The brain after a heart-lung machine: biomarkers and blood values, and what two of them showed in a new study in sheep

Back home, but your mind is somewhere else

The operation is behind you. You are home, the wound is closing and every day you walk a little further down the street. Yet in the kitchen, things keep going wrong. You walk into the kitchen and can no longer remember what you came for. You read the same paragraph in the newspaper twice and still cannot say what it was about. The name of someone from the neighbourhood, a name you have known for years, will not come. Your family says you seem far away, and you notice it yourself too: the heart was the part the surgeons needed, so why does it feel as if your head came home later than you did?

That gap between a body that recovers and a mind that lags behind is the subject of this background article. It is about the brain after heart surgery, about two proteins that can be measured in the blood, and about what a new animal study adds to what was already known.

You are not the only one

Heart care is part of life for a great many people. In the Netherlands, according to the RIVM on its VZinfo site, there were almost 52,000 hospital admissions in 2023 for a condition of the heart’s own blood vessels.⁠³ Not every admission ends in an operation, but the figure shows how common heart care is.

The operation itself takes a long time. For heart bypass surgery, the NHS writes in its 2025 guidance that the operation usually takes 3 to 6 hours.⁠⁴ The road back is longer still: according to the same 2025 NHS guidance, it usually takes 2 to 3 months to recover fully.⁠⁵ Those are months in which you are back home, and in which the questions in this article come up.

So if your head seems to be lagging behind your heart, you are in good company. The question researchers are asking is why, and whether something in the blood can show it.

Why the head can lag behind the heart

In some heart operations, a heart-lung machine takes over the work of the heart and lungs for a while. That saves lives, and it is also a major event for the rest of the body, the brain included. Research has long named two possible reasons for the mental fog afterwards: the brain getting too little oxygen, and an immune reaction in the brain itself.⁠¹

The brain has its own immune cells, the microglia. A 2024 review describes these cells as the brain’s first line of defence: the microglia clear away dead cells and direct immune responses, and the microglia probably play a central role in how the brain responds to the heart-lung machine.⁠⁶

What was known, and where it stopped

The Melbourne group behind the new study had looked at this before, in sheep. In work published in 2023, the heart-lung machine raised the immune system’s signalling substances in the blood more than anaesthesia and surgery alone did, and the microglia were activated in several areas of the outer layer of the brain, the cerebral cortex.⁠⁷

In people, one blood value had already drawn attention. In 167 patients having heart surgery, a protein called NfL was measured in the blood just before the operation, and again on the first day after it. Patients whose NfL rose after the operation often lost more points on thinking tests one year later.⁠²

That left a gap. How the changes in the brain unfold in the weeks after the machine, and how they relate to proteins in the blood, was poorly described, the authors of the new study write.⁠¹ A blood value is only useful as a window on the brain if you know what that value reflects, and when. That is the question the new study takes up.

A new study from Melbourne

The new work comes from a team of 24 researchers, with T. Furukawa as first author and Y.R. Lankadeva as senior author. Most of the researchers list the Florey Institute of Neuroscience and Mental Health and the University of Melbourne in Parkville, Australia, and all of the researchers list the Department of Intensive Care at Austin Health in Heidelberg, Australia. There were also co-authors from Monash University in Clayton, the Royal Melbourne Hospital and, in the Netherlands, Amsterdam UMC. The study was published on 10 October 2026 in the journal Intensive care medicine experimental, as a journal article and not as a preprint.⁠¹

The team did something that is impossible in people. The researchers connected sheep to a heart-lung machine, tracked the oxygen in the brain and two brain proteins in the blood, and then looked at the brain tissue itself, in the same animals, at two points in time: two days and four weeks after the operation. That way you can set a blood value next to what actually happened in the brain.⁠¹

Why this matters to you: the study does not tell you how your own brain will fare after an operation. What it adds is the timeline. In these sheep, the brain’s immune response after a heart-lung machine looked like a short wave rather than a lasting state, and meanwhile two proteins in the blood each rose and fell on a clock of their own. If blood values ever come to help track the brain after heart surgery, that timeline is the first thing you need to understand, and it is the idea the rest of this article explains.

Biomarkers and blood values as a window on the brain

One idea from this study is worth remembering, and it is easy to say and easy to misunderstand: a blood value is a snapshot of something that moves.

A biomarker is a substance you can measure, often in the blood, that tells you something about an organ you cannot look into directly. The brain sits behind the skull, and nobody takes a piece of it to see how a patient is doing after an operation. That is why researchers look for proteins that come from brain tissue and turn up in the blood. When such a protein rises, that can be a sign that something is happening in the brain. But a single blood sample only shows the level at the moment the needle goes in. If the protein rises and falls within a few hours, a sample taken a day later can miss the whole event.

