For patients awaiting a new heart or new lung, time is of the essence.
Along with the complexity of a lifesaving transplant – including potential rejection – there simply aren’t enough available organs for those who need them. Even after a match is found, the clock is still ticking: The organ can only survive outside the human body for a limited timeframe.
However, new techniques pioneered at UCLA Health for preserving donated organs prior to transplantation are continuing to broaden this window.
A leading center for transplants and research
UCLA Health has long been a leader in cardiothoracic transplants: It performed its first heart transplant in 1984 and its first lung transplant in 1990. In 2024, it performed 88 heart transplants and 92 lung transplants.
Of the various organs that can be transplanted, the heart is the most “metabolically complex,” said , director of the UCLA Heart, Lung, and Heart-Lung Transplant Programs, and professor of surgery and medicine at the David Geffen School of Medicine at UCLA.
As a result, the maximum time a donated heart can be placed in a state of cold storage – the dominant method for transporting organs – is just six to eight hours. After that, the heart starts to show damage and is no longer suitable for transplant.
“Human organs were never meant to be kept ice cold,” Dr. Ardehali pointed out.
Until about 15 years ago, however, transporting hearts and other organs always entailed just that: After being removed from the donor’s body, the organ would be placed in a large cooler and transported in a near-freezing state, a process known as static cold storage.
Under Dr. Ardehali’s tenure, UCLA Health has played a leading role in using new methods for preserving donated hearts and lungs prior to transplant. While the specifics vary, the new methods dial up the temperature and keep the organs functioning during transit.
Transporting hearts in a beating state
The first nationwide study to test a new method for transporting donated hearts ran from 2010 to 2013. UCLA was the largest enrolling participant, and Dr. Ardehali was the principal investigator.
During these pioneering trials, 130 patients received donated hearts that had been transported in a warm, beating state inside a specialized box developed by an outside medical device company. The process is known as ex vivo (“outside the body”) perfusion. In this case, the blood circulating through the donated hearts was kept at the temperature of the human body: 37 degrees Celsius (98.6 degrees Fahrenheit), or what’s called “normothermic” temperature.
“The benefit of ex vivo organ perfusion is to continually provide nutrients to the human organ, and also remove the toxic products,” Dr. Ardehali said, “maintaining the organ in better condition and making it a better organ for transplantation.”
The technology for normothermic ex-vivo perfusion, which allows the heart to be in a near-physiologic state during transport, received approval by the Food and Drug Administration in 2021.
Since then, this method of perfusion has broadened the pool of available organs by allowing hearts donated after circulatory death to be used for transplant. Previously, Dr. Ardehali explained, all hearts used for transplant came from donors who had been declared brain-dead. After brain death, the heart is still functioning and blood is still circulating through the organs. While organ donation from brain dead donors remains the major source of donor organs, donation after circulatory death is being increasing seen.
That’s where warm perfusion comes in: By artificially maintaining hearts in a beating state, it enables hearts from circulatory death donors to be resuscitated and used for transplant. It used to be that 100% of donated hearts came from brain-dead donors; now, about 10% come from donors following circulatory death, Dr. Ardehali said.
“Machine perfusion along with other techniques have made heart donation after circulatory death possible,” he explained.
Expanding perfusion for use with lungs
The next organs to be tested with warm perfusion were lungs, which can last a bit longer than hearts in cold storage but still had a maximum viability window of 12 hours with this method. Again, Dr. Ardehali served as the principal investigator for the FDA-approved trial.
“For human lungs, we were the first center in the country that actually used ex vivo organ perfusion and proved that it worked in an experimental setting,” he said.
In this case, the lungs were perfused with a partial plasma solution, creating a “breathing lung” system for transporting them in a functional state and extending the timeframe for them to remain viable.
UCLA was the first medical center in the country to perform a “breathing lung” transplant in 2012; the technology used during the trial was subsequently approved by the FDA in 2019, and there are now two different FDA-approved devices for perfusing lungs, Dr. Ardehali said.
Lung perfusion is currently used (rather than cold storage) in transplant situations where it offers a clear benefit, Dr. Ardehali said, such as transporting lungs longer distances.
However, he noted that “the jury was still out” on whether perfusion was a better method of preserving lungs than cold storage. This may be because of differences in cold storage transport for lungs compared to hearts: Unlike with hearts, Dr. Ardehali explained, lungs transported via cold storage still have access to oxygen.
“We inflate the lungs with oxygen, and it stays there during transport,” he said. “It’s on ice, but its cells still have access to oxygen in the airways in the lung.” This makes the potential for metabolic damage less than it is for hearts being transplanted via cold storage and may be why perfusion is used less often for lungs, he noted.
Testing a colder form of heart perfusion
The most recent FDA-approved trial, for which UCLA was one of the largest enrolling centers, focused on a new heart-perfusion method in which the blood circulating through the heart was 8 degrees Celsius (46.4 degrees Fahrenheit) – still cold, but not at the near-freezing 4 degrees Celsius (39.2 degrees Fahrenheit) used during cold-storage transport.
The study concluded in late 2024 and included about 130 patients total, Dr. Ardehali said, with about 20 of those transplants taking place at the Ronald Reagan UCLA Medical Center.
“What I can say, based on our local experience, is that we were impressed with the preservation platform,” he said. “Being able to perfuse the donor heart at 8 degrees appears to preserve the heart better, in our limited experience, and we anxiously await the review by the FDA and final approval.”
In his preliminary assessment, it may be that the 8-degree model is more effective than either normothermic perfusion or cold storage.
“Warmer hearts have a higher metabolic requirement: They need more blood and more oxygen, because they’re a normal thermia,” Dr. Ardehali said. “On the other end of the spectrum, when the heart is on ice, there is an element of injury to the heart because of the contact with the ice. This fine line of maintaining the donor heart at 8 degrees and continuously perfusing it appears to be uniquely capable of preserving the heart in good condition for transplantation.”
Continuing to innovate
There are “thousands of permutations” that can be evaluated – and potentially can be modified – as perfusion technology evolves, Dr. Ardehali noted. These variables include the temperature, blood pressure, and fluid content (partial plasma or blood), as well as the entry point for perfusion, he explained. “For example, with the liver, you can (initiate perfusion) through the portal vein or the hepatic arteries,” he said.
“The challenge,” he noted, is to identify the best condition and content for perfusion to ensure that the organ is preserved to its fullest potential. We’re not there yet, but we’re making progress.
“There will be a day when we’ll have this fine-tuned so we know exactly how much blood we should put in there, at what pressure, and under what circumstances, and at what temperature we should perfuse the donated organ, so that we’ll have the best chance of that organ working,” he said.
As new perfusion methods emerge, Dr. Ardehali expects UCLA Health will continue to play a leading role.
“We were the largest center in the first trial that used organ perfusion for human hearts, we did the first breathing lung transplant in the United States, and now we are using this commonly in the liver program,” he said. “We have been very engaged in all aspects of organ transplantation, and virtually every trial that involves ex-vivo organ perfusion, they always reach out to UCLA because of our expertise. UCLA has been, and continues to be, the leading center in this area, and that is what sets us apart.”
