Repairing injured lungs for transplantation

14 May 2019

Interview with 

Matthew Bacchetta, Vanderbilt University

LUNGS-ANATOMICAL

The image shows a pair of lungs.

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Thousands of people die every year waiting on transplant lists. And lungs are in particularly short supply. Now scientists might have found a way to increase the numbers of donor organs that are suitable for transplantation. In experiments using pigs, which have lungs very similar to ours, Matthew Bacchetta from Vanderbuilt University has found that if he takes injured lungs that would normally be unsuitable for transplant, and plumbs them in to a potential recipient’s circulatory system for a day or so - but keeps the lungs outside the body in a special organ chamber - nourished by the healing effects of the blood supply, they recover very rapidly to a state that means they can then be moved inside the recipient. Matthew spoke to Chris Smith...

Matthew - Lungs are extremely sensitive to injury from gastric aspiration, pulmonary contusion, meaning that the lung gets bruised, getting infected while the patient is on a ventilator so they could develop a bacterial infection like pneumonia, and those are the primary reasons that organs are deemed unacceptable for transplantation. The major thrust of what we've done here is replicate the injury that we see in humans. We used what we call a gastric aspiration; what that basically means is that the patient has taken gastric contents, which are very acidic and caustic, into their lungs and it causes inflammation like a severe pneumonia so that the organ cannot be used. And what our system has enabled is the organ to regenerate or repair itself over time.

Chris - How have you done it?

Matthew - We first failed a lot trying different types of ex vivo systems, meaning the organ was placed outside the body separated into a sort of machine perfusion system. And after being very frustrated and failing repeatedly, we eventually sort of had the 'eureka' moment where we said we can't replicate a whole system but what we can do is attach the organ to a natural host or recipient. In other words, the organ could be attached to somebody who needs potentially a lung transplant and that body provides the whole natural system required for wound healing. What we have essentially done is plumbed this organ into the potential recipient who provides all of the critical factors in their blood that enable the organ to heal.

Chris - So where did the lungs sit then, are they in the bath next to what will be the patient? When you actually come do this you’re gonna end up with some tubes coming out of the individual bringing the blood to and from these lungs which are going to be outside their body next to them?

Matthew - That's correct. That's exactly what we do. They are in a specialised container - it actually looks very similar to what we would do for a patient that was on dialysis, they would have blood coming out, it would go into the dialysis machine and then that blood is returned to the patient.

Chris - Does the lung breathe as well as? Are you pushing air in and out of the lungs you do this to keep it natural and what it would be expecting were it inside the body, to create as much a mimic for what the real body environment would be like?

Matthew - It does. We connect it to a mechanical ventilator and we can actually measure the performance of the organ in real time.

Chris - So you're looking at how much oxygen is getting pushed into the blood that your pushing through it by that set of lungs, so that gives you a marker for how well they're behaving and what the improvement is?

Matthew - That's correct, exactly. So we can monitor that over time and that gives us a benchmark to monitor the improvement process and to also let us know when we've reached a level that's normal.

Chris - Why is this better than just putting the lungs into the individual full stop? Because you're basically doing the same thing, you're sending them a blood supply, you're sending them an air supply, why is that better doing it outside body than just putting them in?

Matthew - Yeah, that's a great question. The major difference is that you have to subject the patient to a very invasive procedure. I have to remove their lungs, I have to put in new lungs, and we know that the lungs are damaged, that they're not really acceptable for a transplant. And then I have to support that patient with damaged lungs which causes a profound inflammatory process and so the body actually does not actually work as effectively in healing those lungs and the patient becomes unstable because they're now relying upon an injured organ to keep them alive.

Chris - And how did the recipient fare while they've got this extra set of lungs hitched up to them, and not just any old lungs, someone else's lungs, some other animal's lungs, and diseased lungs at that? Was there an obvious burden on the individual or did they cope well?

Matthew - They actually coped remarkably well. They were hemodynamically stable, meaning that their blood pressure, their heart rate, and all of the other physiologic measures that we use were normal and stable.

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