Health

Researchers ‘revive’ organs in dead pigs, raising questions about life and death


‘If you can restore a lot of these organs, how dead is the person?’

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Scientists have rebooted vital organs of dead pigs in an experiment bioethicists say may force a rethink of how the body dies and that further blurs the boundaries between life and death.

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Using a system dubbed “OrganEx” that uses special pumps and solutions to restore oxygen and prevent cell death throughout the body, the Yale University team restored blood circulation and other cellular functions in multiple porcine organs an hour after the pigs’ deaths from cardiac arrest.

They saw electrical activity in the heart, for instance. It started pumping again.

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The study “reveals the underappreciated capacity for cellular recovery after prolonged whole-body warm ischemia (loss of blood circulation, and thus oxygen) in a large mammal,” the team reports in the journal Nature.

The experiments also bolster findings from another Yale-led project three years ago that involved disembodied pigs’ brains. Using a similar perfusion system called BrainEX, researchers restored circulation and cellular activity in brains taken from pigs four hours after they were killed in a meatpacking plant.

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That was an isolated organ. The team wondered, could they apply a similar approach on a whole-body scale?

Together, the research challenges old thinking that the body’s cells and organs begin to be irreversibly destroyed within minutes of the heart stopping. Instead, “cellular demise can be halted, and their state (can) be shifted towards recovery at molecular and cellular levels,” the Yale team writes in Nature.

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The work has the potential to help reduce the amount of damage that is done to people’s brains after a stroke, and maybe hearts after a heart attack.

drawing showing the difference between pigs put on the OrganEx system versus those put on BrainEx.
drawing showing the difference between pigs put on the OrganEx system versus those put on BrainEx. Photo by David Andrijevic, Zvonimir Vrselja, Taras Lysyy, Shupei Zhang; Sestan Laboratory /Yale School of Medicine

But the greatest benefit might come in expanding the supply of donor organs for transplant. And there’s where things get ethically complicated.

Donor organs can be retrieved from people who are declared brain-stem dead. They’re medically and legally dead, but their hearts are still beating. But seat belt and helmet laws and advances in treating brain injuries means fewer people are dying from brain death.

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A trend now is to harvest organs from “donation after circulatory death” donors, typically people on life support with such a bleak prognosis the decision to remove life support is made. Once the heart stops beating and doctors wait the obligatory five minutes before declaring death, the donor organs are retrieved. But surgeons must move quickly. The organs deteriorate once starved of a blood supply and oxygen.

OrganEx has the potential to give doctors more time to retrieve the organs after life support has been switched off.

But that approach would also require the “obligatory” clamping of the main arteries supplying blood to the brain to prevent any blood reaching the brain of the deceased organ donor, the Yale team notes.

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In both the BrainEX and OrganEx experiments, the researchers, who did continuous EEG (electroencephalography) monitoring of the animals’ brains, found cellular activity in some areas of the brain had been restored. At no point did they see the kind of electrical activity that would indicate consciousness or awareness, they said.

However, they did see spontaneous movements of muscles in the head, neck and torso in the anesthetized pigs treated with OrganEx. The EEG patterns were flat immediately before and after the movements. But the movements indicate some “preservation” of motor functions, the researchers said.

The implications are just so phenomenal

The OrganEx system works much like a heart-lung bypass machine. The perfusion device is connected to the pig’s circulatory system. A synthetic fluid that contains Hemopure, a blood-like product and other chemicals that promote cellular health, decrease cell death and suppress inflammation is pumped throughout the animal’s body.

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The researchers induced cardiac arrest and then treated pigs with the OrganEx system an hour after death. They animals were compared to a group of pigs put on ECMO, or extracorporeal membrane oxygenation, a machine that pumps the pig’s own oxygenated blood throughout the body.

After six hours of treatment, the scientists saw decreased cell death, and restored activity in the heart, liver, kidneys and pancreas in the OrganEx group. Unlike the ECMO pigs, the hearts could still contract.

It doesn’t mean the organs were functionally normally, said first author David Andrijevic, an associate research scientist in neuroscience at Yale School of Medicine. “The next step is that we’re hoping to see complete tissue and organ recovery and, of course, eventually, to transplant these organs.”

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But the team was surprised by how much they were able to restore circulation throughout the body. This wasn’t a 200-gram pig brain but 30-35-kg swine, Andrejivic said.

“The implications are just so phenomenal as I see it,” said University of Toronto bioethicist Kerry Bowman.

“With heart attack and stroke, I say, hallelujah, because so much harm is done so quickly and if something like that is going to help, that would be wonderful.”

He’s also pro-transplant — “I’m not anti-transplant in any way, shape or form.” However, “what hits me like a tonne of bricks is that you are really manipulating the boundary between life and death.”

It’s like throwing a switch, he said. Living, dead, living, dead. “If you can restore a lot of these organs, how dead is the person?”

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“What they are proposing here is that a person would be taken off life support, declared dead, perfuse them with Hemopure and then insert a balloon to block access to the brain,” Bowman said. “And the reason for that is you would not want any brain activity, because that would raise questions as to whether this person was truly dead or not.”

I think we need a lot more clarity as to where this is going

“Once you’ve been declared dead you would kind of reanimate aspects of this person to use their organs, while blocking their brain,” Bowman said.

“There is no indication that if you didn’t do that, that this person would recover or have any level of consciousness. (But) we simply don’t know those things…. I think we need a lot more clarity as to where this is going.”

“Cellular activity” isn’t the same as coming back into human existence, said Arthur Caplan, a medical ethics expert at NYU. The experiment is important for “trying to figure out what can be restored, what can be resuscitated, what can be partially restored after death.”

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However, “if you can get biological activity in cells, in muscles, and they’re moving and you seem to see signs of what I’ll call ‘life’ in a body, in an animal that’s been dead for an hour, do we need to rethink how we understand cardiac death, not brain death.”

“If you could get some function back by putting in this OrganEx solution, would that mean that should be tried on people whose hearts have stopped before we pronounce them dead?”

The experiment is a reminder that death is a process, rather than an abrupt event, Caplan said. “Yes, your brain my stop, your heat may stop but other parts of the body may peter out as opposed to all shutting down” within seconds.

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“I think a lot of people are likely to assume that when you’re dead, everything is dead all at once. This experiment suggests me that isn’t true.”

A lot more animal work would be needed to be 100 per cent certain “that you couldn’t get meaningful brain activity back,” Caplan said. “What I personally believe to be true, watching a lot of organ procurement over the years, and a lot of dying, is that the brain is much more vulnerable.”

“When we see someone whose heart hasn’t worked for five minutes, we know their brain is gone,” even if it means getting something in their liver to work, Caplan said. “Tying off flow to the brain would not be trying to fudge the definition of death.”

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