Dynamic Changes and Roles of Specialized Pro-resolving Lipid Meditators in the Initiation and Resolution Process of Lung Ischemia-Reperfusion Injury in Rats

H. Oda¹, S. Tanaka¹, M. Shinohara², Y. Morimura¹, Y. Yokoyama¹, H. Kayawake¹, Y. Yamada¹, A. Ohsumi¹, D. Nakajima¹, H. Date¹

¹Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto City, Japan, ²The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe City, Japan

Meeting: 2022 American Transplant Congress

Abstract number: 674

Keywords: Ischemia, Lung, Lung transplantation, Perfusion

Topic: Basic Science » Basic Science » 14 - Ischemia Reperfusion

Session Information

Session Name: Ischemia Reperfusion

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Lung ischemia-reperfusion injury (IRI) is one of the significant complications after lung transplantation, which is a form of acute lung injury by robust inflammation. Specialized pro-resolving lipid mediators (SPMs) have been reported to have a critical role in the resolution of inflammation; however, little is known about the roles of SPMs in the initiation and resolution phase of lung IRI. We aimed to evaluate the dynamic changes of endogenous SPMs during the initiation and resolution of lung IRI and to determine the effects of SPM supplementation on lung IRI.

*Methods: We used a rat left hilar clamp model with 90 minutes of ischemia, followed by various reperfusion period (from 1 hour to 7 days). Dynamic changes in endogenous SPMs were evaluated with lipid mediator lipidomics using liquid chromatography-tandem mass spectrometry. For exogenous supplementation, aspirin-triggered (AT) resolvin D1 (AT-RvD1) or AT-lipoxin A₄ (AT-LXA₄) was administered immediately after reperfusion and the rats were sacrificed 3 hours after reperfusion for evaluation.

*Results: Endogenous SPMs in the left lung showed a decreasing trend after 1 hour of reperfusion. Oxygenation, neutrophil infiltration, and inflammatory cytokine levels (IL-1β and IL-6) improved 7 days following reperfusion; however, the level of endogenous SPMs remained low compared with that in the naïve lung in spite of the increasing trend of precursors of SPMs. Administration of AT-RvD1 and AT-LXA₄ significantly improved lung function, attenuated lung edema, decreased neutrophil infiltration, and reduced inflammatory cytokine levels 3 hours after reperfusion (each P < 0.05).

*Conclusions: Lipid mediator lipidomics revealed that the level of intrapulmonary endogenous SPMs decreased immediately after reperfusion and remained low after the recovery of lung function. Administration of AT-RvD1 or AT-LXA₄ prevented the exacerbation of lung IRI. The role of lipid mediators in the resolution phase of lung IRI needs further investigation.

To cite this abstract in AMA style:

Oda H, Tanaka S, Shinohara M, Morimura Y, Yokoyama Y, Kayawake H, Yamada Y, Ohsumi A, Nakajima D, Date H. Dynamic Changes and Roles of Specialized Pro-resolving Lipid Meditators in the Initiation and Resolution Process of Lung Ischemia-Reperfusion Injury in Rats [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/dynamic-changes-and-roles-of-specialized-pro-resolving-lipid-meditators-in-the-initiation-and-resolution-process-of-lung-ischemia-reperfusion-injury-in-rats/. Accessed November 21, 2024.

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