In experiments described as 'stunning' by experts, scientists were able to bring back to life vital organs of the pigs one hour after the animals died.
The research, according to the journal Nature, challenges the idea that cardiac death — which occurs when blood circulation and oxygenation stops — is irreversible, and raises ethical questions about the definition of death.
Nenad Sestan, a Yale neuroscientist and member of the team, quoted by the journal, predicted that these experiments might work in the light of the 2019 pig-brain study, because the brain is the organ most susceptible to oxygen deprivation. “If you can regain some function in a dead pig brain, you can do it in other organs, too,” he says.
According to the journal, Sestan’s team obtained pigs from a local farm breeder and monitored them for three days before sedating them, putting them on a ventilator and inducing cardiac arrest by delivering a shock to their hearts. After confirming a lack of pulse, they removed the animals from the ventilators. One hour after the pigs died, they restarted the ventilators and anaesthesia. Some of the pigs were then attached to the OrganEx system; others received no treatment or were hooked up to an extracorporeal membrane oxygenation (ECMO) machine, which some hospitals use in a last-ditch effort to supply oxygen to and remove carbon dioxide from the body.
After six hours, the researchers noticed that circulation had restarted much more effectively in pigs that received the OrganEx solution than in those that received ECMO or no treatment. Oxygen had begun flowing to tissues all over the bodies of the OrganEx animals, and a heart scan detected some electrical activity and contraction. But the heart had not fully restarted, and it’s unclear what exactly it was doing in those animals, says David Andrijevic, a neuroscientist at Yale University and research team member.
The researchers also noticed that the livers of the OrganEx pigs produced much more of a protein called albumin than did the livers of pigs in the other groups. And cells in each of the vital organs of the OrganEx pigs responded to glucose much more than did the animals in the other groups, suggesting that the treatment had kick-started metabolism.
The findings are striking given how quickly after death decomposition begins, says team member Zvonimir Vrselja, a neuroscientist at Yale University in New Haven, Connecticut. Within minutes of the heart stopping, the body becomes deprived of oxygen and enzymes begin digesting cell membranes, leading to organs rapidly losing their structural integrity.
The researchers also found that more genes responsible for cellular function and repair were active across all major organs in the OrganEx group compared with the ECMO or no-treatment groups.
ECMO is currently used in an attempt to preserve the organs of some dead people for donation, or to try to resuscitate people following a heart attack. For these purposes, doctors typically need to start ECMO soon after the heart attack or death — and success rates can be low, depending on injury severity, says Sam Shemie, an critical-care physician at the McGill University Health Centre in Montreal, Canada.
Given the difference in how the pigs’ organs fared with OrganEx compared with ECMO, this is potentially a “landmark” study that could “significantly increase the number of organs that could be recovered for transplantation”, says Gabriel Oniscu, a transplant surgeon at the Royal Infirmary of Edinburgh, UK.
Before that can happen, further research to assess the viability of the recovered organs will be crucial, says Shemie.
With these potential implications come ethical challenges, says Farahany, especially if the technique could one day restore brain activity after death.
The researchers note that electrical activity in the pigs’ brains might have been absent because the solution they pumped through was colder (28 ºC) than normal body temperature, or because it included anaesthetic compounds and neuronal blockers that could have suppressed such signals. Farahany says it will be important for future researchers to test for any restoration of brain activity, particularly in light of the neck-jerking the researchers observed during the experiment.
The journal added that the study also further emphasizes that death is not a moment but a process, making it challenging to come up with a uniform way to declare a person dead, says Arthur Caplan, a bioethicist at New York University. That means that the legal definition of death will continue to adapt as medicine continues to advance, he adds. “People tend to focus on brain death, but there’s not much consensus on when cardiac death occurs,” he says. “This paper brings that home in an important way.”