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Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery

Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery
Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery

Background: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. Methods: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. Results: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased “cellular component morphogenesis” and a decrease in “blood circulation”. Lipidomic analysis did not identify any lipids significantly altered by either intervention. Discussion: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia.

Cardio-pulmonary bypass, Inflammation, Proteomics, Transcriptomics, Ventilation
0167-5273
40-47
Durham, A. L.
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Al Jaaly, E.
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Graham, R.
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Brook, P. O.
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Bae, J. H.
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Heesom, K. J.
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Postle, A. D.
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Lavender, P.
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Jazrawi, E.
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Reeves, B.
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Fiorentino, F.
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Mumby, S.
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Angelini, G. D.
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Adcock, I. M.
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Durham, A. L.
eee95155-ed42-4b81-bfeb-426fe19b649b
Al Jaaly, E.
977cc749-1089-40e5-9af5-67558f9ea892
Graham, R.
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Brook, P. O.
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Bae, J. H.
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Heesom, K. J.
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Postle, A. D.
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Lavender, P.
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Jazrawi, E.
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Reeves, B.
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Fiorentino, F.
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Mumby, S.
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Angelini, G. D.
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Adcock, I. M.
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Durham, A. L., Al Jaaly, E., Graham, R., Brook, P. O., Bae, J. H., Heesom, K. J., Postle, A. D., Lavender, P., Jazrawi, E., Reeves, B., Fiorentino, F., Mumby, S., Angelini, G. D. and Adcock, I. M. (2020) Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery. International Journal of Cardiology, 309, 40-47. (doi:10.1016/j.ijcard.2020.03.054).

Record type: Article

Abstract

Background: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. Methods: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. Results: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased “cellular component morphogenesis” and a decrease in “blood circulation”. Lipidomic analysis did not identify any lipids significantly altered by either intervention. Discussion: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia.

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More information

Accepted/In Press date: 20 March 2020
e-pub ahead of print date: 21 March 2020
Keywords: Cardio-pulmonary bypass, Inflammation, Proteomics, Transcriptomics, Ventilation

Identifiers

Local EPrints ID: 441829
URI: http://eprints.soton.ac.uk/id/eprint/441829
ISSN: 0167-5273
PURE UUID: b96f81e1-c763-4ad7-8c64-bc75f3fd602a
ORCID for A. D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

Catalogue record

Date deposited: 29 Jun 2020 16:33
Last modified: 26 Nov 2021 02:32

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Contributors

Author: A. L. Durham
Author: E. Al Jaaly
Author: R. Graham
Author: P. O. Brook
Author: J. H. Bae
Author: K. J. Heesom
Author: A. D. Postle ORCID iD
Author: P. Lavender
Author: E. Jazrawi
Author: B. Reeves
Author: F. Fiorentino
Author: S. Mumby
Author: G. D. Angelini
Author: I. M. Adcock

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