HERE’S a fact that might chill the cockles of your heart: if your ticker stops, you have less than 5 minutes to get it going again before your brain experiences irreversible damage. But there could soon be a way to open that window much wider, thanks to a technique that rapidly cools the body to exploit the life-saving powers of another notorious killer: hypothermia.
It may seem paradoxical, but it all boils down to simple chemistry. You might think of ourself as a biological organism, but at a baser level you are chemical. Chemistry governs the function of your cells, senses, digestion and even your thoughts.
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As temperatures fall, chemical reactions slow down. That’s why it isn’t good to get too cold: if you lose too much heat, you slip into hypothermia. Remove enough heat and the reactions eventually shut off completely – a state known to biologists as death.
But here’s the twist: sometimes, especially if death is an imminent danger, cold can be a lifesaver. “Hypothermia has huge benefits,” says Renaud Tissier of the National Veterinary School of Alfort, France.
To harness these, Tissier and his collaborators have built a machine that plunges your body to frigid temperatures in a matter of minutes. How does it work? Take a deep breath and prepare to gag: by pumping a chilled liquid into your lungs.
“To harness hypothermia, the machine pumps chilled liquid into the lungs”
We have known about the therapeutic effects of cooling for a long time. Hippocrates was a fan, suggesting that a wounded soldier fared better if quickly covered in snow. And a few 20th-century studies suggested that head injuries, in particular, cause less damage if the patient is cooled. But effective cooling has always remained difficult. Ice packs or gel pads on the body to stop the processes set in motion by an injury or a heart attack. And that is simply too long.
Take heart attacks, for example. If your heart stops while you are shopping or on the squash court, say, you are in immediate danger. “Within 3 to 5 minutes the brain suffers permanent and irreversible damage,” says , who studies emergency care at the University of the West of England in Bristol.
With the heart stopped, no blood is being pumped around the body. “The brain requires a supply of oxygen and glucose to work, and if you cut those off, the neurons start to die very quickly,” says Benger. Without oxygen, your body switches to anaerobic metabolism, which causes a cascade of harmful biochemical effects. Mitochondria, which produce the energy your cells need to function, shut down and die. Fluid floods into the brain. And your DNA can be damaged, meaning that – even if you survive – cell replication is disrupted too. The longer it goes on, the worse the damage is likely to be.
This cascade is what’s behind the frightening heart attack statistics. Only 15 per cent of stopped hearts start again, almost always because of prompt medical intervention. But they usually start too late. “The majority of those people still don’t survive,” says Benger. The exact numbers depend on where you live and other factors, but in the UK only about alive. Even among those who do, .
But drop the body’s temperature by 1°C and cerebral metabolism falls by between 6 and 10 per cent, reducing the rate of those harmful biochemical effects. Dropping it by 3 or 4°C buys a lot of time.
Tissier first began pondering whether such a drop could be practicable in 2005 while on a fellowship studying treatments for heart attacks at the University of South Alabama. Down the corridor, medical engineers James Downey and were working on liquid ventilation to relieve breathing problems that arise in preterm babies. The surfactants that keep adult lungs lubricated aren’t present in some premature babies, so their lungs can stick together. Parker and Downey were investigating whether a liquid known as perfluorocarbon (PFC) could help.
We have known since the 1960s that PFC is excellent at holding dissolved oxygen in a way that the lungs can absorb (see “Deep breathing”). What we have never perfected is how to get the liquid in and out of the lungs. On each breath, the oxygenated fluid needs to be pumped into the lungs, and the carbon dioxide-rich fluid has to be pumped out again. But if the pressure is wrong, the trachea can collapse or the lungs can burst – or fail to fill at all. “You need very accurate measurement of the lung pressures and the filling pressure to calculate the ideal flow rate,” Tissier says.
Tissier couldn’t help but notice that in Parker and Downey’s set-up the PFC had to be warmed to avoid reducing body temperature. “It gave me the idea to use the lung as a heat exchanger,” he says. The lungs have an enormous surface area, so filling them with cool liquid would be an effective way to refrigerate the body fast, from the inside out.
Parker and Downey had invented a pumping machine, to get the liquid into the lungs. So they and Tissier went to work on adapting it for cooling, by fitting heating controls and pressure gauges to accurately monitor the temperature and flow of the liquid. Once ready, they tried it out on anaesthetised rabbits.
“We found that the heart and brain were cooled very, very rapidly – within 2 minutes,” Tissier says. Further experiments showed that rapid cooling by liquid ventilation with PFC could halt the progress of a heart attack in rabbits and reduce any neurological damage.
