This Soft Artificial Heart May One Day Shorten the Heart Transplant List

ETH Zurich
ETH Zurich

If the heart in the Functional Materials Laboratory at ETH Zurich University were in a patient in an operating room, its vital signs would not be good. In fact, it would be in heart failure. Thankfully, it's not in a patient—and it's not even real. This heart is made of silicone.

Suspended in a metal frame and connected by tubes to trays of water standing in for blood, the silicone heart pumps water at a beat per second—a serious athlete's resting heart rate—in an approximation of the circulatory system. One valve is leaking, dripping onto the grate below, and the water bins are jerry-rigged with duct tape. If left to finish out its life to the final heartbeat, it would last for about 3000 beats before it ruptured. That's about 30 minutes—not long enough to finish an episode of Grey's Anatomy

Nicolas Cohrs, a bioengineering Ph.D. student from the university, admits that the artificial heart is usually in better shape. The one he holds in his hands—identical to the first—feels like taut but pliable muscle, and is intact and dry. He'd hoped to demonstrate a new and improved version of the heart, but that one is temporarily lost, likely hiding in a box somewhere at the airport in Tallinn, Estonia, where the researchers recently attended a symposium.

Taking place over the past three years, the experimental research is a part of Zurich Heart, a project involving 17 researchers from multiple institutions, including ETH, the University of Zurich, University Hospital of Zurich, and the German Heart Institute in Berlin, which has the largest artificial heart program in Europe.

A BRIDGE TO TRANSPLANT—OR TO DEATH

Heart failure occurs when the heart cannot pump enough blood and oxygen to support the organs; common causes are coronary heart disease, high blood pressure, and diabetes. It's a global pandemic, threatening 26 million people worldwide every year. More than a quarter of them are in the U.S. alone, and the numbers are rising.

It's a life-threatening disease, but depending on the severity of the condition at the time of diagnosis, it's not necessarily an immediate death sentence. About half of the people in the U.S. diagnosed with the disease die within five years. Right now in the U.S., there are nearly 4000 people on the national heart transplant list, but they're a select few; it's estimated that upwards of 100,000 people need a new heart. Worldwide, demand for a new heart greatly outpaces supply, and many people die waiting for one.

That's why Cohrs, co-researcher Anastasios Petrou, and their colleagues are attempting to create an artificial heart modeled after each patient's own heart that would, ideally, last for the rest of a person's life.

Mechanical assistance devices for failing hearts exist, but they have serious limitations. Doctors treating heart failure have two options: a pump placed next to the heart, generally on the left side, that pumps the blood for the heart (what's known as a left ventricular assist device, or LVAD), or a total artificial heart (TAH). There have been a few total artificial hearts over the years, and at least four others are in development right now in Europe and the U.S. But only one currently has FDA approval and CE marking (allowing its use in European Union countries): the SynCardia total artificial heart. It debuted in the early '90s, and since has been implanted in nearly 1600 people worldwide.

While all implants come with side effects, especially when the immune system grows hostile toward a foreign object in the body, a common problem with existing total artificial hearts is that they're composed of hard materials, which can cause blood to clot. Such clots can lead to thrombosis and strokes, so anyone with an artificial heart has to take anticoagulants. In fact, Cohrs tells Mental Floss, patients with some sort of artificial heart implant—either a LVAD or a TAH—die more frequently from a stroke or an infection than they do from the heart condition that led to the implant. Neurological damage and equipment breakdown are risky side effects as well.

These complications mean that total artificial hearts are "bridges"—either to a new heart, or to death. They're designed to extend the life of a critically ill patient long enough to get on (or to the top of) the heart transplant list, or, if they're not a candidate for transplant, to make the last few years of a person's life more functional. A Turkish patient currently holds the record for the longest time living with a SynCardia artificial heart: The implant has been in his chest for five years. Most TAH patients live at least one year, but survival rates drop off after that.

The ETH team set out to make an artificial heart that would be not a bridge, but a true replacement. "When we heard about these problems, we thought about how we can make an artificial heart that doesn't have side effects," he recalls.

USING AN ANCIENT TECHNIQUE TO MAKE A MODERN MARVEL

Using common computer assisted design (CAD) software, they designed an ersatz organ composed of soft material that hews closely to the composition, form, and function of the human heart. "Our working hypothesis is that when you have such a device which mimics the human heart in function and form, you will have less side effects," Cohrs says.

