ArticleJCI insight2018
Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The trial behind it
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- Mitigating sepsis-induced vascular endothelial dysfunction through Niban phosphorylation.Vascular medicine (London, England) · 2026Article
- Histidine-rich glycoprotein ameliorated lung ischemia-reperfusion injury in a mouse model.JHLT open · 2026Article
- Targeting the proline-glycine-proline-protease feed-forward loop attenuates primary graft dysfunction after lung transplantation.Frontiers in immunology · 2026Article
- Lung Ischemia-Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?Antioxidants (Basel, Switzerland) · 2025Review
- Mechanisms of lung crosstalk with end organs: scientific session V-ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Primary Graft Dysfunction in Lung Transplantation: An Overview of the Molecular Mechanisms.International journal of molecular sciences · 2025Review
- Oxidation of low-density lipoprotein by hemoglobin causes pulmonary microvascular endothelial barrier dysfunction through lectin-like oxidized LDL receptor 1.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Signs of Hemolysis Predict Mortality and Ventilator Associated Pneumonia in Severe Acute Respiratory Distress Syndrome Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation.ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2025Article
- Association between acetaminophen use and 30-day mortality in critically ill patients with pulmonary embolism: a retrospective cohort study using the MIMIC-IV database.Frontiers in pharmacology · 2025Article
- Matrix metalloproteinase-7 is dispensable in a mouse model of sepsis-induced acute lung injury.PloS one · 2025Article
- Neutrophil reduction attenuates the severity of lung injury in the early phase of pneumococcal pneumonia in mice.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Risk factors and clinical consequences of early extubation failure in lung transplant recipients.JHLT open · 2024Article
- Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.Annals of intensive care · 2024Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Vitamin C: Rationale for Its Use in Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS).Antioxidants (Basel, Switzerland) · 2024Review
- Advances and Applications of Lung Organoids in the Research on Acute Respiratory Distress Syndrome (ARDS).Journal of clinical medicine · 2024Review
- Mitigating the risk of inflammatory type primary graft dysfunction by applying an integrated approach to assess, modify and match risk factors in lung transplantation.Frontiers in transplantation · 2024Article
- A Split-LungTransplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Liraglutide pretreatment attenuates sepsis-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
Corrections and comments
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Authors and funding
26 authors at 11 institutions in 2 countries.
Funding
Abstract
Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing lung microvascular permeability and tested this in patients, ex vivo human lungs, and cultured human lung microvascular endothelial cells. In a nested case control study of 40 patients with severe PGD at 72 hours and 80 matched controls without PGD, elevated preoperative CFH was independently associated with increased PGD risk (odds ratio [OR] 2.75, 95%CI, 1.23-6.16, P = 0.014). The effect of CFH on PGD was magnified by reperfusion fraction of inspired oxygen (FiO2) ≥ 0.40 (OR 3.41, P = 0.031). Isolated perfused human lungs exposed to intravascular CFH (100 mg/dl) developed increased vascular permeability as measured by lung weight (CFH 14.4% vs. control 0.65%, P = 0.047) and extravasation of Evans blue-labeled albumin dye (EBD) into the airspace (P = 0.027). CFH (1 mg/dl) also increased paracellular permeability of human pulmonary microvascular endothelial cell monolayers (hPMVECs). Hyperoxia (FiO2 = 0.95) increased human lung and hPMVEC permeability compared with normoxia (FiO2 = 0.21). Treatment with acetaminophen (15 μg/ml), a specific hemoprotein reductant, prevented CFH-dependent permeability in human lungs (P = 0.046) and hPMVECs (P = 0.037). In summary, CFH may mediate PGD through oxidative effects on microvascular permeability, which are augmented by hyperoxia and abrogated by acetaminophen.
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Registered trials
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.