Article Text
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.
- lung transplantation
- macrophage biology
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Footnotes
Contributors JFB, ASL and DWR: conceived the study. JFB, PSC, HJD and JEG: performed the experiments. SK, MC, RVV, JFB and C-WC: designed analysis of the patient cohort. RM: performed analysis of the patient cohort. All authors contributed to the writing and critical appraisal of the manuscript.
Funding JB holds a MRC clinician scientist award (MR/L006499/1). DWR and AL both hold Wellcome Trust investigator awards (107851/Z/15/Z). JG has an Arthritis Research Career Development Fellowship (Reference 20629) and HD is supported by an Asthma UK Senior Clinical Academic Development Award (AUK-SCAD-2013-229).
Competing interests None declared.
Ethics approval University Healthcare Network and South Manchester REC.
Provenance and peer review Not commissioned; externally peer reviewed.