To create a heart, "we take a CT scan of a patient, then put it into a computer file and design the artificial heart around it in close resemblance to the patient's heart, so it always fits inside [the body]," Cohrs says.

But though it's modeled on a patient's heart and looks eerily like one, it's not identical to the real organ. For one thing, it can't move on its own, so the team had to make some modifications. They omitted the upper chambers, called atria, which collect and store blood, but included the lower chambers, called ventricles, which pump blood. In a real heart, the left and right sides are separated by the septum. Here, the team replaced the septum with an expansion chamber that is inflated and deflated with pressurized air. This action mimics heart muscle contractions that push blood from the heart.

The next step was to 3D-print a negative mold of the heart in ABS, a thermoplastic commonly used in 3D printing. It takes about 40 hours on the older-model 3D printers they have in the lab. They then filled this mold with the "heart" material—initially silicone—and let it cure for 36 hours, first at room temperature and then in an oven kept at a low temperature (about 150°F). The next day, they bathed it in a solvent of acetone, which dissolved the mold but left the printed heart alone. This process is essentially lost-wax casting, a technique used virtually unchanged for the past 4000 years to make metal objects, especially bronze. It takes about four days.

The resulting soft heart weighs about 13 ounces—about one-third more than an average adult heart (about 10 ounces). If implanted in a body, it would be sutured to the valves, arteries, and veins that bring blood through the body. Like existing ventricular assist devices and total artificial hearts on the market, it would be powered by a portable pneumatic driver worn externally by the patient.

FROM 3000 TO 1 MILLION HEARTBEATS

In April 2016, they did a feasibility test to see if their silicone organ could pump blood like a real heart. First they incorporated state-of-the-art artificial valves used every day in heart surgeries around the world. These would direct the flow of blood. Then, collaborating with a team of mechanical engineers from ETH, they placed the heart in a hybrid mock circulation machine, which measures and simulates the human cardiovascular system. "You can really measure the relevant data without having to put your heart into an animal," says Cohrs.

Here's what the test looked like.

"Our results were very nice," Cohrs says. "When you look at the pressure waveform in the aorta, it really looked like the pressure waveform from the human heart, so that blood flow is very comparable to the blood flow from a real human heart."

Their results were published earlier this year in the journal Artificial Organs.

But less promising was the number of heartbeats the heart lasted before rupturing under stress. (On repeated tests, the heart always ruptured in the same place: a weak point between the expansion chamber and the left ventricle where the membrane was apparently too thin.) With the average human heart beating 2.5 billion times in a lifetime, 3000 heartbeats wouldn't get a patient far.

But they're making progress. Since then, they've switched the heart material from silicone to a high-tech polymer. The latest version of the heart—one of which was stuck in that box in the Tallinn airport—lasts for 1 million heartbeats. That's an exponential increase from 3000—but it's still only about 10 days' worth of life.

Right now, the heart costs around $400 USD to produce, "but when you want to do it under conditions where you can manufacture a device where it can be implanted into a body, it will be much more expensive," Cohrs says.

The researchers know they're far from having produced an implantable TAH; this soft heart represents a new concept for future artificial heart development that could one day lead to transplant centers using widely available, easy-to-use design software and commercially available 3D-printers to create a personalized heart for each patient. This kind of artificial heart would be not a bridge to transplantation or, in a few short years, death, but one that would take a person through many years of life.

"My personal goal is to have an artificial heart where you don't have side effects and you don't have any heart problems anymore, so it would last pretty much forever," Cohrs says. Well, perhaps not forever: "An artificial heart valve last 15 years at the moment. Maybe something like that."

9 Fascinating Facts About the Vagus Nerve

The vagus nerve is so named because it “wanders” like a vagabond, sending out sensory fibers from your brainstem to your visceral organs. The vagus nerve, the longest of the cranial nerves, controls your inner nerve center—the parasympathetic nervous system. And it oversees a vast range of crucial functions, communicating motor and sensory impulses to every organ in your body. New research has revealed that it may also be the missing link to treating chronic inflammation, and the beginning of an exciting new field of treatment for serious, incurable diseases. Here are nine facts about this powerful nerve bundle.

