Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-κB

Scott D. Ross, Irving L. Kron, James J. Gangemi, Kimberly S. Shockey, Mark Stoler, John A. Kern, Curtis G. Tribble, Victor E. Laubach

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

A central role for nuclear factor-κB (NF-κB) in the induction of lung inflammatory injury is emerging. We hypothesized that NF-κB is a critical early regulator of the inflammatory response in lung ischemia-reperfusion injury, and inhibition of NF-κB activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantation model, left lungs were harvested and stored in cold Euro-Collins preservation solution for 6 h before transplantation. Activation of NF-κB occurred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, given to the lung graft during organ preservation (40 mmol/1) effectively inhibited NF-κB activation and significantly improved lung function. Compared with control lungs 4 h after transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower PCO2, reduced mean pulmonary arterial pressure, and reduced edema and cellular infiltration. These results demonstrate that NF-κB is rapidly activated and is associated with poor pulmonary graft function in transplant reperfusion injury, and targeting of NF-κB may be a promising therapy to reduce this injury and improve lung function.

Original languageEnglish (US)
Pages (from-to)L528-L536
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number3 23-3
DOIs
StatePublished - 2000

Keywords

  • Ischemia
  • Organ preservation
  • Pyrrolidine dithiocarbamate

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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