Incidence of primary graft dysfunction after lung transplantation is altered by timing of allograft implantation

Thorax. 2019 Apr;74(4):413-416. doi: 10.1136/thoraxjnl-2018-212021. Epub 2018 Oct 9.

Abstract

The importance of circadian factors in managing patients is poorly understood. We present two retrospective cohort studies showing that lungs reperfused between 4 and 8 AM have a higher incidence (OR 1.12; 95% CI 1.03 to 1.21; p=0.01) of primary graft dysfunction (PGD) in the first 72 hours after transplantation. Cooling of the donor lung, occurring during organ preservation, shifts the donor circadian clock causing desynchrony with the recipient. The clock protein REV-ERBα directly regulates PGD biomarkers explaining this circadian regulation while also allowing them to be manipulated with synthetic REV-ERB ligands.

Keywords: lung transplantation; macrophage biology.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Circadian Clocks / physiology*
  • Female
  • Humans
  • Lung Transplantation / methods*
  • Macrophages, Alveolar / metabolism
  • Male
  • Mice, Knockout
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / deficiency
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / physiology
  • Organ Preservation / methods
  • Primary Graft Dysfunction / etiology
  • Primary Graft Dysfunction / prevention & control*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Donors
  • Transplant Recipients

Substances

  • NR1D1 protein, human
  • Nr1d1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1