1. THE VAGUS NERVE PREVENTS INFLAMMATION.

A certain amount of inflammation after injury or illness is normal. But an overabundance is linked to many diseases and conditions, from sepsis to the autoimmune condition rheumatoid arthritis. The vagus nerve operates a vast network of fibers stationed like spies around all your organs. When it gets a signal for incipient inflammation—the presence of cytokines or a substance called tumor necrosis factor (TNF)—it alerts the brain and draws out anti-inflammatory neurotransmitters that regulate the body’s immune response.

2. IT HELPS YOU MAKE MEMORIES.

A University of Virginia study in rats showed that stimulating their vagus nerves strengthened their memory. The action released the neurotransmitter norepinephrine into the amygdala, which consolidated memories. Related studies were done in humans, suggesting promising treatments for conditions like Alzheimer’s disease.

3. IT HELPS YOU BREATHE.

The neurotransmitter acetylcholine, elicited by the vagus nerve, tells your lungs to breathe. It’s one of the reasons that Botox—often used cosmetically—can be potentially dangerous, because it interrupts your acetylcholine production. You can, however, also stimulate your vagus nerve by doing abdominal breathing or holding your breath for four to eight counts.

4. IT'S INTIMATELY INVOLVED WITH YOUR HEART.

The vagus nerve is responsible for controlling the heart rate via electrical impulses to specialized muscle tissue—the heart’s natural pacemaker—in the right atrium, where acetylcholine release slows the pulse. By measuring the time between your individual heart beats, and then plotting this on a chart over time, doctors can determine your heart rate variability, or HRV. This data can offer clues about the resilience of your heart and vagus nerve.

5. IT INITIATES YOUR BODY'S RELAXATION RESPONSE.

When your ever-vigilant sympathetic nervous system revs up the fight or flight responses—pouring the stress hormone cortisol and adrenaline into your body—the vagus nerve tells your body to chill out by releasing acetylcholine. The vagus nerve’s tendrils extend to many organs, acting like fiber-optic cables that send instructions to release enzymes and proteins like prolactin, vasopressin, and oxytocin, which calm you down. People with a stronger vagus response may be more likely to recover more quickly after stress, injury, or illness.

6. IT TRANSLATES BETWEEN YOUR GUT AND YOUR BRAIN.

Your gut uses the vagus nerve like a walkie-talkie to tell your brain how you’re feeling via electric impulses called “action potentials". Your gut feelings are very real.

7. OVERSTIMULATION OF THE VAGUS NERVE IS THE MOST COMMON CAUSE OF FAINTING.

If you tremble or get queasy at the sight of blood or while getting a flu shot, you’re not weak. You’re experiencing “vagal syncope.” Your body, responding to stress, overstimulates the vagus nerve, causing your blood pressure and heart rate to drop. During extreme syncope, blood flow is restricted to your brain, and you lose consciousness. But most of the time you just have to sit or lie down for the symptoms to subside.

8. ELECTRICAL STIMULATION OF THE VAGUS NERVE REDUCES INFLAMMATION AND MAY INHIBIT IT ALTOGETHER.

Neurosurgeon Kevin Tracey was the first to show that stimulating the vagus nerve can significantly reduce inflammation. Results on rats were so successful, he reproduced the experiment in humans with stunning results. The creation of implants to stimulate the vagus nerve via electronic implants showed a drastic reduction, and even remission, in rheumatoid arthritis—which has no known cure and is often treated with the toxic drugs—hemorrhagic shock, and other equally serious inflammatory syndromes.

9. VAGUS NERVE STIMULATION HAS CREATED A NEW FIELD OF MEDICINE.

Spurred on by the success of vagal nerve stimulation to treat inflammation and epilepsy, a burgeoning field of medical study, known as bioelectronics, may be the future of medicine. Using implants that deliver electric impulses to various body parts, scientists and doctors hope to treat illness with fewer medications and fewer side effects.

The Anti-Spitting Campaigns Designed to Stop the Spread of Tuberculosis

A Dr. Dettweiler sputum flask, circa 1910
A Dr. Dettweiler sputum flask, circa 1910

In the 19th century, cities were grimy places, where thousands of people lived in overcrowded tenement buildings and walked streets polluted with trash, sewage, and the carcasses of dead animals. Unsurprisingly, these cities were also hotbeds of infectious disease.

