Scientists have revived activity in the brains of pigs for almost an hour after circulation had stopped. In some cases, functionality was maintained for hours through a surprising discovery by researchers in China.
This achievement represents a major step forward in finding how to restore brain function after a patient has suffered a sudden cardiac arrest. It suggests that doctors may be able to extend the brief window for successful resuscitation of patients after cardiac arrest.
Cheating? Incorporating the patient’s undamaged liver — the organ the body uses to clean its own blood — into the life support system used to revive the brain after time has passed.
Sudden cardiac arrest causes many problems in the body due to the rapid interruption of blood circulation. The subsequent loss of circulation to parts of the body is called ischemia, and when it occurs in the brain, it can cause serious and irreversible damage within minutes. This is why the resuscitation window for cardiac arrest is so short.
Multi-organ ischemia is known to play a role in the brain’s ability to recover after a cardiac arrest, but individual organs have not been fully investigated.
In recent years, scientists have used pig models to test methods for limiting brain damage. Supervised by doctor Xiaoshun He of Sun Yat-Sen University in China, a team of scientists turned to the animal to try and understand the role of the liver in brain recovery after ischemia due to cardiac arrest.
Using 17 lab-grown Tibetan minipigs, the team compared the involvement of a liver in the loss of circulation. In one set of experiments, two groups of pigs were subjected to brain ischemia for 30 minutes; One of the groups also underwent liver ischemia and the other did not. Meanwhile, a control group did not undergo ischemia.
When the pigs were euthanized and their brains were examined, the control group obviously had the least brain damage; but the group that had not undergone liver ischemia showed significantly less brain damage than the group that had.
The next phase of the research involved trying to incorporate an intact liver into the life support system by reviving a brain that had been completely removed from a euthanized pig. This is unlikely to be a scenario used to treat humans, but it helps scientists understand the windows in which resuscitation may be viable.
The basic life support system includes an artificial heart and lungs to help pump fluids through the brain. For one group, pig liver was integrated into the system, known as liver-assisted normothermic brain perfusion.
First, the brain was connected to life support systems 10 minutes after the start of the life support procedure. For the liver-free system, electrical activity in the brain appeared within half an hour before declining over time.
The team also experimented with different delays, connecting the brain to the liver-assisted system at intervals of 30 minutes, 50 minutes, 60 minutes and 240 minutes. The longest interval that showed the most promise was 50 minutes after being deprived of blood: the brain resumed electrical activity and remained in that state for six hours until the experiment was closed.
Surprisingly, in brains that had been starved of oxygen for 60 minutes, activity returned for only three hours before fading, suggesting a critical interval in which resuscitation can be successful with the addition of a functioning liver.
These results, the researchers say, suggest that the liver plays an important role in the development of brain damage after cardiac arrest. The findings suggest new avenues for brain injury research and may hopefully improve survival rates and recovery outcomes for human patients in the future.
The research was published in EMBO Molecular Medicine.