February 12, 2018

Protecting transplanted lungs

Acetaminophen may offer a simple treatment to prevent tissue injury following lung transplant, Vanderbilt researchers have discovered.

Primary graft dysfunction (PGD) — acute lung injury that develops within 72 hours of lung transplantation — is a major cause of illness and death after transplant. The mechanisms leading to PGD are not well understood, and there are no specific therapeutic interventions.

Ciara Shaver, MD, PhD, Lorraine Ware, MD, and colleagues, explored the role of cell-free hemoglobin (normally located inside red blood cells) in PGD.

The investigators found that elevated preoperative cell-free hemoglobin was associated with increased risk of PGD in lung transplant patients. In isolated human lungs and cultures of pulmonary endothelial cells (the cells that line blood vessels), they showed that cell-free hemoglobin increased vascular permeability, or “leakiness.”

Treatment with acetaminophen, a drug that counters the oxidizing action of hemoglobin, prevented the increased permeability in isolated lungs and cultured cells.

The findings, reported in JCI Insight, suggest that cell-free hemoglobin contributes to PGD by increasing vascular permeability and that acetaminophen may be a novel treatment to prevent PGD.

This research was supported by the National Institutes of Health (grants HL135849, HL103836, HL087115, HL126176, HL126671, HL117676, HL121406, HL136888), Vanderbilt Faculty Research Scholars, American Thoracic Society, and the Parker B. Francis Family Foundation.

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