Evidence map›Paper›PMID 23703113›Full record

ArticleJournal of applied physiology (Bethesda, Md. : 1985)2013

Endocardial endothelium is a key determinant of force-frequency relationship in rat ventricular myocardium.

Xiaoxu Shen, Zhen Tan, Xin Zhong, Ye Tian, Xian Wang, Bo Yu, Genaro Ramirez-Correa, Anne Murphy, Kathleen Gabrielson, Nazareno Paolocci and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of applied physiology (Bethesda, Md. : 1985), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension.Journal of the American Heart Association · 2023
    Article
  5. Article
  6. Review
  7. Article
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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

11 authors at 4 institutions in 2 countries.

Xiaoxu ShenCardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Zhen Tan
Xin Zhong
Ye Tian
Xian Wang
Bo Yu
Genaro Ramirez-Correa
Anne Murphy
Kathleen Gabrielson
Nazareno Paolocci
Wei Dong Gao
Harbin Medical University · CNJohns Hopkins Medicine · USDongzhimen Hospital Affiliated to Beijing University of Chinese Medicine · CNJohns Hopkins University · US

Funding

MOLECULAR PHYSIOLOGY OF MYOCARDIAL TROPONIN I VARIANTSR01HL063038 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MURPHY, ANNE M · 1999 to 2018
$6.2M
Mechanisms Underlying Mitrochondrial Dysfunction in the Diabetic HeartR01HL091923 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI AKAR, FADI GABRIEL, AON, MIGUEL ANTONIO · 2009 to 2012
$1.9M
Molecular Physiology of Myocardial Troponin I VariantsR56HL063038 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MURPHY, ANNE M · 2008 to 2008
$500k
Request for Zeiss LSM 510 MP Multiphoton Imaging SystemS10RR024550 · NCRR · JOHNS HOPKINS UNIVERSITY · PI KUO, SCOT CHARLES · 2008 to 2008
$500k
NCRR NIH HHS S10 RR024550NHLBI NIH HHS HL091923NHLBI NIH HHS HL63038NHLBI NIH HHS R01 HL063038
6 · The paper itself

Abstract

We tested the hypothesis that removing endocardial endothelium (EE) negatively impacts the force-frequency relationship (FFR) of ventricular myocardium and dissected the signaling that underlies this phenomenon. EE of rat trabeculae was selectively damaged by brief (<1 s) exposure to 0.1% Triton X-100. Force, intracellular Ca(2+) transient (iCa(2+)), and activity of protein kinase A (PKA) and protein kinase C (PKC) were determined. In control muscles, force and iCa(2+) increased as the stimulation frequency increased in steps of 0.5 Hz up to 3.0 Hz. However, EE-denuded (EED) muscles exhibited a markedly blunted FFR. Neither isoproterenol (ISO; 0.1-5 nmol/l) nor endothelin-1 (ET-1; 10-100 nmol/l) alone restored the slope of FFR in EED muscles. Intriguingly, however, a positive FFR was restored in EED preparations by combining low concentrations of ISO (0.1 nmol/l) and ET-1 (20 nmol/l). In intact muscles, PKA and PKC activity increased proportionally with the increase in frequency. This effect was completely lost in EED muscles. Again, combining ISO and ET-1 fully restored the frequency-dependent rise in PKA and PKC activity in EED muscles. In conclusion, selective damage of EE leads to significantly blunted FFR. A combination of low concentrations of ISO and ET-1 successfully restores FFR in EED muscles. The interdependence of ISO and ET-1 in this process indicates cross-talk between the β1-PKA and ET-1-PKC pathways for a normal (positive) FFR. The results also imply that dysfunction of EE and/or EE-myocyte coupling may contribute to flat (or even negative) FFR in heart failure.

Indexed as

Action PotentialsAnimalsCalciumCalcium SignalingCardiotonic AgentsCyclic AMP-Dependent Protein KinasesElectric StimulationEndothelin-1Endothelium, VascularExcitation Contraction CouplingHeartHeart RateHeart VentriclesIn Vitro TechniquesIsoproterenolMyocardial ContractionCalciumCardiotonic AgentsCyclic AMP-Dependent Protein KinasesEndothelin-1IsoproterenolProtein Kinase Ccardiac excitation-contraction couplingendocardial endotheliumendothelin-1force-frequency relationshipisoproterenolrat myocardium

Identifiers

PMID23703113
PMCPMC3743009
OpenAlexW2000728605

What OpenQuestion holds

Textmetadata
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.