In 2019, neuroscientists and doctors from Yale University (USA) managed to restore part of the brain function of a pig that had been slaughtered in a slaughterhouse four hours earlier. Now the same group has repeated the feat, but in all the vital organs of several pigs that had been dead for an hour. The study recently published in Naturerelied on a kind of complex injection system great blood Synthetic that reversed cell death. This breakthrough opens a new avenue for organ transplantation but raises new questions about the time of death.
After the last heartbeat, a chain of events begins: lack of blood supply (ischemia) implies the lack of oxygen and other essential elements, which leads to the death of cells, tissues, organs and the entire organism. In this study, scientists induced cardiac arrest in dozens of pigs (they had previously been anesthetized). After an hour without a blood supply, meaning dead, they were divided into several study groups: Some were hooked up to a life support system used in severe cases where the heart and lungs stop working (ECMO, for its English acronym for extracorporeal membrane oxygenation). Others were left as controls without using any resuscitation technique. A third group was hooked up to a perfusion system they developed called OrganEx (slow and continuous delivery of fluids). After six hours, they examined the condition of cells, tissues and the functioning of their vital organs.
“Not all cells die instantly, there are a series of events that take their time. It’s a process that you can intervene in, stop, and restore some cellular function.”
David Andrijevic, neuroscientist at Yale University School of Medicine
David Andrijevic, a neuroscientist at Yale University School of Medicine and co-author of the experiments, recalls that “not all cells die immediately, there is a series of events that take their time.” What they did was to take advantage of this time. “It’s a process that you can intervene in, stop and restore some cell function,” adds Andrijevic.
“OrganEx consists of two components,” Andrijevic said at a virtual meeting with journalists. “The first is a perfusion system, which is similar to cardiac and respiratory support systems connected to the circulatory system. The second part is a synthetic cellular fluid that is pumped and contains various elements optimized to promote cellular health, reduce cell death and inflammation throughout the body,” he explains. The basis of this fluid is a modified hemoglobin, the protein that carries oxygen.
After about twenty pigs were connected to OrganEx for six hours, they analyzed various parameters at the cellular level in the brain, lungs, heart, liver and kidneys. On virtually every metric, OrganEx outperformed ECMO. The scientists found that in many areas of the pig’s body, certain key cellular functions were active and even some organ functions were restored. They observed that neurons and astrocytes in two brain regions regained their pre-ischemia state. They also found electrical activity in the heart that maintained the ability to contract. In addition, they saw that the various organs reabsorb the glucose present in this artificial blood. Finally, they also found that at the genetic level, the cellular machinery restarted its repair mechanisms. But, and they wanted to emphasize this in both the published study and the conference, they did not see a recovery in overall brain activity. That is, they had not resuscitated the pigs, but they had resuscitated their organs.
“Basically, our findings underscore a previously overlooked ability of the large mammalian body to recover after blood flow has stopped.” And this could be used to increase organ availability for transplantation or to treat localized organ failure,” concludes Andrijevic.
“The technology holds great promise for our ability to preserve organs after they have been removed from a donor.”
Stephen Latham is Director of the Interdisciplinary Center for Bioethics at Yale.
His colleague Stephen Latham is director of the Yale Interdisciplinary Center for Bioethics and co-author of the study. For him, this work has and will have many applications. The shortest in terms of time are in the area of organ transplants. “I think the technology holds great promise for our ability to preserve organs after they’ve been harvested from a donor. You could take the organ and connect it to this perfusion system to transport it over a long distance for a long period of time to a recipient in need.” Given the very low temperature storage of the current systems, which poses a risk in recovery , these experiments kept the organs at temperatures of 36º to 37º.
Latham dismisses speculation about the possibility of connecting a human after cerebral, myocardial or renal ischemia: “This is very far from its use in humans. The goal here was to see if the use of perfusate [el fluido que crearon] could restore metabolic and cellular function in a variety of organs. And we have found that it is possible. But it doesn’t restore all function in all organs,” he recalls. Future applications in living humans would require, he adds, “that much more detail needs to be studied about the extent to which ischemic damage is reversed in different types of organs before even remotely contemplating doing such an experiment in a human.” “Human who has suffered anoxic damage”.
Neuroscientist Martin Monti from the University of California, Los Angeles (USA), who is not affiliated with the study, highlights what he thinks is most relevant from his findings: “Biological death is more like a cascade of dominoes, with an event that triggers death next, leading to an immediate transition. What is innovative about this technology is that this cascade can be stopped in some organs simply by restoring the right cellular environment and metabolic parameters.” According to Monti, if this is ever successfully translated to humans, the potential implications are enormous: “Thanks to increased organ viability, how many more lives could transplants save each year?”
“This study shows that our social convention about death, i.e. as the absolute end in black and white, is not scientifically valid.”
Sam Parnia, director of resuscitation and critical care research at New York University
New York University resuscitation and critical care research director Sam Parnia insists on Monti’s idea: “This study shows that our societal convention of death, that is, as an absolute end in black and white, is not scientifically valid. On the contrary, scientifically, death is a biological process that remains treatable and reversible hours after it occurs,” he told the Science Media Center (SMC).
The experiments on these dozens of 80-pound pigs, just a few months old, also prompt another deep reflection on whether OrganEx or a similar system will ever be used in humans. As Anders Sandberg, researcher at the Institute for the Future of Humanity at the University of Oxford (UK), puts it: “Ethically, this is [los experimentos] appears to be good news with no collateral issues. In the future, however, such methods could also make treatment immediately after a very serious stroke or trauma more effective: by saving patients who would otherwise have died, the number of available transplants could be reduced. This may still be good news, but there is a risk that it essentially saves people from dying rather than recovering them.” For Sandberg, there is an increasingly challenging ethical issue in statements to the SMC to state, ” when radical life support is just useless and as technology advances we will be able to find more ways to keep bodies alive despite not being able to resuscitate the person we really care about.”