One of the leading causes of death was tuberculosis, which spreads from person to person in the tiny droplets that spray through the air when an infected person coughs or sneezes. "In the 19th century, tuberculosis [was] the greatest single cause of death among New Yorkers," explains Anne Garner, the curator of rare books and manuscripts at the New York Academy of Medicine Library and the co-curator of the Museum of the City of New York’s new exhibition, "Germ City: Microbes and the Metropolis."

In the 19th century, tuberculosis killed one in every seven people in Europe and the U.S., and it was particularly deadly for city dwellers. Between 1810 and 1815, the disease—then commonly known as consumption, or the white plague—was to blame for more than a quarter of the recorded deaths in New York City. While New York wasn't alone among urban centers in having startlingly high rates of tuberculosis, its quest to eradicate the disease was pioneering: It became the first U.S. city to ban spitting.

"BEWARE THE CARELESS SPITTER"

Anti-tuberculosis pamphlets
Tuberculosis warnings from the Committee on Prevention of Tuberculosis that appeared on New York City streetcar transfers in 1908, reprinted by the Michigan Board of Health in 1909

In 1882, Robert Koch became the first to discover the cause of tuberculosis: a bacterium later named Mycobacterium tuberculosis, which he isolated from samples taken from infected animals. (Koch won the Nobel Prize in 1905 for his work.) He determined that the disease was spread through bacteria-infected sputum, the mix of phlegm and spit coughed up during a respiratory infection. That meant that rampant public spitting—often referred to as expectorating—was spreading the disease.

In 1896, in response to the growing understanding of the threat to public health, New York City became the first American metropolis to ban spitting on sidewalks, the floors in public buildings, and on public transit, giving officials the ability to slap wayward spitters with a fine or a jail sentence. Over the next 15 years, almost 150 other U.S. cities followed suit and banned public spitting [PDF].

The New York City health department and private groups like the National Tuberculosis Association, the Women’s Health Protective Association, and the Brooklyn Anti-Tuberculosis Committee generated anti-spitting slogans such as "Spitting Is Dangerous, Indecent, and Against the Law," "Beware the Careless Spitter," and "No Spit, No Consumption." They made posters decrying spitting (among other unhealthy habits) and reminding people of the ban. Members of the public were encouraged to confront defiant spitters, or, at the very least, give them the stink eye. While there were many other factors to blame for the spread of tuberculosis—like dangerously overcrowded, poorly ventilated tenement housing and widespread malnutrition—public spitters became the literal poster children of infection.

New York City officials followed through on the threat of punitive action for errant spitters. More than 2500 people were arrested under the statute between 1896 and 1910, though most only received a small fine—on average, less than $1 (in 1896, that was the equivalent of about $30 today). Few other cities were as committed to enforcing their sputum-related laws as New York was. In 1910, the National Tuberculosis Association reported that less than half of cities with anti-spitting regulations on the books had actually made any arrests.

Despite the law, the problem remained intractable in New York. Spitting in streetcars posed a particularly widespread, and disgusting, issue: Men would spit straight onto the floor of the enclosed car, where pools of phlegm would gather. Women wearing long dresses were at risk of picking up sputum on their hemlines wherever they went. And the law didn’t seem to stop most spitters. As one disgusted streetcar rider wrote in a letter to the editor of The New York Times in 1903, “That the law is ignored is evident to every passenger upon these public conveyances: that it is maliciously violated would not in some cases be too strong an assertion.”

The situation wasn’t much better two decades later, either. “Expectorating on the sidewalks and in public places is probably the greatest menace to health with which we have to contend,” New York City Mayor John Francis Hylan said in a 1920 appeal for citizens to help clean up the city streets.

THE BLUE HENRY

A blue sputum flask
New York Academy of Medicine Library

Spitting laws weren't the only way that health authorities tried to rein in the spread of TB at the turn of the century. Anti-tuberculosis campaigns of the time also featured their own accessory: the sputum bottle.

Faced with the fact that sick people would cough up sputum no matter what a poster in a streetcar told them, in the late 19th century, doctors and health authorities all over the world began instructing people with tuberculosis to spit into pocket-sized containers, then carry it around with them. “A person with tuberculosis must never spit on the floor or sidewalk or in street cars, but always into a cuspidor or into a paper cup, which he should have with him at all time, and which can be burned,” advised the New York City Department of Health’s 1908 publication Do Not Spit: Tuberculosis (Consumption) Catechism and Primer for School Children. These containers were known as cuspidors, spittoons, or simply sputum cups or sputum bottles.

