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

Peter Cunningham; Robert Maidstone; Hannah Durrington; Rajamiyer Venkateswaran; Marcelo Cypel; Shaf Keshavjee; Julie Gibbs; Andrew Loudon; Chung Wai Chow; David Ray; John Blaikley

doi:10.1136/thoraxjnl-2018-212021

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

Peter Cunningham, Robert Maidstone, Hannah Durrington, Rajamiyer Venkateswaran, Marcelo Cypel, Shaf Keshavjee, Julie Gibbs, Andrew Loudon, Chung Wai Chow, David Ray, John Blaikley

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	413-416
Number of pages	4
Journal	Thorax
Volume	74
Issue number	4
Early online date	9 Oct 2018
DOIs	https://doi.org/10.1136/thoraxjnl-2018-212021
Publication status	Published - 9 Oct 2018

Keywords

lung transplantation
macrophage biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/thoraxjnl-2018-212021Licence: CC BY

Cite this

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title = "Incidence of Primary graft dysfunction after lung transplantation is altered by timing of allograft implantation",

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",

author = "Peter Cunningham and Robert Maidstone and Hannah Durrington and Rajamiyer Venkateswaran and Marcelo Cypel and Shaf Keshavjee and Julie Gibbs and Andrew Loudon and Chow, {Chung Wai} and David Ray and John Blaikley",

note = "Funding Information: 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. open access This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/. Publisher Copyright: {\textcopyright} 2019 Author(s) (or their employer(s)). Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

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doi = "10.1136/thoraxjnl-2018-212021",

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AU - Cunningham, Peter

AU - Maidstone, Robert

AU - Durrington, Hannah

AU - Venkateswaran, Rajamiyer

AU - Cypel, Marcelo

AU - Keshavjee, Shaf

AU - Gibbs, Julie

AU - Loudon, Andrew

AU - Chow, Chung Wai

AU - Ray, David

AU - Blaikley, John

N1 - Funding Information: 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. open access This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/. Publisher Copyright: © 2019 Author(s) (or their employer(s)). Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2018/10/9

Y1 - 2018/10/9

N2 - 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.

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

Abstract

Keywords

UN SDGs

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Investigation of REVERBalpha as a Therapeutic Target in Pulmonary Fibrosis.

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

Abstract

Keywords

UN SDGs

Access to Document

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Projects

Investigation of REVERBalpha as a Therapeutic Target in Pulmonary Fibrosis.

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