Evidence map›Paper›PMID 23948344›Full record

ArticleHeart rhythm2013

Transmural IK(ATP) heterogeneity as a determinant of activation rate gradient during early ventricular fibrillation: mechanistic insights from rabbit ventricular models.

Patrick M Boyle, Stéphane Massé, Kumaraswamy Nanthakumar, Edward J Vigmond

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Heart rhythm, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Early somatic mosaicism is a rare cause of long-QT syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  10. Article
  11. Review
  12. Review
  13. KATP Channels in the Cardiovascular System.Physiological reviews · 2016
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Advances in modeling ventricular arrhythmias: from mechanisms to the clinic.Wiley interdisciplinary reviews. Systems biology and medicine
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 3 countries.

Patrick M BoyleUniversity of Calgary, Calgary, Alberta, Canada; Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address: pmjboyle@jhu.edu.
Stéphane Massé
Kumaraswamy Nanthakumar
Edward J Vigmond
University Health Network · CAElectrophysiology and Heart Modeling Institute · FRJohns Hopkins University · US

Funding

Multi-scale Modeling of Calcium Mediated Triggered Activity in the HeartR01HL101196 · NHLBI · CALIFORNIA STATE UNIVERSITY NORTHRIDGE · PI SHIFERAW, YOHANNES · 2010 to 2013
$1.2M
NHLBI NIH HHS R01 HL101196NHLBI NIH HHS R01HL101196
6 · The paper itself

Abstract

backgroundActivation rate (AR) gradients develop during ventricular fibrillation (VF), with the highest AR on the surface near Purkinje system (PS) terminals (endocardium in humans and rabbits and epicardium in pigs). The application of glibenclamide to block adenosine triphosphate (ATP)-sensitive potassium current (IK(ATP)) before VF induction eliminates transmural AR gradients and prevents the induction of sustained arrhythmia. It remains unclear whether the PS, which is resistant to ischemia, is also a factor in AR heterogeneity.

objectiveTo dissect IK(ATP) and PS contributions to AR gradients during VF by using detailed computer simulations.

methodsWe constructed rabbit ventricular models with either subendocardial or subepicardial PS terminals. Physiologically relevant IK(ATP) gradients were implemented, and early VF was induced and observed.

resultsProminent AR gradients were observed only in models with large IK(ATP) gradients. The critical underlying factor of AR gradient maintenance was refractoriness in low-IK(ATP) regions, which blocked the propagation of action potentials from high-IK(ATP) regions. The PS played no role in transmural AR gradient maintenance, but did cause local spatial heterogeneity of AR on the surface adjacent to terminals. Simulated glibenclamide application during VF led to spontaneous arrhythmia termination within a few seconds in most cases, which builds on previous experimental findings of anti-VF properties of glibenclamide pretreatment.

conclusionDifferential IK(ATP) across the ventricular wall is an important factor underlying AR gradients during VF; thus, higher epicardial AR in pigs is most likely due to an abundance of epicardial IK(ATP). For terminating early VF, our results suggest that IK(ATP) modulation is a stronger target than Purkinje ablation.

Indexed as

Action PotentialsAnimalsElectrocardiographyHeart Conduction SystemHeart RateHeart VentriclesKATP ChannelsRabbitsVentricular FibrillationKATP Channelsaction potential durationactivation rateActivation rateactivation rate gradientadenosine triphosphateAPDARATPATP-sensitive potassium currentECGelectrocardiogramextracellular potassium concentrationf(ATP)fraction of channels in the active stateI(K(ATP))[K(+)](e)PMJPSPurkinje-myocardial junctionPurkinje systemtransmembrane voltageTransmural heterogeneityventricular fibrillationVentricular fibrillationVFV(m)ΔAR

Identifiers

PMID23948344
PMCPMC3826179
OpenAlexW2032710327

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.