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Metabolomic fingerprinting of porcine lung tissue during pre-clinical prolonged ex vivo lung perfusion using in vivo SPME coupled with LC-HRMS

查看全文 作  者:Nikita [1]Looby;Anna [1,2]Roszkowska;Aadil [3]Ali;Barbara [4]Bojko;Marcelo [3]Cypel;Janusz [1]Pawliszyn 高影响力作者 机构地区:[1]Department of Chemistry,University of Waterloo,Waterloo,N2L 3G1,Canada;[2]Department of Pharmaceutical Chemistry,Medical University of Gdansk,80-416,Gdansk,Poland;[3]Division of Thoracic Surgery,University Health Network,Toronto,M5G 2C4,Canada;[4]Department of Pharmacodynamics and Molecular Pharmacology,Faculty of Pharmacy,Collegium Medicum in Bydgoszcz,Nicolaus Copernicus University in Torun,85-089,Bydgoszcz,Poland高影响力机构 出  处:《Journal of Pharmaceutical Analysis》索引2022年第12卷第4期,共11页高影响力期刊 基  金:the Canadian Institute of Health Research(CIHR)-Natural Sciences and Engineering Research Council(NSERC)of the Canada Collaborative Health Research Projects program for their financial support(Grant No.:355935)the Natural Sciences and Engineering Research Council of Canada Industrial Research Chair(IRC)program. 摘  要:Normothermic ex vivo lung perfusion(NEVLP)has emerged as a modernized organ preservation technique that allows for detailed assessment of donor lung function prior to transplantation.The main goal of this study was to identify potential biomarkers of lung function and/or injury during a prolonged(19 h)NEVLP procedure using in vivo solid-phase microextraction(SPME)technology followed by liquid chromatography-high resolution mass spectrometry(LC-HRMS).The use of minimally invasive in vivo SPME fibers for repeated sampling of biological tissue permits the monitoring and evaluation of biochemical changes and alterations in the metabolomic profile of the lung.These in vivo SPME fibers were directly introduced into the lung and were also used to extract metabolites(on-site SPME)from fresh perfusate samples collected alongside lung samplings.A subsequent goal of the study was to assess the feasibility of SPME as an in vivo method in metabolomics studies,in comparison to the traditional inlab metabolomics workflow.Several upregulated biochemical pathways involved in pro-and antiinflammatory responses,as well as lipid metabolism,were observed during extended lung perfusion,especially between the 11th and 12th hours of the procedure,in both lung and perfusate samples.However,several unstable and/or short-lived metabolites,such as neuroprostanes,have been extracted from lung tissue in vivo using SPME fibers.On-site monitoring of the metabolomic profiles of both lung tissues through in vivo SPME and perfusate samples on site throughout the prolonged NEVLP procedure can be effectively performed using in vivo SPME technology. 关 键 词:Normothermic ex vivo lung perfusion Solid phase microextraction Lung metabolomics
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