Speaking of Research
It is estimated that 20 Americans die each day because of the unavailability of organs for transplant. Now, scientists are hoping to solve the organ crisis by researching the question: Can death be reversed? The thought-provoking study by researchers at Yale School of Medicine begins to question the inevitability of death. The team, led by neuroscientist Nenad Sestan, reported last week in Nature that the function of specific molecular and cell processes could be restored in pigs, 1 hour after the animals had died by cardiac arrest.
The study built upon previous findings, in which the team was able to restore circulation and cellular activity in isolated pig brains, using BrainEx, a perfusion technology which provided the brains with a solution designed to provide a brain-specific chemical environment. In the new study published in Nature, the researchers wanted to translate this technology to the whole body, a challenging feat because perfusion of the whole body has additional complications, such as coagulation, immune response and multisystem physiological problems.
What did the researchers do?
Based on the BrainEx principles, the researchers designed a new perfusion system for whole-body perfusion, called OrganEx, consisting of a pump device, a sensor system and a special mixture of the animal’s own blood and chemical solution. The team obtained pigs from a local farm breeder and induced cardiac arrest while the animals were anesthetized and on a ventilator. After cardiac arrest was confirmed, they removed the animals from the ventilator. One hour after the pigs died, the anesthesia and ventilation restarted. The researchers connected some of the pigs to OrganEX via a femoral vein or artery. They perfused the body for 6 hours, while controlling the perfusion of organs in real time. They compared the OrganEX group to 3 control groups left without intervention for several hours and another experimental group, connected to another perfusion system called ECMO (extracorporeal membrane oxygenation system), a machine used in hospitals to help patients whose lungs and/or heart have stopped functioning. While the ECMO system failed, the organEX system successfully restored systemic circulation and normalized physiological and metabolic parameters across the pigs’ whole body. As a result, the OrganEx group did not display postmortem rigidity or the pale color characteristic of a dead body. These remarkable findings demonstrate that cellular death can be halted and recovery achieved, even after prolonged cessation of blood flow in a large mammal. However, it is important to clarify that whereas organ function in the body was revived, reviving brain function was not attempted in the study.
What are the potential applications of the technology?
The technology could lead to substantial improvement in organ transplantation, as OrganEX could extend the viability of an organ after a person dies, thus increasing organ availability for transplantation. The results are also promising for clinical resuscitation science, but the authors caution that future studies and many more steps in the process need to be completed to include the recovery of brain function.
Some ethical issues
Although the brains lacked electrical activity, jerking of head and neck was observed, and only in the OrganEx pigs, after animals were injected with an agent to visualize their brains. Although it is possible that the movements were initiated without the involvement of the brain, the authors acknowledge that thoughtful evaluations are needed, in concert with ethical oversight, to better understand these effects.
Andrijevic, D. et al. Nature https://doi.org/10.1038/s41586-022-05016-1 (2022).