New research at the
University of North Carolina at
Chapel Hill School of Medicine shows that treatment with nitric oxide after storage may dramatically improve the viability of transplanted livers.
About 5,000 liver transplants are performed annually in the United States, and a key factor ensuring success is maintaining a healthy donor organ that can function effectively in the recipient. However, transplanted livers typically incur substantial damage when blood flow is restored to the organ after the transplant.
This damage occurs when ischemic, or oxygen-deprived, tissue is re-introduced, or reperfused, to adequate blood flow.
The study, to be published in the June issue of the journal Hepatology, showed that use of nitric oxide during reperfusion protected cultured rat liver cells, or hepatocytes, from cell death typically occurring as a result of reperfusion stress.
"Reperfusion stress precipitates the death of the tissue, but our results suggest that the way we reperfuse the liver can reduce injury to it," said Dr. John Lemasters, professor of cell and developmental biology at UNC and senior investigator for the study.
Preventing such damage is relevant in liver transplants and essential to the success of organ transplantation in general, UNC researchers said.
This injury also is central to the nature and development of shock, stroke and heart attacks, Lemasters added.
Cell death due to reperfusion stress results from damage to the hepatocyte's mitochondria, the cellular site of generation for the primary energy molecule in a cell, called adenosine triphosphate (ATP). This damage, known as mitochondrial permeability transition (MPT), opens up the mitochondria to small molecules entering the organelle and interrupting generation of ATP. Then, cell death occurs.
Nitric oxide exerted its protective effects in the study's model by blocking the MPT-based injury to the hepatocyte, the study showed.
"Our cell culture model mimics severe ischemia, and nitric oxide was still effective in blocking cell death," said Dr. Jae-Sung Kim, the primary study author and assistant professor of cell and developmental biology.
Use of nitric oxide after cold storage of the donated organ may help maintain normal liver function after the transplant, the study indicated.