Evidence map›Paper›PMID 29609890›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2018

Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion.

J Hunter Mehaffey, Eric J Charles, Adishesh K Narahari, Sarah Schubert, Victor E Laubach, Nicholas R Teman, Kevin R Lynch, Irving L Kron, Ashish K Sharma

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Ex-vivo lung perfusion therapies: do they add value to organ donation?Current opinion in organ transplantation · 2022
    Review
  7. Review
  8. Review
  9. Article
  10. Early Graft Dysfunction after Lung Transplantation.Current pulmonology reports · 2018
    Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

J Hunter MehaffeyDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Eric J CharlesDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Adishesh K NarahariDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Sarah SchubertDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Victor E LaubachDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Nicholas R TemanDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Kevin R LynchDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, Va.
Irving L KronDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Ashish K SharmaDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va. Electronic address: sharma@virginia.edu.
University of Virginia · US

Funding

TRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2M
Cardiovascular Surgery Training ProgramT32HL007849 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KRON, IRVING L., LAUBACH, VICTOR E · 1998 to 2025
$7.0M
Network for Cardiothoracic Surgical Investigations in Cardiovascular MedicineUM1HL088925 · NHLBI · UNIVERSITY OF VIRGINIA · PI BADHWAR, VINAY, KRON, IRVING L. · 2013 to 2025
$6.8M
Ex vivo perfusion in a lung box for rehabilitation of donor lungsR01HL119218 · NHLBI · UNIVERSITY OF VIRGINIA · PI KRON, IRVING L., LAUBACH, VICTOR E · 2013 to 2017
$3.3M
MD-PHAR Controlling sphingosine 1-phosphate synthesis and traffickingR01GM121075 · NIGMS · UNIVERSITY OF VIRGINIA · PI LYNCH, KEVIN R., SANTOS, WEBSTER L · 2016 to 2020
$2.1M
NHLBI NIH HHS R01 HL119218NHLBI NIH HHS T32 HL007849NHLBI NIH HHS UM1 HL088925NIGMS NIH HHS R01 GM121075NIGMS NIH HHS T32 GM007055
6 · The paper itself

Abstract

backgroundSphingosine-1-phosphate regulates endothelial barrier integrity and promotes cell survival and proliferation. We hypothesized that upregulation of sphingosine-1-phosphate during ex vivo lung perfusion would attenuate acute lung injury and improve graft function.

methodsC57BL/6 mice (n = 4-8/group) were euthanized, followed by 1 hour of warm ischemia and 1 hour of cold preservation in a model of donation after cardiac death. Subsequently, mice underwent 1 hour of ex vivo lung perfusion with 1 of 4 different perfusion solutions: Steen solution (Steen, control arm), Steen with added sphingosine-1-phosphate (Steen + sphingosine-1-phosphate), Steen plus a selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or Steen plus both additives (Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor). During ex vivo lung perfusion, lung compliance and pulmonary artery pressure were continuously measured. Pulmonary vascular permeability was assessed with injection of Evans Blue dye.

resultsThe combination of 1 hour of warm ischemia, followed by 1 hour of cold ischemia created significant lung injury compared with lungs that were immediately harvested after circulatory death and put on ex vivo lung perfusion. Addition of sphingosine-1-phosphate or sphingosine kinase inhibitor alone did not significantly improve lung function during ex vivo lung perfusion compared with Steen without additives. However, group Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor resulted in significantly increased compliance (110% ± 13.9% vs 57.7% ± 6.6%, P < .0001) and decreased pulmonary vascular permeability (33.1 ± 11.9 μg/g vs 75.8 ± 11.4 μg/g tissue, P = .04) compared with Steen alone.

conclusionsTargeted drug therapy with a combination of sphingosine-1-phosphate + sphingosine kinase inhibitor during ex vivo lung perfusion improves lung function in a murine donation after cardiac death model. Elevation of circulating sphingosine-1-phosphate via specific pharmacologic modalities during ex vivo lung perfusion may provide endothelial protection in marginal donor lungs leading to successful lung rehabilitation for transplantation.

Indexed as

Acute Lung InjuryAnimalsDeathDisease Models, AnimalLungLung TransplantationLysophospholipidsMiceMice, Inbred C57BLOrgan Preservation SolutionsPerfusionProtective AgentsSphingosineWarm IschemiaLysophospholipidsOrgan Preservation SolutionsProtective AgentsSphingosinesphingosine 1-phosphateex vivo lung perfusionischemia–reperfusion injurylung rehabilitationlung transplantationsphingosine

Identifiers

PMID29609890
PMCPMC6056006
OpenAlexW2794078245

What OpenQuestion holds

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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.