In 2019, neuroscientists and doctors from Yale University (USA) succeeded in recovering part of the brain functions of a pig that had been slaughtered four hours earlier at an abattoir. Now this same group has repeated the feat, but in all the vital organs of several pigs that have been dead for an hour. The research, recently published in Naturerelied on a complex injection system of a kind of superblood 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 is set in motion: lack of blood supply (ischemia) involves the absence of oxygen and other essential elements leading to the death of cells, tissues, organs and the whole organism. In this investigation, the scientists caused cardiac arrest in dozens of pigs (they had been previously anesthetized). After an hour without a blood supply, i.e. dead, they were divided into several study groups: some were connected to a life support system used in severe cases in which the heart and lungs cease to function (ECMO, for its English acronym for extracorporeal membrane oxygenation). Others were left as a control group, without applying any resuscitation techniques. A third group was connected to an infusion system (slow and continuous introduction of liquids) designed by them and called OrganEx. After six hours, they studied the state of cells, tissues and the functioning of their vital organs.
“Not all cells die immediately, there is a series of events that take their time. It is a process in which you can intervene, stop and restore certain cellular functions”
David Andrijevic, neuroscientist at Yale University School of Medicine
David Andrijevic, 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 take advantage of this period. “It’s a process in which you can intervene, stop and restore certain cellular functions,” adds Andrijevic.
“OrganEx is made up of two components,” Andrijevic said in a virtual meeting with reporters. “The first is a perfusion system similar to cardiac and respiratory support systems that connects to the circulatory system. The second part is a synthetic cellular fluid that is pumped and contains different elements optimized to support cellular health, reduce cell death and inflammation throughout the body,” he explains. The basis of this fluid is modified hemoglobin, the protein that carries oxygen.
After connecting about 20 pigs 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. Scientists found that certain key cell functions were active in many areas of the pigs’ bodies, and even some organ functions had been restored. Thus, they observed that neurons and astrocytes in two regions of the brain returned to their pre-ischemic state. They also detected electrical activity in the heart, which retained the ability to contract. In addition, they saw that the various organs recapture the glucose present in this artificial blood. Finally, they also discovered that at the genetic level, the cellular machinery restarts its repair mechanisms. But, and this is what they wanted to emphasize both in the published study and in the conference, they did not detect a recovery in general brain activity. That is to say, they had not resuscitated the pigs, but they had resuscitated their organs.
“Fundamentally, our findings highlight a previously overlooked ability of large mammalian bodies to recover after blood flow has ceased. And it could be used to increase organ availability for transplants or treat localized organ failure,” concludes Andrijevic.
“The technology holds great promise for our ability to preserve organs after removing them from a donor”
Stephen Latham is director of the Yale Interdisciplinary Center for Bioethics.
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 closest in time are in the field of organ transplants. “I think the technology holds great promise for our ability to preserve organs after removing them from a donor. You can take the organ and hook it up to this infusion system so that you can transport it over a long distance for a long time to a recipient in need. Faced with the conservation at very low temperature of the current systems, which involves a risk during their recovery, these experiments have maintained the organs at temperatures of 36º to 37º.
On the possibility of connecting a human after cerebral, myocardial or renal ischemia, Latham cut short speculation: “It is very far from its use in humans. The objective here was to see if the use of perfusate [el fluido que crearon] could restore metabolic and cellular function in a wide range of organs. And we have discovered that it is possible. But this does not restore all functions in all organs,” he recalls. Future application in living humans would, he adds, require “much more detail to study about the extent to which ischemic damage is repaired in different types of organs before one even thinks of trying an experiment.” like this in a human.” human who has suffered anoxic damage”.
Neuroscientist from the University of California, Los Angeles (USA) Martin Monti, unrelated to the study, points out what he considers most relevant of his results: “Biological death is more like a cascade of dominoes , with an event that triggers the next, which has an instantaneous transition. What is innovative in this technology is that this cascade can be stopped in certain organs simply by restoring the correct cellular environment and metabolic parameters. According to Monti, the potential implications, if this is ever successfully translated into humans, are enormous: “How many more lives could be saved by transplantation each year through increased organ viability?”
“This study shows that our social convention of death, that is, as an absolute black and white end, is not scientifically valid”
Sam Parnia, director of resuscitation and critical care research at New York University
The director of research in resuscitation and intensive care at New York University, Sam Parnia, insists on the idea pointed out by Monti: “This study shows that our social convention on death, that is to say as a absolute end in black and white, is not scientifically sound. On the contrary, scientifically, death is a biological process that remains treatable and reversible for hours after it occurs,” he explained to the Science Media Center. (SMC).
The experiments with these dozens of 35-kilogram, month-old pigs also prompt another deep thought if OrganEx or a similar system is ever used in humans. Anders Sandberg, researcher at the Institute for the Future of Humanity at the University of Oxford (United Kingdom), asserts: “Ethically, this [los experimentos] seems like good news with no side issues. In the future, however, such methods could also make treatment given right after a stroke or very severe trauma more effective: by saving patients who would otherwise have died, this could reduce the number of transplants available. This may still be good news, but there is a risk that it will essentially prevent people from dying rather than getting them cured.” For Sandberg, in statements to the SMC, there is one more ethical problem. more difficult to determine “when radical life support is simply unnecessary and as technology advances we will be able to find other ways to keep bodies alive despite being unable to revive the person who we really care about.
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