Ex-VivoLungs are the most vulnerable of all organs.  Indeed,  when it comes to viable transplants, the lungs fall far behind other solid organs.  This country transplants 10 times more kidneys than lungs, four times as many livers, and 40 to 50 percent more hearts.  “Lungs are incredibly delicate. They are the least recoverable and the first organ to go bad,” said Edward Cantu, MD, of Cardiovascular Surgery.  “In the U.S., only 15-20 percent of potential donors have viable lungs for transplantation.”

Now, a new technique at Penn repairs damaged donated lungs that would have otherwise been unusable, allowing for the successful transplantation of the reconditioned lung.   Called ex vivo lung perfusion (EVLP), the process could potentially double the number of usable lungs for patients awaiting transplantation.

How Does EVLP Work?

As a person breathes, air travels down into the lungs, passing through the bronchial tubes and into the alveoli (air sacs).  Oxygen goes through a thin membrane into blood vessels as carbon dioxide is removed from the bloodstream.  When death occurs,  tiny holes develop between the lung and the membrane;  water seeps into the lungs from the blood vessels.  “All the alveoli that contribute to the breathing process fill with water,” Cantu explained.  “The lungs are basically drowning.”  

As a result of this post-death occurrence,  the faster the lungs can be removed from the donor, the less damage they will suffer.  Unfortunately, the procurement process – when transplant teams remove organs from a donor  -– can also adversely affect donor lungs. “My team wants the lungs as dry as possible, to protect them,” he said. “But the other procurement teams want more fluids given to keep their respective organs working well.  We have competing interests.”

EVLP removes this extra fluid from the lungs, helping to reverse lung injury.  During the three- to four-hour process,  donor lungs are placed inside a sterile plastic dome attached to a ventilator, pump, and filters.  The lungs are maintained at normal body temperature and perfused with a bloodless solution that contains nutrients, proteins, and oxygen.  “The solution was developed specifically to protect the lung.  It contains recombinant albumin, which acts like a sponge, pulling water out of the organ.”

EVLP not only potentially repairs the lung, but also provides an extended period of evaluation to measure the quality of the donor lung.  “Getting the lung into this controlled environment allows us to monitor specific parameters,” he said, including how well the lung oxygenates, the peak airway pressure (ie, how much pressure is needed to inflate and ventilate the lung), and lung compliance, which is a measure of how stiff the lung is. 

“Lungs are like two big balloons.  The more elastic they are, the more capable of doing their job,” said Jaya Tiwari, CCRP, who works with Cantu as project manger for the Novel Lung Trial. This multicenter clinical research trial is designed to compare outcomes from lung transplants using the ex vivo technique with those using the traditional method. 

“If the lung stays stable during EVLP and oxygenates well, we’ll use it,” he said “But if the lung starts to deteriorate during perfusion, we can tell it’s not good for transplant.”


Same –- or Better -- Results

As part of the Novel trial, Cantu performed the EVLP procedure on the first patient in the region last month, using lungs that had been turned down by another transplant center outside of the area.  “The lungs were procured by another team and brought to us by courier,” he said.  “We were able to put them on the perfusion machine and evaluate them. The patient had fantastic results. Ordinarily we’d never have had that opportunity.  This is good for both the donor and recipient families.”

EVLP  has been used in Europe and Canada for many years. Cantu said that results from a 2010 clinical study in Toronto -– the largest so far in the world –- showed that patients who received perfused lungs had the same survival rate and length of time on a ventilator, in the ICU and in the hospital as those with organs that were transplanted normally. In fact, “the numbers in the perfused organs are trending to shorter times and less injury, so this process may potentially be better,” he said. “This raises the question: should we do all donor lungs? Would this decrease the length of recovery time in all lung transplant patients?”

Not every lung reconditioned through EVLP will meet the transplant criteria, Cantu noted, but even if not suitable for transplant, “we can use them for study, for example, to better define pneumonia or better understand ventilator injury.  All these things we can do because we can keep the lung alive for an extended period.

“This is truly the beginning of a new tomorrow, opening a door to many, many possibilities,” Cantu said. “If we can make more organs available, fewer transplant patients will die waiting.

Photo caption: Edward Cantu, MD (r.) works with procurement surgeon Yoshikazu Suzuki on a donor lung undergoing ex vivo lung perfusion.

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