The study looked at two such proteins. NfL, short for neurofilament light chain, is a building block of the long fibres of nerve cells. GFAP, short for glial fibrillary acidic protein, belongs to the astrocytes, the support cells of the brain. The researchers describe both as blood markers of the wearing down of nerve tissue.⁠¹

What the sheep showed

The study was carried out in 24 adult Merino ewes, female sheep. Sixteen were connected to a heart-lung machine, during which the large main artery leaving the heart was clamped for two hours. Eight of these sheep were then followed for 48 hours and eight for four weeks. Another eight sheep had no operation and formed the comparison group.⁠¹

First, the oxygen. The researchers tracked how much oxygen reached the brain tissue. The oxygen did not clearly change from its level before the machine, not in the first 48 hours and not over the four weeks either.⁠¹ Whatever happened in the brain, a lack of oxygen was therefore not the obvious cause in these animals.

Second, the brain’s immune cells. After 48 hours, the microglia in the front part of the cerebral cortex had a less rounded cell body than in the comparison sheep, and the authors read that change in shape as a sign that the cells were activated.⁠¹ The support cells went the same way: the share of brain tissue taken up by astrocytes with GFAP was clearly larger, about 17 per cent against 10 per cent in the comparison sheep.⁠¹ After four weeks, neither measurement still clearly differed from the comparison sheep.⁠¹

Then the blood. Two examples show why the moment of measuring decides everything here.

Example one is GFAP, the fast signal. In the blood, GFAP was highest right at the end of the time on the heart-lung machine, with a median of about 14.4 picograms per millilitre against about 3.0 before the operation, almost five times as high. After 48 hours the GFAP level was back to normal.⁠¹ Think about what that means. A GFAP level taken two days after the operation would have looked perfectly ordinary, while at that same moment the brain tissue was still showing activated immune cells.

Example two is NfL, the slower signal. NfL rose from a median value of about 138 picograms per millilitre before the operation to about 198 after 48 hours, a clear rise.⁠¹ The summary reports no NfL value at the end of the period on the machine. What the summary does show is that two proteins from the same brain, measured in the same animals, followed a different clock: one protein went up and down within two days, the other was still raised on day two.

Put the two examples side by side and the idea becomes concrete. If you ask one blood sample “has the brain been affected?”, the answer depends on which protein you measure and at what hour you measure it. That is why the authors are cautious. The authors call the link between these changes in the brain and the blood values GFAP and NfL preliminary evidence of an association that needs further research.⁠¹

What people in healthcare say

The researchers did not start with sheep. The starting point was patients. In 2025 the senior author put it like this, speaking about the group’s MEGA-HEART research project and so not about this article:

Many people wake up after life-saving heart surgery confused, forgetful and restless.

Yugeesh Lankadeva, professor and lead researcher of the MEGA-HEART project, The Florey Institute of Neuroscience and Mental Health⁠⁸

An intensive care doctor who once had heart surgery describes the same thing from the hospital bed:

After the operation, you are a different person for a while.

Simon Iles, intensivist and former heart surgery patient, Royal Melbourne Hospital⁠⁹

And the Heart Foundation in Australia hears it from patients:

Anecdotally, people often complain that their mental abilities are ‘not quite right’.

Garry Jennings, Professor and Chief Medical Adviser, Heart Foundation (Australia)⁠¹⁰

The sheep study gives those words a biological trail to follow, nothing more.

What the study did not show

• It is an animal study. Sheep are not people, and the summary reports no thinking or memory tests in the animals. Whether these changes in the brain went together with confusion in the sheep is not reported.⁠¹
• It is small: eight sheep per group, and only female sheep.
• The tissue measurements are only reported for the front part of the cerebral cortex.
• Different animals were examined at 48 hours and at four weeks, so no single sheep was followed over time in the brain tissue.
• It shows a link between changes in the brain and blood values across groups, not that a blood value reliably reflects the brain of one individual. The authors call it preliminary.⁠¹
• In people, the earlier study of 167 patients points in a similar direction for NfL, but that study measured thinking scores, not brain tissue.⁠²
• BioProfile read the abstract through the PubMed record; the full text was not opened, so details beyond the abstract are not reported here. No press release about this article was found.⁠¹

What you can do now

None of these three directions is a prescription.

First: if you are facing heart surgery, or someone close to you is, know that a foggy head afterwards is something researchers take seriously and study. Before you go home, ask the care team what it sees in its own patients in the weeks after the operation, and who you can call if something worries you.

Second: if you or someone close to you is confused after an illness or an operation, that is a reason to contact your GP or another doctor. Thuisarts writes that it happens mainly in older people.⁠¹¹

Third: look at the longer road. Whether you age well is not decided by one operation, and blood values are only one window onto it. The open question is how you are ageing now, and where you would start. A free BioProfile healthy ageing scan gives you a starting point for that question, as self-insight for your own choices. The scan is not a diagnosis.