D · 2018 to 2018
$603k
NHLBI NIH HHS R01 HL141855NHLBI NIH HHS R01 HL142754NHLBI NIH HHS R35 HL161237NHLBI NIH HHS R56 HL142754
6 · The paper itself

Abstract

backgroundVentricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown.

objectivesThis study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity.

methodsWe used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations.

resultsIn vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution.

conclusionsThese results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.

Indexed as

Connexin 43Gap JunctionsTachycardia, VentricularVentricular FibrillationAction PotentialsAnimalsDisease Models, AnimalFemaleHeart ArrestMaleOligopeptidesSwineConnexin 43Oligopeptidesrotigaptidecardiac alternansconnexin 43gap junctionresuscitationsudden cardiac arrestventricular fibrillation/tachycardia

Identifiers

PMID38752959
PMCPMC11525958

What OpenQuestion holds

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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.