Storing donor lungs at a slightly warmer temperature – 10 degrees Celsius instead of 4 degrees – can make the organs viable for six times as long as traditional preservation methods for transplants, a new study found.
For decades, cold organ storage has relied on a simple ice cooler and a gold standard of 4 degrees. The new paper, published in Science Translational Medicine, may eventually change that practice and help erase some of the limitations that make it difficult for patients to receive successful and timely organ transplants, senior author Marcelo Cypel, surgical director of the transplant program at University Health Network in Toronto, told STAT.
The problem goes like this: Existing cooling protocols can keep a healthy lung in good condition for six to eight hours, which is not much time to find a transplant center with a suitable recipient and transport it there. By the time the organ arrives and is vetted, the patient is in the operating room, and a crew of clinicians is ready to go, there is little time left. Transplants often occur in the middle of the night because of this time crunch – a practice that other studies have shown results in worse outcomes for patients.
In the new study, researchers first tested the warmer storage temperature with pig lungs and then moved on to five human transplants, all of which were well-accepted by the patients, the authors said. The pig lungs could be kept viable for up to 36 hours, a big window that could transform the way transplants are done, Cypel said.
“You can really go anywhere to pick up an organ,” he said, “and that’s an advantage” because it opens the door to more patients and more of those organs in preciously short supply.
Despite a marked increase in organ donations over the last decade, the demand for lung transplants is often unmet, according to annual reports from the Organ Procurement and Transplantation Network. More than 20% of patients wait more than a year for a donor lung.
“We’re seeing the development of many types of technologies to keep organs viable longer. Some are even in clinical trials and the results are encouraging. The widespread implementation of any such technology may remove barriers to creating more equitable allocation policies and may lead to more lives saved,” said Ericka Lease, chair of the network’s Lung Transplantation Committee and medical director of the University of Washington lung transplant program.
The idea that storing lungs at a warmer temperature could open up access and keep the organs in better condition for longer isn’t new. As early as the 1980s, studies out of Japan and Toronto made similar arguments, to no avail.
“They were completely ignored,” Cypel said.
The difference now is how closely researchers can examine the organs. In previous studies, basic physiological assessments were used to determine how warmer storage worked; Cypel and his team, led by Aadil Ali, could study lung function at an intracellular level.
Toronto General Hospital, where Cypel works, has now performed 40 scheduled transplants “with really excellent results” as part of a clinical trial with lungs stored for up to 18 hours at 10 degrees Celsius, he said. A thoracic surgeon, he was one of the researchers who developed ex vivo lung perfusion, a method of preserving lungs at body temperature in an incubator that mimics the environment of the human body. While that’s an effective way of treating a less healthy lung and seeing how it might perform in the human body, these devices can tack $50,000 of technology costs onto each transplant case, said Cypel, a founder and shareholder of Traferox Technologies, which is developing alternative lung storage methods.
“It’s still worth it if you’re doing that for an organ you wouldn’t use otherwise,” he said, but storing lungs at 10 degrees could greatly minimize costs. All it would take to keep the organs at a warmer temperature is a cooler or refrigerator, which means “there is zero cost for maintenance, basically.”
If transplants could be scheduled during a 36-hour window, it would avoid having to perform middle-of-the-night procedures, and requiring patients to move near a hospital so they are ready when that call comes, he said. Without the geographic boundaries, patients could be matched with organs from almost anywhere in North America, reducing wait times.
The new study found that storing lungs at a 10 degrees could also make for smoother transplants. When a lung is kept at 4 degrees for longer than six hours, it starts to shut down, causing cells to become inflamed and die. At 10 degrees, lung cells are still performing some basic functions, like exchanging gases, and mitochondria — the cellular powerhouses — remain intact, possibly making it easier for a lung to transition into the new biological environment of the patient’s body, he said. That’s important because lung transplants have the lowest survival rate of any solid organ — 88.8% survive for one year, and that falls to 33.1% after 10 years.
The five patients included in the study all are alive and were doing well after a median of 330 days, the paper said.
Cypel said he plans to present findings from a larger, clinical trial to the American Society of Thoracic Surgery meeting in October. That work will compare five dozen transplants done with lungs kept at a 10 degrees to another five dozen transplants performed using regular storage during the same time period. A randomized trial might be next, Cypel said — and so might a broader question: Can this work for other organs, too?
Different organs are viable for transplantation for different lengths of time, and there are some physiological differences that could affect how well warmer storage works. Hearts cannot be kept on ice for more than four or five hours, a time limit that Cypel says is “a disaster.” For kidneys, it’s more like 12.
“To me, it makes a lot of sense that it would work better for other organs, too,” Cypel said. “So my colleagues for kidney and liver and heart, they looked at this data and they became very interested.”