Evidence map›Paper›PMID 40043942›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2025

Targeted immunotherapy with sphingosine-1-phosphate improves myocardial contractility and mitochondrial function in a novel murine ex vivo perfusion and transplantation model.

John Iguidbashian, Jack Zakrzewski, Li Lu, Anastacia M Garcia, Ludmila Khailova, Xinsheng Deng, Robert Plenter, Francisco G La Rosa, Stephanie Nakano, Kevin Lynch and 3 more

Abstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

John IguidbashianDivision of General Surgery, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, Colo.
Jack ZakrzewskiDivision of General Surgery, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, Colo.
Li LuDivision of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Colorado, Anschutz Medical Campus, Aurora, Colo.
Anastacia M GarciaDivision of Cardiology, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo.
Ludmila KhailovaDivision of Cardiology, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo.
Xinsheng DengDivision of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Colorado, Anschutz Medical Campus, Aurora, Colo.
Robert PlenterDivision of Cardiology, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo.
Francisco G La RosaDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colo.
Stephanie NakanoDivision of Cardiology, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo.
Kevin LynchDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, Va.
James JaggersDivision of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Colorado, Anschutz Medical Campus, Aurora, Colo.
Jesse DavidsonDivision of Cardiology, Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo.
Matthew L StoneDivision of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Colorado, Anschutz Medical Campus, Aurora, Colo. Electronic address: Matthew.Stone@childrenscolorado.org.

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI JANINE A HIGGINS · 1995 to 2026
$32.6M
NRSA Training CoreTL1TR002533 · NCATS · UNIVERSITY OF COLORADO DENVER · PI CICUTTO, LISA · 2018 to 2022
$3.0M
Colorado StARR Program in Medicine and Pediatrics (CSPMP)R38HL143511 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Steven Herbert Abman, Peter N. Buttrick · 2020 to 2026
$2.7M
CTSA Predoctoral T32 at University of Colorado DenverT32TR004367 · NCATS · UNIVERSITY OF COLORADO DENVER · PI Lisa Cicutto · 2023 to 2026
$1.5M
NCATS NIH HHS T32 TR004367NCATS NIH HHS TL1 TR002533NHLBI NIH HHS R38 HL143511NIDDK NIH HHS P30 DK048520
6 · The paper itself

Abstract

objectiveTo develop a reproducible ex vivo heart perfusion (EVHP) and murine heart transplantation model and to evaluate the efficacy of hypothermic, acellular ex vivo perfusion with sphingosine-1-phosphate (S1P) as a strategy to mitigate transplantation-associated ischemia-reperfusion injury (IRI).

methodsDonor hearts from wild-type mice were stratified by preservation technique. Group 1 hearts (n = 4) served as nontransplanted controls. Group 2 hearts (n = 10) underwent 90 minutes of cold static preservation (CSP) following cardioplegic arrest in donor mice. Group 3 to 5 hearts (n = 10/group) underwent EVHP with hypothermic acellular solution (Krebs-Henseleit buffer [KH]) alone (group 3), with KH plus S1P (FTY-720) (group 4), or with KH plus S1P plus S1P receptor subtype 2 antagonist (JTE-013) (group 5). Group 2 to 5 hearts were then transplanted into recipient mice with 120 minutes of reperfusion. Hearts were evaluated for function by echocardiography, for histopathologic injury by neutrophil infiltration, and for mitochondrial bioenergetics by Seahorse bioanalysis.

resultsFunctional assessment demonstrated comparable post-transplantation allograft function as defined by fractional shortening (FS) and fractional area change (FAC) for CSP and KH-only EVHP mice (P > .05). EVHP with S1P improved post-transplantation function by both FS and FAC (P < .05). Coadministration of S1P with S1PR2 antagonist abrogated the functional improvement of S1P alone (P < .05). EVHP with S1P also reduced injury severity scores based on neutrophil infiltration (P < .05). Finally, EVHP with S1P transplanted hearts demonstrated improved mitochondrial function compared to hearts transplanted after standard CSP (P < .05).

conclusionsDonor hearts perfused with hypothermic acellular perfusate and S1P demonstrated improved post-transplantation heart function, decreased histologic injury, and increased mitochondrial performance compared to hearts preserved with cold-static CSP, representing a potential strategy to mitigate IRI occurring in heart transplantation.

Indexed as

Heart TransplantationLysophospholipidsMitochondria, HeartMyocardial ContractionMyocardial Reperfusion InjuryPerfusionSphingosineAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLSphingosine 1 Phosphate Receptor ModulatorsSphingosine-1-Phosphate ReceptorsLysophospholipidsSphingosinesphingosine 1-phosphateSphingosine 1 Phosphate Receptor ModulatorsSphingosine-1-Phosphate Receptorsex vivo heart perfusionheart transplantationischemia reperfusion injurymurine heart transplantationsphingosine

Identifiers

PMID40043942
PMCPMC12768582

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.