Tissier then had to return to France; it was the end of his fellowship. And he soon realised that he needed a new, more delicately tuneable machine if he was ever to try human experiments. To create one, he collaborated with a group of researchers including Étienne Fortin-Pellerin and Philippe Micheau at Sherbrooke University in Canada, who were also interested in using liquid ventilation to aid premature babies.
Over the past few years they have been tweaking the pump, making it responsive enough to correct tiny fluctuations in pressure. Last year, Tissier and his team tested it on six anaesthetised lambs, filling their lungs with PFC at 12°C at carefully controlled pressures. The lambs’ femoral artery temperature fell from the normal 39°C to 33°C – where the harmful biochemical reactions are significantly slowed – within 7 minutes. They also performed an experiment in which they anaesthetised and induced heart attacks in rabbits, some of which were then cooled with the liquid ventilator while others weren’t. The cooled rabbits had .
The Sherbrooke researchers are excited about the improved ventilator because it helps their own research focus of premature babies. Tissier, though, finds the result exciting for its potential in treating people who have heart attacks. “We’ll need to anaesthetise and intubate them, but we’ve shown that we can probably cool an adult human in 15 to 20 minutes without any after effects,” he says. “This can provide much more benefit than ways of cooling that take 1 or 2 hours.”
The team says that the technique is now ready to be tried in people, and the next step is to carry out a clinical trial. So, will we soon see liquid ventilators in emergency rooms around the world?
Benger isn’t convinced that the method will be possible at the sharp end of a heart attack, mainly because of the time it takes to set up and the need for wide rollout of the necessary equipment. He would rather see money and effort spent on public education. “The best thing we can do is to train everybody to do resuscitation, call an ambulance and get a defibrillator to the patient,” he says. “It’s a lot cheaper than messing about with complex cooling technology, and will save a lot more lives.”
“Liquid ventilation slowed the harmful effects of a heart attack in 7 minutes”
But he thinks the chilling pump could be useful for people with trauma injuries such as gunshot wounds. In such cases, the heart isn’t stopped but circulation is compromised, so doctors have a little more time to put them on a life-support device. “You can make their metabolism fall and do the necessary repair work while they’re resting,” says Benger. Another way to do this is to replace a person’s blood with a cold saline solution, which chills them to 10°C, at which point metabolism stops almost entirely. But with that technique yet to be proven safe in clinical trials, liquid ventilation – arguably a gentler option – is worth pursuing.
Tissier is still confident that slowing chemistry will make a difference to the cardiac arrest statistics that plague modern medical care, but it might have even greater utility with gunshot or knife wounds. So far, he points out, it hasn’t been possible to chill an adult human to 33°C in less than 2 hours, so the advantages of 15-minute cooling are yet to be seen. When they are, he says, it will be the start of something very cool indeed.
Deep breathing
The film director James Cameron brought liquid ventilation to the silver screen in his 1989 film The Abyss. It features a team of divers working to recover a sunken vessel from the deep ocean. At this depth, the pressure is so high it would collapse a diver’s lungs. To avoid that, one diver breathes in oxygen- infused perfluorocarbon (PFC), a liquid that can withstand the pressures and hold the lungs open.
Back in reality, could this technique ever help divers venture below 100 metres, the point at which the lungs generally collapse? The principle makes sense: PFC can hold three times as much oxygen as human blood, so the gas would pass into the bloodstream. And through the 1960s and 70s, liquid ventilation experiments were partially successful. Animal studies showed that rodents, cats and dogs could breathe PFC for extended periods.
They didn’t, however, emerge unscathed. There was usually damage to the lungs and trachea, and once the animals were breathing air again it became clear that they had been poisoned from not being able to get rid of the carbon dioxide quickly enough. In a 1968 Scientific American article, Johannes Kylstra of Duke University Medical Centre described experiments on 22 dogs, only seven of which survived.
Nonetheless, other liquid ventilation researchers suggested that the technique “, undersea oxygen support facilities, and medical research”. This was an age when submarine fleets were essential to the delicate balance of the cold war, so finding ways for crews to escape a sunken craft – or for divers to rescue sensitive materials left on board – seemed a good idea.
Kylstra got as far as human experiments. His first involved a diver called Francis J. Falejczyk, who allowed one lung to be filled with oxygenated saline. He said he felt no difference from breathing air in both lungs. There are rumours that Kylstra later tried full liquid breathing out on US Navy SEALs.
The sticking point has always been getting the liquid in and out of the lungs. PFC is too heavy for the diaphragm to move it. “I heard that Navy SEALs would sometimes break their ribs trying to expel the liquid,” says Renaud Tissier of the National Veterinary School in Alfort, France. Instead, he has been building a pump to do the hard work. Could a waterproof version of his pump be modified to serve as a deep diving rig? Possibly – but not a terribly practical one.
This article appeared in print under the headline “Cold hearted”
