Evidence map›Paper›PMID 38678474›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2024

Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model.

Raymond J Strobel, Huy Q Ta, Andrew M Young, Alex M Wisniewski, Anthony V Norman, Evan P Rotar, Mark H Stoler, Irving L Kron, Swapnil K Sonkusare, Mark E Roeser and 1 more

Abstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Raymond J StrobelDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Huy Q TaDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Andrew M YoungDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Alex M WisniewskiDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Anthony V NormanDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Evan P RotarDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Mark H StolerDepartment of Pathology, University of Virginia School of Medicine, Charlottesville, Va.
Irving L KronDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Swapnil K SonkusareRobert M. Berne Cardiovascular Research Center and the Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Va.
Mark E RoeserDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va.
Victor E LaubachDepartment of Surgery, University of Virginia School of Medicine, Charlottesville, Va. Electronic address: laubach@virginia.edu.

Funding

Cardiovascular Surgery Training ProgramT32HL007849 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KRON, IRVING L., LAUBACH, VICTOR E · 1998 to 2025
$7.0M
Flow-Activated Calcium Signaling Microdomains in Small Pulmonary ArteriesR01HL146914 · NHLBI · UNIVERSITY OF VIRGINIA · PI Swapnil K. Sonkusare · 2019 to 2026
$3.8M
Role of TRPV4 channel signaling in lung ischemia-reperfusion injuryR01HL157407 · NHLBI · UNIVERSITY OF VIRGINIA · PI LAUBACH, VICTOR E, SONKUSARE, SWAPNIL K. · 2021 to 2024
$2.7M
Targeted treatment of acute lung injury using isolated lung perfusionR01HL168041 · NHLBI · UNIVERSITY OF VIRGINIA · PI Irving L. Kron, Victor E Laubach · 2024 to 2026
$2.4M
NHLBI NIH HHS R01 HL146914NHLBI NIH HHS R01 HL157407NHLBI NIH HHS R01 HL168041NHLBI NIH HHS T32 HL007849
6 · The paper itself

Abstract

objectiveTransient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model.

methodsA porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared.

resultsAfter transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function.

conclusionsTreatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant.

Indexed as

Lung TransplantationReperfusion InjuryTRPV Cation ChannelsAnimalsDisease Models, AnimalLungPiperidinesQuinolinesSwineGSK2193874PiperidinesQuinolinesTRPV Cation Channelsendothelial barrierinflammationischemia-reperfusion injurylung transplantationprimary graft dysfunctionTRPV4 channel

Identifiers

PMID38678474
PMCPMC11416340

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Registered trials

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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.