David Hall, M.D., a fifth-year general surgery resident in the University of Florida College of Medicine, has received a grant through the American Lung Association for research that could significantly increase number of donor lungs available for transplant.
His project seeks to determine whether a medication that blocks an inflammatory pathway — known as Endothelin-1, or ET-1 — can improve the health of lungs on ex-vivo lung perfusion, or EVLP.
ET-1 blockers are currently used to treat pulmonary hypertension. The drugs work by preventing blood vessels from constricting, which can cause pulmonary artery pressure to escalate. Hall believes the medication might work in a similar way on lungs on EVLP.
“EVLP, a novel organ preservation technique, has been repeatedly shown to enhance the safety of marginal donor lungs, with similar short and long outcomes as those obtained with standard criteria lungs,” Hall said.
EVLP allows surgeons additional time to evaluate a set of donor lungs and — in some cases — organs otherwise not viable for transplant can be rehabilitated. During the process, a machine pumps a special preservation solution and oxygen into the lungs over a course of four to six hours.
Traditionally, the lungs remain inside the donor while a surgeon evaluates the organs considered for transplant. Such assessments may not provide all the information the transplanting surgeon desires, and it can be difficult to reach conclusions about the organs’ viability at that point in the process.
Some lung damage, like pulmonary edema or impaired gas exchange is reversible, noted Hall’s mentor, Tiago N. Machuca, M.D., Ph.D., an assistant professor in the division of thoracic and cardiovascular surgery.
“If those conditions are addressed, the lungs might be excellent candidates for a successful transplant,” he said.
Approximately two out of every 10 sets of donor lungs now are accepted for transplant. Machuca estimates that 50 to 60 percent of donor lungs placed on EVLP could become suitable for transplant.
If successful, Hall hopes his preclinical research will spur a clinical trial of the effects of ET-1 blockers on lungs placed on EVLP.
“Dr. Hall’s work is part of a very exciting body of research on EVLP,” Machuca said. “We are hopeful that his work can lead to an increase in the available pool of donor lungs.”
The $32,500 Senior Research Training Fellowship grant runs from July 2017-June 2018. The funding supports first-time scientific investigators who have recently graduated with a medical degree or doctoral degree. Under the fellowship, the research projects must focus on the mechanisms of lung disease and general lung biology.