Structural Changes in Heart Disease

During hibernation, a grizzly bear's heart beats at about 18 beats per minute--one fifth the rate it pumps during the rest of the year. A typical human heart beats between 60 and 80 times per minute, and would never get that low, but if it did slow significantly, the atria (upper heart chambers) would distend with the backflow of blood that was not properly circulating....[More]

Structural Changes in Heart Disease

During hibernation, a grizzly bear's heart beats at about 18 beats per minute--one fifth the rate it pumps during the rest of the year. A typical human heart beats between 60 and 80 times per minute, and would never get that low, but if it did slow significantly, the atria (upper heart chambers) would distend with the backflow of blood that was not properly circulating. Such structural changes, collectively termed "cardiac remodeling," happen frequently in the 5 million Americans who have heart failure, often with adverse consequences. Hence, researchers are eager to learn how bears evade remodeling in the hope that it may pave the way for new therapies for humans.

Lynne Nelson, a veterinary cardiologist at Washington State University, took four grizzly bear cubs born in her lab, bottle-fed them, routinely handled them, and acclimated them to a variety of noninvasive tests such as echocardiograms. Now that the bears are grown, she can observe the contractions of their hearts without using anesthesia, which could disrupt normal function. Her research (presented in August at the International Hibernation Symposium in Namibia) suggests that grizzlies' atria cease contracting during hibernation. That may also keep the atria from dilating, she says, because it stops them from having to work against a congested heart.

Nelson also found that during hibernation a protein (N2BA titin) in heart muscle is--in many instances--replaced by N2B, a more rigid form of the same protein. The protein switch may be another strategy bears use to preserve the heart's shape during hibernation.

This hand-reared grizzly is used to having heart ultrasounds (echocardiograms).  [Less] [Link to this slide]

Courtesy Lynne Nelson

Wound Healing and Foreign Body Response

Tim Laske, a biomedical engineer at Medtronic, took a different approach to studying heart function in hibernating black bears. He had his colleagues re-jigger the implantable defibrillators Medtronic makes for humans so that they would record vital functions....[More]

Wound Healing and Foreign Body Response

Tim Laske, a biomedical engineer at Medtronic, took a different approach to studying heart function in hibernating black bears. He had his colleagues re-jigger the implantable defibrillators Medtronic makes for humans so that they would record vital functions. He then implanted these data recorders into several bears. To Laske's surprise, most of the bears mounted such a powerful immune response that they expelled the devices--just as they would a splinter--even when the devices were implanted in the gut The bears, meanwhile, were virtually unscathed. (Imagine a soldier being able to do that with a bullet.)

While they were still functional, the data recorders also led to another important discovery: when bears take a breath, they increase their heart rate by up to 800 percent. Humans also increase their heart rate when they breathe, but only by 20 percent. Laske suspects that the bears' peculiar heart rhythm allows them to rest the heart between breaths and then pump more forcefully when there's a lot of oxygen in the blood. He and collaborator Paul Iaizzo, a heart physiologist at the University of Minnesota, believe that recreating this respiratory sinus arrhythmia in humans with limited heart function could prove therapeutic.

The data recorder [inset] (a little smaller than a pack of cigarettes) worked its way out of a bear's gut and became a chew toy. Researchers use infrared images like this one to measure how much heat a bear emits, and to see how the bear is positioned inside a dark den.  [Less] [Link to this slide]

Courtesy Tim Laske

Preventing Damage from Stroke and Heart Attack

The limited blood flow of hibernation reduces the amount of oxygen that gets to vital organs. Even so, hibernation does not damage the heart or brain. That may be because bears produce a compound called hibernation induction trigger (HIT), which slows cellular metabolism and quells the need for oxygen....[More]

Preventing Damage from Stroke and Heart Attack

The limited blood flow of hibernation reduces the amount of oxygen that gets to vital organs. Even so, hibernation does not damage the heart or brain. That may be because bears produce a compound called hibernation induction trigger (HIT), which slows cellular metabolism and quells the need for oxygen.

Researchers have not identified the active compound in HIT, but they believe it's an endorphin (a chemical that has properties similar to those of morphine), because the effects of HIT are mimicked by drugs that target delta opioid receptors (one of several receptor subtypes that bind to morphine and compounds like it) and are thwarted by drugs that block those receptors.

