When someone’s heart stops, doctors rush to restart it. But even if they succeed, the brain often pays the price. Just a few minutes cut off from the blood supply is enough to cause irreversible damage to a patient’s brain.
Now, a new study suggests that an unlikely hero — the liver — may protect the brain from severe damage after cardiac arrest. Researchers in China have managed to revive brain activity in pigs nearly an hour after circulation ceased. This achievement was made possible by integrating the liver into the life support system.
These findings could expand the critical window for resuscitating cardiac arrest patients, which may eventually improve human survival rates.
Studying Cardiac Arrest
Cardiac arrest shuts off blood flow to the brain, leading to a drop in oxygen and nutrients, a process known as ischemia. Within minutes, brain cells start dying. This is why doctors have only a narrow window for successful resuscitation after cardiac arrest. Sudden cardiac arrest affects hundreds of thousands of people yearly in Europe and the U.S., with survival rates remaining low.
But new research, led by Xiaoshun He from Sun Yat-Sen University in China, has shown that the liver may play a surprising role in extending this window.
In their study, the researchers used the brains of 17 Tibetan minipigs to explore the effects of liver ischemia — when the liver is deprived of blood — on brain recovery after cardiac arrest. The pigs’ brains were harvested and connected to brain normothermic machine perfusion (NMP), a life support system.
The pig brains were divided into different groups, each subjected to varying levels of ischemia. One group, for instance, involved the pig’s liver connected to the NMP, while another group experienced brain ischemia alone.
The researchers simulated cardiac arrest conditions to investigate how these animals’ brains responded with and without liver support during resuscitation efforts. Each pig brain was subjected to 30 minutes of warm ischemia. Then the researchers attempted to revive the organs using a machine-based perfusion system.
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The Brain-Liver Connection
The researchers found stark differences in brain recovery depending on whether the liver was included in the perfusion setup. Without liver support, the brains showed clear signs of distress: swelling, increased cellular damage, and loss of electrical activity after a few hours of perfusion. This outcome was typical of brains suffering from ischemia-reperfusion injury, where tissues, after being deprived of oxygen, are overwhelmed by oxidative stress upon reintroduction of blood flow.
On the other hand, brains connected to the liver-assisted perfusion system fared significantly better. In these cases, the liver seemed to buffer the brain from the worst damage. Not only was brain swelling less pronounced, but electrocortical activity — measured by EEG — was also restored and maintained for up to 6 hours. This electrical activity, which involved alpha and beta waves, is a marker of functional brain activity.
The liver-assisted brains also showed lower levels of the S100-β protein, a marker for neural injury, compared to brains perfused without liver support. Neurons in key areas like the cortex and hippocampus were visibly healthier, with less tissue damage.
All of this suggests that the liver played a protective role during the reperfusion process.
Why Did the Liver Make Such a Difference?
The liver’s role in protecting the brain seemed to stem from its metabolic and anti-inflammatory functions. When the liver was present in the perfusion circuit, it continued producing vital metabolic molecules. These include ketone bodies, which the brain can use as an alternative energy source when glucose is scarce.
Moreover, the researchers found that genes related to cell death and immune responses were more active in brains without liver support. In contrast, brains perfused with a liver showed gene expression patterns that were more conducive to the brain’s survival and recovery. These findings suggest that the liver moderates inflammation in the brain, helping to reduce secondary injury caused by immune cell infiltration.
A Window of Opportunity for Resuscitation
In their study, the researchers also tested how long the brain could endure warm ischemia before irreversible damage occurred. Remarkably, when the liver was present, brains could recover even after 50 to 60 minutes without blood flow. This finding contrasts with traditional views that the brain can only tolerate 5 to 8 minutes of ischemia before suffering permanent damage.
These findings underscore the liver’s potential role in post-cardiac arrest therapies. While much of the focus in resuscitation has been on the heart and brain, the liver shouldn’t be ignored.
Artificial liver support systems, the kind many patients with liver failure already use, could one day be adapted to protect the brain during and after cardiac arrest.
These results not only challenge existing ideas about the brain’s vulnerability to oxygen deprivation but also offer new hope for therapies that could improve the survival and recovery of cardiac arrest patients.
The findings were reported in the journal EMBO Molecular Medicine.
