Skip to main content

Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.

Publication ,  Journal Article
Shaver, CM; Wickersham, N; McNeil, JB; Nagata, H; Miller, A; Landstreet, SR; Kuck, JL; Diamond, JM; Lederer, DJ; Kawut, SM; Palmer, SM ...
Published in: JCI Insight
January 25, 2018

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 25, 2018

Volume

3

Issue

2

Location

United States

Related Subject Headings

  • Primary Graft Dysfunction
  • Oxidative Stress
  • Middle Aged
  • Microvessels
  • Male
  • Lung Transplantation
  • Lung
  • Hyperoxia
  • Humans
  • Hemoglobins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shaver, C. M., Wickersham, N., McNeil, J. B., Nagata, H., Miller, A., Landstreet, S. R., … Lung Transplant Outcomes Group (LTOG), . (2018). Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury. JCI Insight, 3(2). https://doi.org/10.1172/jci.insight.98546
Shaver, Ciara M., Nancy Wickersham, J Brennan McNeil, Hiromasa Nagata, Adam Miller, Stuart R. Landstreet, Jamie L. Kuck, et al. “Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.JCI Insight 3, no. 2 (January 25, 2018). https://doi.org/10.1172/jci.insight.98546.
Shaver CM, Wickersham N, McNeil JB, Nagata H, Miller A, Landstreet SR, et al. Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury. JCI Insight. 2018 Jan 25;3(2).
Shaver, Ciara M., et al. “Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.JCI Insight, vol. 3, no. 2, Jan. 2018. Pubmed, doi:10.1172/jci.insight.98546.
Shaver CM, Wickersham N, McNeil JB, Nagata H, Miller A, Landstreet SR, Kuck JL, Diamond JM, Lederer DJ, Kawut SM, Palmer SM, Wille KM, Weinacker A, Lama VN, Crespo MM, Orens JB, Shah PD, Hage CA, Cantu E, Porteous MK, Dhillon G, McDyer J, Bastarache JA, Christie JD, Ware LB, Lung Transplant Outcomes Group (LTOG). Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury. JCI Insight. 2018 Jan 25;3(2).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 25, 2018

Volume

3

Issue

2

Location

United States

Related Subject Headings

  • Primary Graft Dysfunction
  • Oxidative Stress
  • Middle Aged
  • Microvessels
  • Male
  • Lung Transplantation
  • Lung
  • Hyperoxia
  • Humans
  • Hemoglobins