Discovery of lung transplantation could improve survival rates

University of Virginia School of Medicine researchers have identified a potential way to improve the survival rate of lung transplant patients.

For many patients with advanced or terminal respiratory diseases, lung transplants are the only treatment option. Survival rates for patients after lung transplants have improved in recent years, but remain far behind those of other organ transplant patients.

This prompts doctors and researchers to look for ways to improve the process and prevent or reduce post-transplant problems.

A team, led by Swapnil K. Sonkusare of UVA’s Department of Molecular Physiology and Biological Physics, has identified cellular changes in the lung following transplantation that contribute to “ischemia-reperfusion injury,” a cause major rate of organ rejection and death after transplantation. . Injury occurs when blood supply returns to the tissues after a period without oxygen.

Sonkusare and his team found that by targeting underlying biological processes, doctors could prevent ischemia-reperfusion injury.

The results are published in the journal Scientific signage.

“Our collaborative studies with Dr. Victor Laubach of (UVA’s) Department of Surgery show a new mechanism of pulmonary ischemia-reperfusion injury,” said Sonkusare, of UVA’s Robert M. Berne Cardiovascular Research Center. . “This mechanism could be targeted to improve the clinical success of lung transplantation.”

Better lung transplants

Ischemia-reperfusion injury is a major cause of so-called “primary graft dysfunction,” the leading cause of death within 30 days of lung transplantation. It can also lead to chronic allograft dysfunction, the leading cause of death a year or more after transplantation. Half of lung transplant recipients develop chronic allograft dysfunction within five years after transplantation, according to the National Institutes of Health.

At least some degree of ischemia-reperfusion injury is inevitable for patients who undergo organ transplantation. Tissues are traumatized when they are disconnected from their original blood supply and reconnected to a new one. For lung transplants, this trauma can lead to harmful inflammation, leaking blood vessels, damage to the tiny sacs responsible for oxygen exchange, and other problems.

Although the phenomenon of ischemia-reperfusion is well known, researchers have struggled to understand its underlying causes. Sonkusare’s new work provides answers, identifying a particular pathway of biological processes triggered by ischemia-reperfusion. These processes occurred in the endothelial cells that line the blood vessels of the lungs and resulted in activation of immune cells leading to lung damage, according to the UVA researchers.

Scientists found that blocking key steps in this pathway prevented lung inflammation and damage in laboratory mice, suggesting a promising approach to preventing the same problems in human transplant recipients, although much research more in-depth will be necessary.

“Our collaborative research with Dr. Laubach revealed the cellular mechanisms responsible for pulmonary ischemia-reperfusion injury,” Sonkusare said. “We are currently testing the effectiveness of drug molecules that block these mechanisms in various models of lung injury after transplantation, with the ultimate goal of improving the success rate of lung transplantation.”

The research team consisted of Maniselvan Kuppusamy, Huy Q. Ta, Hannah N. Davenport, Abhishek Bazaz, Astha Kulshrestha, Zdravka Daneva, Yen-Lin Chen, Philip W. Carrott, Laubach, and Sonkusare.