Another set of opiate-like compounds called deltorphins, derived from the skin of South American frogs, also target delta opioid receptors. So Peter Oeltgen, a biochemist at the University of Kentucky, who has studied HIT for more than 30 years, recently switched to studying deltorphins. According to his research, these compounds help rats survive severe hemorrhage and decrease the damage from strokes induced in mice. He and Iaizzo also found that deltorphins reduced the damage caused by heart attack in pigs. Oeltgen, who co-founded a company called HiberNetics Inc. in Frankfort, Ky., holds patents on deltorphins and believes these compounds will one day be used to treat humans.  [Less] [Link to this slide]

Courtesy Hank Harlow

Preserving Tissues during Surgery or for Transplantation

Surgery often interrupts blood flow to the area being treated, sometimes damaging tissue. During total knee replacement surgery, for example, the muscles surrounding the knee get very little oxygen....[More]

Preserving Tissues during Surgery or for Transplantation

Surgery often interrupts blood flow to the area being treated, sometimes damaging tissue. During total knee replacement surgery, for example, the muscles surrounding the knee get very little oxygen. To recreate this scenario, Iaizzo kept pig muscles alive in a dish but deprived them of oxygen for 90 minutes. Compared with muscles that were pretreated with plasma from non-hibernating woodchucks, muscles that were pre-treated with plasma from hibernating woodchucks showed stronger contractions once oxygen was reinstated. The same is true, he says, when he used plasma from hibernating bears. Oeltgen and others have also used hibernation induction trigger and related compounds to extend the life of donor organs from laboratory animals.

 [Less] [Link to this slide]

Erin Silversmith

Obesity and Diabetes

Polar bears , other than pregnant females, do not hibernate, but they do spend several months fasting in a state of "walking hibernation." As the largest of the bears--living in the harshest climate-- polar bears undergo the most dramatic changes in weight....[More]

Obesity and Diabetes

Polar bears, other than pregnant females, do not hibernate, but they do spend several months fasting in a state of "walking hibernation." As the largest of the bears--living in the harshest climate--polar bears undergo the most dramatic changes in weight. At the beginning of fasting, a male polar bear might weigh 1,300 pounds; at the end, he may weigh only half that much.

Marc Cattet, a wildlife vetrinarian at the University of Saskatchewan in Saskatoon, says that "fat" polar bears (the ones that are ready to fast) do not become diabetic even though they have insulin resistance, a hallmark of diabetes in which cells lose the ability to take up sugar in response to insulin. That's probably because polar bears rarely use sugar as an energy source and instead rely almost entirely on fat--their own or that in their diet, he says.

When humans have to resort to using their own fat stores as an energy source, for example during starvation or uncontrolled diabetes, they can become poisoned with the byproducts of fat breakdown. Bears have found a way around that problem: they simply recycle those byproducts to make more fat. If a hibernation-like state could be recreated in humans, physicians might have an answer to obesity and diabetes. That might not be as far-fetched as it sounds. Monkeys who get injections of a hibernation-induction trigger lose interest in food, Oeltgen found. Plus, there are primates that hibernate in the wild.  [Less] [Link to this slide]

Courtesy U.S. Fish and Wildlife Service

Kidney Disease

Humans with failing kidneys, which cannot excrete the waste normally found in urine, don't survive for long without dialysis (a machine that filters waste from their blood) or a kidney transplant....[More]

Kidney Disease

Humans with failing kidneys, which cannot excrete the waste normally found in urine, don't survive for long without dialysis (a machine that filters waste from their blood) or a kidney transplant. That's because nitrogen, in the form of urea, builds up in the blood and becomes toxic. Bears, on the other hand, go for months without urinating and never develop this problem. They have microbes in their gut that convert urea into a form of nitrogen they can use to make new amino acids--the basic building blocks of protein. In fact, Cattet has shown that polar bears maximize the amount of nitrogen they lock down in protein form by breaking down amino acids that contain just one nitrogen molecule and instead making amino acids that contain multiple nitrogen molecules.

Humans have urea-chomping microbes, too, but we aren't as good as bears at recycling urea. In their book, Sustaining Life: How Human Health Depends on Biodiversity, psychiatrist Eric Chivian and pediatrician Aaron Bernstein, both of Harvard Medical School's Center for Health and the Global Environment, speculate that a better understanding of ursine urea recycling may help not only kidney disease patients, but also malnourished populations in developing countries with limited access to protein foods.

Hank Harlow, who studies urea recycling and muscle physiology in black bears, comes face-to-face with one of his subjects.  [Less] [Link to this slide]

Courtesy Hank Harlow

Muscles--Without the Workout

When Hank Harlow , a physiologist at the University of Wyoming, enters the den of a hibernating black bear, the bear often gets up and runs to the back of the den....[More]

Muscles--Without the Workout

When Hank Harlow, a physiologist at the University of Wyoming, enters the den of a hibernating black bear, the bear often gets up and runs to the back of the den. That's true even if the bear has been lying there for 110 days. A human bedridden for that long could barely stand, let alone run, so Harlow has been hard at work figuring out what keeps bears' muscles strong.

According to Harlow, bears may exercise in a sense, even though they are stationary. Using temperature recorders placed both inside bears and on their collars, Harlow has noticed that bears' skin heats up periodically throughout the day, even when their core temperature remains low. He suspects the heat is a byproduct of shivering or isometric activities that help keep the muscles limber.

