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Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.
- Source :
-
JCI insight [JCI Insight] 2018 Jan 25; Vol. 3 (2). Date of Electronic Publication: 2018 Jan 25 (Print Publication: 2018). - Publication Year :
- 2018
-
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.
- Subjects :
- Acetaminophen pharmacology
Allografts blood supply
Allografts immunology
Allografts pathology
Capillary Permeability drug effects
Capillary Permeability immunology
Case-Control Studies
Cell Line
Endothelial Cells metabolism
Endothelial Cells pathology
Female
Hemoglobins antagonists & inhibitors
Humans
Hyperoxia blood
Hyperoxia pathology
Lung blood supply
Lung cytology
Lung immunology
Lung pathology
Male
Microvessels cytology
Microvessels metabolism
Middle Aged
Oxidative Stress immunology
Primary Graft Dysfunction blood
Primary Graft Dysfunction pathology
Hemoglobins immunology
Hyperoxia immunology
Lung Transplantation adverse effects
Primary Graft Dysfunction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 3
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 29367464
- Full Text :
- https://doi.org/10.1172/jci.insight.98546