Among the most well-known of these sputum-carrying receptacles was the “Blue Henry,” a pocket flask made of cobalt-blue glass that was originally manufactured by the German sanatorium pioneer Peter Dettweiler, who himself had suffered from tuberculosis.

“The sputum bottle was like a portable flask that could be used to collect this sticky phlegm that was produced by the irritated lungs of a person suffering from tuberculosis,” Garner says. While they came in various shapes, sizes, and materials, the fancier versions would have a spring-loaded lid and could be opened from both sides, so that you could spit into a funnel-like opening on one side and then unscrew the bottle to clean out the sputum receptacle later.

Dettweiler's device and the similar devices that followed became popular all over the world as doctors and governments sought to contain the spread of tuberculosis. These receptacles became a fixture in hospitals and at sanatoriums where tuberculosis patients went to recuperate, and were a common hand-out from anti-tuberculosis charities that worked with TB-afflicted patients.

In the early 1900s, the New York Charity Organization Society was one of them. Its Committee for the Prevention of Tuberculosis raised money to buy its New York City-based clients better food, new beds, and of course, sputum cups. (Likely the paper kind, rather than the glass Dettweiler flasks.) The generosity wasn't unconditional, though. The society would potentially pull its aid if charity workers showed up for a surprise home inspection to find unsanitary conditions, like overflowing sputum cups that were not being properly disinfected [PDF].

Eventually, the city itself began handing out sputum cups. In an effort to reduce the contagion, by 1916 a large number of cities—such as Los Angeles, Seattle, and Boston—dedicated part of their municipal budgets to paying for tuberculosis supplies like paper sputum cups that would be handed out to the public for free.

A ad for anti-TB supplies from the Journal of Outdoor Life
An advertisement that ran in the Journal of Outdoor Life—which billed itself as “the anti-tuberculosis magazine"—in 1915

Though paper sputum cups could be burned, glass or metal flasks had to be cleaned regularly. Doctors recommended that the sputum bottles contain a strong disinfectant that could kill off the tuberculosis bacilli, and that the receptacles be cleaned and disinfected every morning and evening by rinsing them with a lye solution and boiling them in water. As for the sputum itself, burning was the preferred method of sanitizing anything contaminated with TB at the time, and sputum was no exception—although rural consumptives were encouraged to bury it in the garden if burning wasn’t practical.

In an era where infectious disease was often associated with poor, immigrant communities, sputum bottles made it possible to go out in public without drawing the same attention to your condition that hacking up phlegm into the street would. “You could discreetly carry them around and then take them out and people wouldn’t necessarily know that you were suffering from the disease,” Garner explains. Or at least, somewhat discretely, since they soon became widely associated with consumptives. A Dr. Greeley, for one, argued that ordinary sputum bottles were “so conspicuous as to be objectionable," and suggested people spit into toilet paper and put that in a pouch instead. That idea didn't quite take off.

And while hiding your infectious status is not good for public health, the sputum flasks did lower the risk that you were infecting the people around you as you coughed and sneezed. “As long as you were doing it into the bottle, you probably were not infecting other people,” Garner says.

Not many of these sputum bottles have survived, in part because it was standard practice to burn everything in a tuberculosis patient’s room after they died to prevent germs from spreading. Those that remain are now collector's items, held in the archives of institutes like Australia's Museums Victoria; the Museum of Health Care in Kingston, Canada; and the New York Academy of Medicine Library.

TUBERCULOSIS TODAY

Unfortunately, neither anti-spitting propaganda nor sputum flasks managed to stop the spread of tuberculosis. Real relief from the disease didn’t come until 1943, when biochemist Selman Waksman discovered that streptomycin, isolated from a microbe found in soil, could be an effective antibiotic for tuberculosis. (He won the Nobel Prize for it, 47 years after Koch won his.)

And while carrying a cute flask to spit your disease-ridden phlegm into sounds quaint now, tuberculosis isn’t a relic of the past. Even with medical advances, it has never been eradicated. It remains one of the most devastating infectious agents in the world, and kills more than a million people worldwide every year—the exact number is debated, but could be as high as 1.8 million. And, like many infectious diseases, it is evolving to become antibiotic resistant.

Sputum flasks could come back into fashion yet.

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