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

Author:

Cunningham Peter S,Maidstone Robert,Durrington Hannah JORCID,Venkateswaran Rajamayier V,Cypel Marcelo,Keshavjee Shaf,Gibbs Julie E,Loudon Andrew S,Chow Chung-Wai,Ray David W,Blaikley John F

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.

Funder

Arthritis Research UK

Wellcome Trust

Medical Research Council

Asthma UK

Publisher

BMJ

Subject

Pulmonary and Respiratory Medicine

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