The Ex-Vivo Organ Support System, currently being tested at the University of Alberta Hospital.
COOPER & O’HARA
We’ve all suffered more travel-related headaches than we can remember. We know what it’s like to get stuck in rush-hour traffic on Whitemud Drive or have an unexpected snowstorm reduce visibility to zero, leaving us inching down the highway.
We’ve shown up at the airport on a snowy day to see the departures board covered in “delayed” and “cancelled” notifications.
At worst, delays like these mean we end up late for work or miss a flight connection. But for Dr. Jayan Nagendran and the rest of the lung transplant team at the University of Alberta Hospital’s Mazankowski Alberta Heart Institute, delays can mean the difference between life and death.
The catchment area for the University of Alberta Hospital’s lung-transplant program is huge, covering the better part of four provinces and three territories — a total of approximately six million square kilometres. That’s one-third the size of Russia. Patients from as far away as Winnipeg, Regina, Yellowknife and Prince George are all eligible to be treated at the hospital. And organ donors can come from anywhere in the area as well.
“The geographic isolation we face is unlike anyone else in the world,” says Nagendran.
Despite the unique challenges posed by these vast distances, Edmonton is one of the busiest transplant hubs on the planet. In 2018-19, the University of Alberta Hospital performed 60 lung and two heart and lung transplants, which puts it in the top 10 per cent globally.
It’s what Nagendran calls a “dramatic” operation. When the team gets word that a donor has been identified, members fly to that city, where they will operate to remove the organs. This is an incredible gift — in death, the organ donor potentially passes on the gift of life. Meanwhile, back in Edmonton, other team members begin preparing the recipient for the lungs that are scheduled to arrive in a few hours. It’s a ballet performed on two stages. The problem is, the doctors can only control so much.
Not even taking into account travel-related setbacks, with the current system, only about one in four donated sets of lungs are healthy enough to be transplanted. Many are too damaged, meaning that one in three people on the waitlist die before they can get their life-saving procedures.
Even if the removal goes smoothly, the lungs have to get to the airport as quickly as possible. Of course, the ambulance rushes the team there with the lungs on ice, but, even with sirens on, ambulances can be slowed by heavy traffic, bad weather or an accident that blocks the road.
Meanwhile, while sitting on ice, lungs deteriorate. After six hours on ice, damage starts to show. After eight hours, irreparable damage overtakes the lungs.
Once on the plane, the team can fall victim to flight-crew changes or weather delays. Nagendran recalls a time when headwinds forced a plane to make an unscheduled fuel stop, which cost hours.
Once in Edmonton, it’s back to the ambulance where, once again, traffic can be a factor.
There can also be unforeseen problems with the recipient. “All the imaging in the world can only tell me so much,” says Nagendran. He can only really know what he is dealing with after he’s begun surgery, made the incisions and seen what needs to be done. Sometimes, at that stage, the doctor will discover hours of surgery are needed before the transplant can actually be performed. And that means the lungs sit on ice that much longer.
Thanks to the innovative work of Nagendran and Dr. Darren Freed — a cardiac surgeon and associate professor with expertise in keeping organs alive outside of the body — putting lungs on ice and all the problems that come with that may become things of the past.
Together, the two doctors have created a system they call EVOSS (Ex-Vivo Organ Support System). This machine, which looks a bit like a mini refrigerator with valves and tubes mounted to its shell, has the potential to change the way organ transplants are performed. Instead of being stored on ice, lungs are put in the new machine, which supplies blood and oxygen. Because EVOSS uses a vacuum chamber, which mimics how humans breathe, the lungs actually stay alive in the machine.
The University Hospital Foundation has granted $450,000 to set up the lab at the University of Alberta.
The University Hospital Foundation has granted more than $520,000 to support multiple research projects.
This second grant generated the results to initiate a first-in-patient clinical trial another $100,000 came from the Alberta Transplant Innovation Fund, specifically to support the trial. The two doctors have formed a company, Tevosol, to help advance the technology.
Nagendran and Freed’s work is in the clinical trial stage, with 12 patients scheduled to receive transplants with lungs preserved by EVOSS. Eight of them have already received their transplants, and so far none have shown signs of severe lung dysfunction, the usual sign of rejection. “It’s beyond what we expected,” says Nagendran.
Because EVOSS keeps lungs alive, transplants will no longer be races against the clock. If a plane is delayed, EVOSS keeps the lungs warm and breathing. This innovation could allow surgeons to schedule transplant surgeries.
“We want to take time right out of the equation,” says Nagendran.
But there’s more. EVOSS could also increase the number of organs that could be used in transplants. As mentioned, only about 25 per cent of donors’ lungs are healthy enough to be used in transplants. In the EVOSS clinical trials, doctors have used lungs that would have failed the viability tests. That’s because living lungs can be treated and repaired in the chamber, something that can’t be done with lungs on ice.
Examples? Nagendran was able to clear a blood clot from a pair of donor lungs by administering anti-clotting agents while they were in the EVOSS chamber. In another case, lungs from a donor who suffered from pneumonia were given massive doses of antibiotics and cleared out before transplant.
While on the machine, these lungs aren’t connected to a human body, so doctors can use extraordinary measures to treat them. Doctors don’t have to worry about massive antibiotic dosages that would cripple livers or damage kidneys. They don’t have to worry about the collateral damage that extreme lung treatments could inflict on other organs. Extreme measures to make the lungs viable can be taken.
The possible applications are incredible. What if a patient suffering from lung cancer could have a lung removed and put on EVOSS? The lung could be subjected to heavy chemo-therapy, then returned to the patient. This innovation opens up the possibility of treating sick organs outside of the body, the stuff of what was once science fiction.
“We want to make sure that no one dies on waiting lists,” says Nagendran. “And it would make transplants global. If we found a perfect match in Germany, we’d be able to do the transplant. This also opens us to medical collaborations we can only dream of. We want everyone to know that we’re going to do everything possible to honour the organ donor’s precious gift of life to others in dire need.”
How we Breathe
EVOSS mimics human breathing by using negative pressure. What does that mean? As Nagendran explains, we breathe by expanding our chest cavity and creating a vacuum in our lungs, which sucks in the air.
Currently, in any form of medical procedure, assisted breathing uses a ventilator that pushes air into the lungs. That’s called positive pressure. Since positive pressure is not how we breathe, it causes damage to the lungs over time. Doctors Freed and Nagendran have created a way to preserve lungs by avoiding harmful positive-pressure ventilation and doing it the way we all breathe right now, by negative-pressure ventilation.
The sealed chamber in EVOSS creates a vacuum and the lungs inflate naturally, just like we breathe. So the lungs are functioning normally; they’re actually “breathing” inside the chamber. They are, essentially, alive.