Whatever bears do to keep their muscle strength, the U.S. space agency NASA wants scientists to figure it out. The agency helps fund Harlow and other bear researchers, in hopes of finding solutions to the muscle weakening and bone loss that often accompany space travel.

Using a device similar to one used in humans, Harlow has shown that black bears lose just 29 percent of their muscle strength after 110 days of hibernation.  [Less] [Link to this slide]

Courtesy Paul Iaizzo

Osteoporosis

People who are bedridden become vulnerable to bone breaks and fractures because bones weaken with inactivity. Seth Donahue , a biomedical engineer at Michigan Technological University in Houghton, Mich., found that the bones of hibernating bears escape that fate, possibly because bears make a particularly potent form of a hormone secreted by the parathyroid glands (small endocrine glands in the neck)....[More]

Osteoporosis

People who are bedridden become vulnerable to bone breaks and fractures because bones weaken with inactivity. Seth Donahue, a biomedical engineer at Michigan Technological University in Houghton, Mich., found that the bones of hibernating bears escape that fate, possibly because bears make a particularly potent form of a hormone secreted by the parathyroid glands (small endocrine glands in the neck). The hormone stimulates the formation of new bone, and a synthetic version called Forteo is already used to treat osteoporosis in humans. Still, drug developers at the biotech company Aursos (from the Latin for bear) believe that ursine parathyroid hormone will outdo its human counterpart, noting that bears do not suffer from the bone-thinning disorder and, also, the bear version was more effective at preventing death in bone-forming cells in lab cultures.

This bear femur is being tested for strength. Compared with femurs from non-hibernating grizzlies, femurs from hibernating grizzlies take the same "energy to failure," meaning they break with the same force.  [Less] [Link to this slide]

Courtesy Seth Donahue

Planned Pregnancy

Bears give a whole new meaning to the term "planned pregnancy." Eggs fertilized during the mating season do not implant or begin developing until weeks or months later when the female is ready to den....[More]

Planned Pregnancy

Bears give a whole new meaning to the term "planned pregnancy." Eggs fertilized during the mating season do not implant or begin developing until weeks or months later when the female is ready to den. Scientists used to believe this embryonic diapause gave the female room to decide whether to invest in a pregnancy, depending on whether she had enough fat stores to sustain the young. Michael Vaughan, a wildlife biologist at Virginia Tech, found, however, in work yet to be published, that’s not the case. In his lab, black bears that don't get enough food to gain the weight they typically need to prep for denning still proceed with pregnancy and give birth normally. However, the cubs die, presumably because the mother bear cannot produce milk. Bears given ample food reproduce normally. These findings don't bring biologists any closer to understanding the trigger for implantation, but they do lay to rest some ideas about why diapause occurs. Studies in humans, meanwhile, indicate that women can apparently hit the pause button on pregnancy, too, but no one knows how. For example, in one study, a woman who had received in vitro fertilization had a normal pregnancy, but the fetus's development was delayed by 5 weeks, presumably because its implantation was stalled.

This cub was born in the Vaughan lab.  [Less] [Link to this slide]

Courtesy Mike Vaughan

Cute as Teddy Bears When Laske, Iazzo, and Harlow (all collaborators) return to the den of the female bears they study in late winter, they often find new cubs. [Link to this slide]
Courtesy Tim Laske

Gall Stones and Liver Disease

Ursodiol (ursodeoxycholic acid), a compound originally derived from bear bile (a substance secreted by the liver that helps break down fat), is already used in Western medicine to dissolve cholesterol-laden gall stones and to treat a form of liver disease called primary biliary cirrhosis ....[More]

Gall Stones and Liver Disease

Ursodiol (ursodeoxycholic acid), a compound originally derived from bear bile (a substance secreted by the liver that helps break down fat), is already used in Western medicine to dissolve cholesterol-laden gall stones and to treat a form of liver disease called primary biliary cirrhosis. Despite the availability of a synthetic version of the compound, as many as 13,000 bears are still kept captive on farms in China, Vietnam and other parts of Asia, where they are milked for their bile. David Garshelis, co-chair of the Bear Specialist Group for the International Union for Conservation of Nature, was allowed to visit one of these bile farms, probably because its practices are among the most humane. While the bears he saw were in good conditions, he says the bear rescue organization Animals Asia routinely takes in bile bears that show evidence of torture. While these practices may seem jarring, keep in mind that in the U.S. and Canada, 50,000 black bears are killed annually for food and another 2,000 brown bears are killed for sport.

According to traditional Chinese medicine, the benefits of bile extend beyond those of ursodeoxycholic acid. Intriguingly, when Oeltgen injected rabbits with radioactively labeled opiate-like compounds similar to the ones thought to be found in hibernation induction trigger, he found that they were excreted through the bile.

These Asiatic black bears enter their stalls when called to be milked for bile.  [Less] [Link to this slide]

Courtesy David Garshelis