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2021;16 (10): e0258833.

Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion.

Reinier J de Vries, Stephanie E J Cronin, Padraic Romfh, Casie A Pendexter, Rohil Jain, Benjamin T Wilks, Siavash Raigani, Thomas M van Gulik, Peili Chen, Heidi Yeh, Korkut Uygun, Shannon N Tessier
Author Information
  1. Reinier J de Vries: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America.
  2. Stephanie E J Cronin: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America.
  3. Padraic Romfh: Pendar Technologies, Cambridge, MA, United States of America.
  4. Casie A Pendexter: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America. ORCID
  5. Rohil Jain: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America.
  6. Benjamin T Wilks: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America. ORCID
  7. Siavash Raigani: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America. ORCID
  8. Thomas M van Gulik: Department of Surgery, Amsterdam University Medical Centers-Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
  9. Peili Chen: Pendar Technologies, Cambridge, MA, United States of America.
  10. Heidi Yeh: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States of America.
  11. Korkut Uygun: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America.
  12. Shannon N Tessier: Center for Engineering in Medicine and Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, United States of America. ORCID
PMID: 34705828 DOI: 10.1371/journal.pone.0258833

Abstract

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

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Grants

  1. R01 DK107875/NIDDK NIH HHS
  2. R01 HL157803/NHLBI NIH HHS
  3. R01 DK096075/NIDDK NIH HHS
  4. R43 DK120127/NIDDK NIH HHS
  5. R00 HL143149/NHLBI NIH HHS
  6. R01 DK114506/NIDDK NIH HHS

MeSH Term

Animals
Biobehavioral Sciences
Early Diagnosis
Humans
Liver
Mitochondria, Liver
Oxidation-Reduction
Perfusion
Rats
Reperfusion Injury
Spectrum Analysis, Raman
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Article has an altmetric score of 2

Word Cloud

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