Hibernators may hold the key for better human organ preservation
San Diego, CA -- When most of us think of hibernating animals, we think of bears. But a more commonly sighted hibernator, with a more remarkable story, is the 13-lined ground squirrel. These small mammals, often erroneously called "gophers," are actually relatives of chipmunks and ground hogs and are commonly seen around the golf courses, lawns and prairies of the American Midwest. Although a problem for groundskeepers because of their habit of digging holes, soon they could be famous for providing clues to keeping life-saving human transplant organs viable for extended periods of time.
Like bears, hibernating ground squirrels annually undergo a dramatic shift in their physiology. This state, called "torpor," allows hibernators to use minimum amounts of energy to sustain themselves by using stored body fat throughout the winter. The condition is further characterized by, a heartbeat slowed to just a few beats per minute, going long periods without taking a breadth, and reduced blood flow to the regions of the body.
What makes the hibernating ground squirrels unique among all hibernators is that they are able to bring their body temperature to near-zero degrees Celsius, or just a few degrees above their surrounding air temperature. (Their Alaska kin, for example, are able to reduce their body temperature to minus two degrees Celsius.) This stands in stark contrast to the body changes in bears, which drop their body temperature to only a few degrees below their normal body temperature. Among we non-hibernating humans such a precipitous drop would prove fatal.
How is that these animals can go into such extreme states of cold and, more importantly, come out of them without any apparent damage? What, if anything, can we learn from the "cold storage" process of this unique member of the animal kingdom?
Understanding the means by which these fist size animals can withstand such dramatic changes is the passion and work of Hannah V. Carey, Professor, Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI. Dr. Carey will discuss her latest findings during the upcoming scientific meeting, "The Power of Comparative Physiology: Evolution, Integration and Application," a program of the American Physiological Society (APS), being held August 24-28, 2002 at the Town & Country Hotel, San Diego, CA. To learn more about the conference and presentations, go to: http://www.the-aps.org/meetings/aps/san_diego/home.htm
Thus far, she and her colleagues have hibernating ground squirrels do experience physiological changes that are stressful for the body. They have also uncovered some of the defense mechanisms the squirrels have to cope with the stress that occurs during hibernation. Her current research is designed to apply these principles to organ preservation.
A hibernating animal's intestines display evidence of oxidative stress during the hibernation season. Oxidative stress occurs when reactions lead to an increase in the production of molecules called free radicals, which have the potential to damage other cellular molecules, such as proteins, lipids and DNA. Oxidative stress is common if blood flow to a certain tissue is interrupted and then later resumes. This change in oxygen delivery can lead to a burst of free radicals.
One of the most important antioxidants is glutathione, a molecule that helps by acting as an antioxidant through scavenging and detoxifying free radicals. Changes in the glutathione system occur in the intestine, indicating the system is under stress during the hibernation season.
At the same time, the intestine shrinks as a response to the lack of food during the hibernation season. Except for the shrinkage, there is no evidence that gut (small and large intestines) is damaged during hibernation, yet there are indications that stress has occurred. Carey postulates that cellular pathways are being activated to combat the stress, and does so through the production of defensive molecules. These molecules appear to help protect the hibernator from any damage that could occur. Carey says that it is likely that the intestinal cells are responding to stress and may be generating specific proteins in an attempt to minimize damage.
Do these finding shed any light on what we know of human physiology? Yes, according to Carey.
A Case In Point: Human Liver Transplantation
Consider the case of a patient with a serious illness who needs a liver transplant in order to survive. Once a donor is identified, the donor liver is harvested and then must be transported to the patient's hospital. As the minutes tick by the viability of the donor liver becomes jeopardized. Thus, cold storage is used to keep organs like the liver in a "stasis" condition to preserve their viability. Currently, donor livers only remain viable if their cold storage time does not exceed 24 hours.
Cold storage banking of the liver of a torpid hibernating ground squirrel has shown that the viability of the liver is significantly longer before it shows signs of damage when compared to the liver of a non-hibernating animal, such as a rat or even the liver of a ground squirrel during summer. The physiology of these small creatures may hold the key to improvements in organ preservation and transplantation.
Hibernating ground squirrels switch their physiology so that their organs, such as the gut and liver, can tolerate cold storage during the winter. These researchers are trying to understand the mechanisms of this remarkable ability at the cellular and molecular level and translate the findings into broader-based application for humans.
The American Physiological Society (APS) is one of the world's most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions by which animals live, and ultimately underlie human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.
NEWSROOM OPENS SATURDAY AUGUST 24, 2002 @ 12:00 NOON PST
APS Newsroom: August 24-29, 2002 Town & Country Hotel, San Diego, CA Tel: 619.908.5069 Or: 619.291.7131 ext. 3941