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Ischemia reperfusion injury\u00a0(IRI) is a major challenge in the field as it can cause post-transplantation complications and limit the use of organs from extended criteria donors. Machine perfusion technology has the potential to mitigate IRI; however, it\u00a0currently fails to achieve its full potential due to a lack of highly sensitive and specific assays to assess organ quality during perfusion. We developed a real-time and non-invasive method of assessing organs during perfusion based on mitochondrial function and injury using resonance Raman spectroscopy. It uses a 441\u00a0nm laser and a high-resolution spectrometer to quantify the oxidation state of mitochondrial cytochromes during perfusion. This index of mitochondrial oxidation, or 3RMR, was used to understand differences in mitochondrial recovery of cold ischemic rodent livers during machine perfusion at normothermic temperatures with an acellular versus cellular perfusate. Measurement of the mitochondrial oxidation revealed that there was no difference in 3RMR of fresh livers as a function of normothermic perfusion when comparing acellular versus cellular-based perfusates. However, following 24\u00a0h of static cold storage, 3RMR returned to baseline faster with a cellular-based perfusate, yet 3RMR progressively increased during perfusion, indicating injury may develop over time. Thus, this study emphasizes the need for further refinement of a reoxygenation strategy during normothermic machine perfusion that considers cold ischemia durations, gradual recovery\/rewarming, and risk of hemolysis.<\/jats:p>","DOI":"10.1038\/s41598-024-57773-w","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T14:05:09Z","timestamp":1711548309000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Real-time monitoring of mitochondrial oxygenation during machine perfusion using resonance Raman spectroscopy predicts organ function"],"prefix":"10.1038","volume":"14","author":[{"given":"Rohil","family":"Jain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuella O.","family":"Ajenu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Lopera Higuita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab O. A.","family":"Hafiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alona","family":"Muzikansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic","family":"Romfh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon N.","family":"Tessier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"57773_CR1","unstructured":"Organ preservation: from the past to the future. Acta Pharmacologica Sinica. https:\/\/www.nature.com\/articles\/aps2017182."},{"key":"57773_CR2","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1002\/lt.26457","volume":"28","author":"TG Cotter","year":"2022","unstructured":"Cotter, T. G. et al. Preservation solutions for static cold storage in donation after circulatory death and donation after brain death liver transplantation in the United States. Liver Transpl. 28, 1454\u20131462 (2022).","journal-title":"Liver Transpl."},{"key":"57773_CR3","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/j.transproceed.2005.03.134","volume":"37","author":"JW Kupiec-Weglinski","year":"2005","unstructured":"Kupiec-Weglinski, J. W. & Busuttil, R. W. Ischemia and Reperfusion Injury in Liver Transplantation. Transplant. Proc. 37, 1653\u20131656 (2005).","journal-title":"Transplant. Proc."},{"key":"57773_CR4","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1111\/liv.14091","volume":"39","author":"WA Dar","year":"2019","unstructured":"Dar, W. A., Sullivan, E., Bynon, J. S., Eltzschig, H. & Ju, C. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. 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Dr. Tessier and Mr. Romfh have provisional patent applications relevant to this study. P.R. is an employee and shareholder of Pendar Technologies. S.N.T.\u2019s competing interests are managed by the MGH and Partners HealthCare in accordance with their conflict-of-interest policies, and P. R.\u2019s competing interests are subject to the Research Integrity Policy of Pendar Technologies. The following patented technologies have been used in this study: US2020\/0281474A1 In-vivo monitoring of cellular energetics with Raman spectroscopy (application). Additional patent applications for use in ophthalmology, tissue viability, and burn injury assessment using Resonance Raman Spectroscopy have been submitted where R.J. is also an inventor. This does not alter our adherence to Scientific Reports\u2019 policies on sharing data and materials. All other authors do not have competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7328"}}