Synthetic peptide may improve lung transplantation, according to a new research conducted by Medical College of Georgia scientists.
The study has appeared in the March issue of Critical Care Medicine.
Excess fluid and other problems that can occur within 72 hours of a transplant can significantly reduce short-term survival odds and long-term lung function. About 10 percent of patients experience an acute lung injury in the hours after their transplant, killing more than 40 percent of those patients within 30 days.
According to MCG researchers, putting the TIP peptide into the trachea of rat lungs about a half hour before transplantation can nullify the bad result, called ischemic reperfusion injury, and improve oxygenation.
Corresponding author Dr. Rudolf Lucas, vascular biologist in MCG's Vascular Biology Center, said: "We see the parameters of the transplanted lungs are nearly normal."
Reactive oxygen species are natural byproducts of oxygen use that can cause cell damage and death at high levels. Stress, such as putting dormant lungs back to work, can increase their levels.
Pointing out that donor lungs may be preserved in a cool, protective solution for several hours Dr. Lucas said: "Suddenly you put the lungs back in a body and you get an oxygen supply which by itself causes a lot of damage, mainly because of reactive oxygen species production."
A major potential problem immediately after lung transplantation is dysfunction of sodium channels in the alveoli, tiny air sacs where oxygen uptake occurs, impairing the sacs' ability to clear fluid into the lymphatic system. Moreover, researchers have documented an immediate invasion of white blood cells called neutrophils, which also produce reactive oxygen species.
Implicated in these early problems is tumor necrosis factor, or TNF, an inflammation-producing cytokine that helps the body fight infection, which can be deleterious, even deadly, at high levels, stated Dr. Lucas. The lung transplant activates TNF production, causing cells that line the organ's vasculature and air sacs to produce more reactive oxygen species and block sodium channels.
TNF can also have a polar opposite effect: blocking reactive oxygen species production and increasing sodium uptake. Dr. Lucas' team discovered this site, which binds to specific sugars, nearly a decade ago.
Unfortunately in the case of a lung transplant, the "bad" side is dominant; in fact, researchers from New Jersey Medical School refer to TNF's "Dr. Jekyll and Mr. Hyde saga" in an accompanying editorial in Critical Care Medicine.
That's where the synthetic TIP peptide comes in.
When scientists gave the synthetic peptide to rats undergoing lung transplants, the good side prevailed. Levels of reactive oxygen species and neutrophils dropped and sodium channels rebounded.
Soluble TNF receptors, which block TNF's "bad" action, already are being used to treat rheumatoid arthritis, in which the immune system attacks joints. MCG researchers have found that blocking this site does not block the positive-action, sugar-binding site.
Dr. Lucas said: "That means we have a physiologically relevant form of this peptide in our body, a cytokine that could help us avoid the problems that lead to ischemic reperfusion injury."