New pig study challenges definition of "brain death"

In a new article published on April 17 in Nature, researchers describe an artificial perfusion system called BrainEx which can restore some structural and functional properties in the brains of pigs up to four hours after their death (1).

This interesting study challenges the concept of "brain death" – an irreversible brain injury resulting in a total loss of brain function – which for many years has been a gray area between science and medicine. The current belief is that the mammalian brain is irreversibly damaged only minutes after blood stops circulating.

In the majority of countries, two situations allow a person to be declared legally dead: irreversible loss of all brain functions (brain death) or irreversible loss of any circulatory function (circulatory death).

Researchers at Yale University developed the BrainEx system for determining whether certain brain functions can, in fact, be restored – at least partially – after an extended post-mortem interval (time elapsed since death). The system consists of a computerized network of pumps, heaters and filters that control the flow and temperature of an exclusive perfusate.

Some brain functions restored in pigs, but not all

To test their system, the scientists took 24 pig brains and connected them to the system four hours after killing. They discovered that a pulsatile infusion device could restore and maintain circulation and even keep certain cells alive in the brain.

However, they could not detect any neuronal activity that was supposed to be necessary for consciousness, and the system only restored circulation in small blood vessels and capillaries, but not in large arteries. In addition, the experiment being completed after six hours, scientists do not know how long the system will be able to maintain these functions.

Nevertheless, new findings suggest that under certain conditions, the mammalian brain may possess the ability to restore itself – particularly microcirculation and molecular and cellular activity – several hours after death. The new technology could not only help researchers develop new treatments for brain damage, but could also be used for future studies on the intact mammalian large brain.

However, as Nature This study could also exacerbate existing tensions in the medical field as it raises a number of ethical issues that have long been debated. Including how long should paramedics try to resuscitate? This is currently the subject of various directives in Europe and elsewhere.

When to call closes

Bioethicists and medical practitioners often fear that patients will be placed too early in organ recovery systems – there are currently large differences between countries in morally and legally acceptable practices. For example, the extracorporeal membrane oxygenation system (ECMO) used in Europe limits blood flow to the brain. Many argue that, in some cases, brain function could eventually be found.

Researchers are far from able to restore brain function in "brain deaths". But such techniques could ensure that patients someday become candidates for brain resuscitation instead of organ donation. This makes it more difficult to find the necessary organs for transplantation.

So, when is it appropriate to stop trying to save someone's life to try to save their organs for a transplant? The question is complex and it seems that the answer is not clear in the near future.

(1) Vrselja, Z. et al. Restoration of the cerebral circulation and cellular functions post mortem hours. Nature (2019). DOI: 10.1038 / s41586-019-1099-1