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

机器灌注过程中肝脏线粒体氧化还原状态的无创量化

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作者: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

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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