February 19, 2013 in Health

The hearts of bears and men

WSU researchers find clues in grizzlies’ tickers that could help fight cardiovascular disease
By The Spokesman-Review
 
Tyler Tjomsland photoBuy this photo

Above: A pair of bear cubs are seen playing at WSU’s Bear Center through a live-feed camera to associate cardiology professor Dr. Lynne Nelson’s computer. At right: Nelson poses outside her Pullman office.
(Full-size photo)

How do you perform an echocardiogram on a grizzly bear? Very carefully.

But, if you want reliable results, you don’t drug the bears – the researchers at Washington State University’s Bear Center learned that anesthesia affects how grizzlies’ hearts perform, muddling their findings. That’s why scientists there trained four grizzlies from early cubhood to participate in testing: They come when they’re called, amble into large crates, crouch into position – elbows up on a log – and let the researchers pass over their chests with an ultrasound device, creating detailed images of their beating hearts.

Now a decade on the job, the trained grizzlies have contributed to a body of research that scientists hope will help humans combat heart disease, the leading cause of death for men and women in the United States. Noting that the bears remain mostly inactive during winter hibernation but emerge in the spring with healthy hearts, the researchers are studying the differences between grizzly and human hearts and the reasons behind them.

“They do a lot of things that either we do and are quite dangerous when we do them, or we can’t do that would be quite helpful for us to do,” said Dr. Charles Robbins, the center’s director.

Among their most notable findings: During hibernation, bears shut down two of their hearts’ four chambers, which conserves energy while they’re not eating or drinking – but also helps preserve their hearts, said Dr. Lynne Nelson, assistant director of the Bear Center.

They’ve also found that while muscle mass in one chamber shrinks during hibernation, the chamber doesn’t dilate, or balloon. In a person with such a low heart rate, on the other hand, the chamber would dilate. And a dilated chamber in a person – normally caused by coronary artery disease, thyroid disease, diabetes, viral infections or other problems – would affect the heart’s ability to pump blood.

Looking to explain the grizzlies’ healthy hearts, the researchers found that grizzlies “upregulate” a muscle protein in their heart, called titin, that stiffens the chamber, so it can still do its job during hibernation. When a human’s ventricular chamber gets sick, it gets less of that protein, becoming more flexible – and less able to do its job.

Drug and biotechnology companies have shown interest in the findings, Nelson said, as potential ammunition against heart disease. By learning how the grizzlies’ bodies know to add muscle protein, scientists could mimic that process in humans through medication or genetic engineering.

“We’re big mammals, too,” Nelson said. “There are primates that hibernate, and having some of this genetic material in us, too, is possible. We could have the physiology it takes to accomplish this.”

In another project, yet to be published, graduate student Danielle Rivet is studying how different kinds of fat affect the bears’ heart function and hibernation patterns. Two bears get diets high in unsaturated fat, such as salmon, salmon oil, oats and apples. The other two get lots of red meat, high-fructose corn syrup, cheddar cheese and pastries.

Until she started working at the center in May, Rivet’s research had focused on smaller animals – birds and small lizards in Australia, river otters in New York.

“I’ve never really gotten to do much with large animals,” she said. “It’s definitely a new experience.”

Opened in 1986, the Bear Center is the only facility in the world to house grizzlies for research. Its 12 bears, ages 2 to 16 and weighing up to 750 pounds, are used in a variety of other medical research projects. Among them, researchers are trying to figure out why hibernating bears don’t lose bone density or muscle strength during hibernation and how they manage to become “essentially diabetics during the winter” but recover in the spring, Robbins said.

The work with the trained grizzlies started a decade ago.

Nelson, an associate professor of cardiology and a veterinarian, wanted to know how the grizzlies’ hearts looked and functioned during hibernation – and why they didn’t suffer congestive heart failure or other problems that a person would experience, and likely die of, at very low heart rates.

Researchers already knew grizzlies’ hearts slow during hibernation, documented as low as four beats a minute and averaging around 16, compared with 84 beats a minute when they’re not hibernating.

They also knew bears’ hibernation is different from the deep hibernation seen in rodents.

“Bears are more like they’re sleeping,” Nelson said. “They can easily wake up, they can walk around, they can walk outside and sit in the sun, which they commonly do here in our mild winters. And they still have these very, very low heart rates, but they’re very functional.”

Bear Center researchers initially studied the hearts of the center’s other bears – orphaned cubs or wild bears who’d had too many encounters with humans, for example. But to do so, they had to sedate them, which interfered with the grizzlies’ heart rates and other functions. They decided to train the four grizzlies to undergo heart readings, blood-pressure readings and blood draws, receive injections, allow people to place collars on them and take samples of their hair – without anesthesia.

The researchers raised the cubs two at a time. The older pair are 10 now, and the younger two are 8.

Raising and training the cubs, Robbins said, “was one of the top five highlights of probably all of our professional careers.”

Four people shared cub duties, taking the grizzlies from their mothers three days before their eyes opened, at about 6 weeks old.

“They’re like a human baby, I imagine,” Robbins said. “They need feeding every couple of hours through the night. They would start screaming at 2 a.m., and you couldn’t get them far enough away from you in your house. … After a couple of days, you’d get punch-drunk and pass them off.”

Tempted to tuck them into their own beds at night, the researchers found that the grizzly cubs were kickers, constantly in motion and impossible to sleep with, Robbins said. The cubs slept in padded warm boxes, carried back and forth between their homes and offices.

After about two months, the researchers transferred the cubs back to the Bear Center, continuing to bottle-feed them. If they weren’t sucking on a bottle, they’d want to suck on something else. The researchers provided human pacifiers.

“We made two rules early on,” Robbins said. “One was that we would never play with them, we would never wrestle with them. And the other was that we would never let our hands go into their mouths.”

They have photos of the bears, at 3 or 4 years old and 300 pounds, sucking on pacifiers and sitting between the researchers’ legs.

To train the bears, the researchers used a combination of “clicker training,” a positive-reinforcement method often used for training dogs, and honey rewards.

The four bears know their names – Mica, Luna, Peeka and Kio – and come when they’re called. It’s easy to think of them as almost-domestic animals, Nelson said.

But they’re still grizzlies. In 2010, two of the trained bears used in heart research killed a younger bear.

Because the captive bears are well-fed, they don’t compete for food. But older adults and young cubs rarely mix well if they’re not related, Nelson said. That was the problem in the 2010 incident, she said.

“It was just an unfortunate mix of ages of animals that probably shouldn’t have happened,” she said. “It was the first introduction of the grouping, and unfortunately they seemed to get along initially OK, and then didn’t.”

The center is housed in a 1960s building originally designed for primates and adapted for the bears. In a proposal for a new, $12 million facility, the two-acre enclosure would grow to 20 acres, among other improvements.

Nelson said she’s hoping the university’s administrators make it a priority. In the meantime, after a decade spent observing the hearts of bears, she has work to do: “I know more questions now than I know answers.”


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