Evidence map›Paper›PMID 41214305›Full record

ArticleComprehensive Physiology2025

Pulmonary Vascular Endothelial Dysfunction Is Induced by Nonpulsatile Pulmonary Blood Flow in an Ovine Classic Glenn Model.

Jonathan Hyde, Michael A Smith, Naveen Swami, John H Hwang, Yenchun Chao, Jason Boehme, Gary W Raff, Casper Noah Nilsson, Wenhui Gong, Gail H Deutsch and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Comprehensive Physiology, 2025. 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

5 · Who and what money

Authors and funding

16 authors.

Jonathan HydeDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Michael A SmithDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.ORCID 0000-0002-7899-7248
Naveen SwamiDivision of Pediatric Cardiothoracic Surgery, Department of Surgery, University of California, San Francisco, California, USA.
John H HwangDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Yenchun ChaoDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Jason BoehmeDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.ORCID 0000-0003-4908-9934
Gary W RaffDivision of Pediatric Cardiothoracic Surgery, Department of Surgery, University of California, Davis, California, USA.
Casper Noah NilssonDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Wenhui GongDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Gail H DeutschDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Eric G JohnsonDepartment of Surgical and Radiological Sciences, From the University of California-Davis, School of Veterinary Medicine, Davis, Davis, California, USA.ORCID 0000-0002-3059-4052
Ting WangCenter of Translational Science, Florida International University, Port St. Lucie, Florida, USA.
Stephen M BlackCenter of Translational Science, Florida International University, Port St. Lucie, Florida, USA.
Sanjeev A DatarDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.
Emin MaltepeDivision of Neonatology, Department of Pediatrics, University of California, San Francisco, California, USA.
Jeffrey R FinemanDivision of Pediatric Critical Care, Department of Pediatrics, University of California, San Francisco, California, USA.ORCID 0000-0001-9740-405X

Funding

TGF-ß-SOX18-Collagen metabolism in pulmonary vascular disease associated with CHDP01HL146369 · NHLBI · UNIVERSITY OF ARIZONA · PI Stephen M Black · 2020 to 2026
$18.7M
Altered Lymphatic Function and Development in Congenital Heart DiseaseR01HL133034 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Sanjeev A. Datar · 2016 to 2026
$6.4M
Integrating Environmental Cues at the Maternal-Fetal Vascular InterfaceR01HD072455 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALTEPE, EMIN · 2012 to 2023
$4.3M
The Child Health Research Career Development Program at UCSFK12HD105250 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raphael Hirsch · 2021 to 2026
$2.5M
Multidisciplinary Research Training in Pediatric Pulmonary Vascular DiseaseT32HL160508 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Steven Herbert Abman, Eric Douglas Austin · 2022 to 2026
$1.7M
Mito-inflammation and sepsis-induced acute lung injuryR01HL175502 · NHLBI · FLORIDA INTERNATIONAL UNIVERSITY · PI Stephen M Black · 2025 to 2026
$1.4M
Pulmonary vascular glutamine metabolism at the intersection of hemodynamic forces and smooth muscle proliferation in congenital heart diseaseK08HL148512 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOEHME, JASON · 2020 to 2024
$874k
Additional Ventures P0583322Additional Ventures P0583323NHLBI NIH HHS K08 HL148512NHLBI NIH HHS P01 HL146369NHLBI NIH HHS R01 HL133034NHLBI NIH HHS R01 HL175502NHLBI NIH HHS T32 HL160508NICHD NIH HHS K12 HD105250NICHD NIH HHS R01 HD072455NIH HHS K08HL148512NIH HHS K12HD105250NIH HHS P01HL146369NIH HHS R01 HD072455NIH HHS R01HL133034NIH HHS T32HL160508
6 · The paper itself

Abstract

backgroundPulmonary vascular disease (PVD) in patients with single ventricular heart disease following the partial cavalpulmonary connection (Glenn) is a significant source of morbidity. However, the etiology of pulmonary vascular endothelial cell (EC) dysfunction, an established precursor to PVD, is incompletely understood but may involve abnormal blood flow patterns, hypoxemia, and polycythemia. HYPOTHESIS: Utilizing an ovine Glenn model, we hypothesized that nonpulsatile pulmonary blood flow (PBF) induces pulmonary vascular EC dysfunction, independent of hypoxemia or polycythemia.

methodsSeven lambs (6-8 weeks old) underwent a Glenn procedure. Eight weeks later, Glenn and age-matched controls were studied. The response to the endothelium-dependent vasodilator acetylcholine (Ach) was determined in isolated pulmonary arteries (PA). Nitric oxide (NO) and endothelin-1 (ET-1) signaling were determined in right lung tissues. Indices of cell proliferation, angiogenesis, and apoptosis were determined in PA endothelial cells (PAECs). Comparisons were made by unpaired t-test and ANOVA.

resultsThere were no differences in age, hemoglobin, or oxygen saturation between groups. Mean PA pressure and left PA flow were higher, and right lung blood flow was lower in Glenn lambs compared to controls (p < 0.05). All other baseline hemodynamics were similar. Glenn PAs had impaired relaxation to Ach. Glenn lung NO metabolite levels (NOx) and eNOS protein were lower, and ET-1 levels and prepro-ET-1 protein were higher than controls (p < 0.05). Glenn PAECs had higher rates of proliferation and angiogenesis, and decreased apoptosis (p < 0.05).

conclusionsThe initiation of nonpulsatile PBF following the Glenn induces early EC dysfunction independent of hypoxemia and polycythemia.

Indexed as

Endothelium, VascularPulmonary ArteryPulmonary CirculationAnimalsDisease Models, AnimalEndothelial CellsEndothelin-1Nitric OxideSheepEndothelin-1Nitric Oxidecongenital heart diseaseendothelial cellsendothelin‐1nitric oxidepulmonary hypertensionsingle ventricular heart disease

Identifiers

PMID41214305
PMCPMC12602377

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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.