Professor and students seek to uncover Nature’s chilling secret
Eric Bredahl, PhD, and his team of undergraduate research assistants are trusting that Nature, if asked nicely, or at least insistently, will yield another of her secrets.
What happens, they want to know, when hibernating animals settle in for their long winter nap? They know hibernators experience a surge of a chemical known as adenosine, that heartbeats subsequently slow dramatically — in the case of a squirrel declining from 300 beats a minute to a few beats per minute, and that the burning of sugars is replaced by the metabolism of lipids.
But how does this extreme state of relaxation last so long without reducing muscle mass or causing heart damage through reduced blood flow, or through the damage that sometimes occurs when normal blood flow resumes?
The answers to these questions carry important implications for the preservation and successful transplantation of a human heart on its speedy journey from donor to recipient. That journey typically takes four to five hours, during which time the heart’s temperature is lowered and metabolism slowed through the use of a chilled organ preservation solution.
Imagine, though, that a hibernation-like process could be used to improve organ storage and double the transport window, thus allowing for a larger donor and recipient pool. The dramatic slowing of function could potentially double its transportation window to 10 or 12 hours, thus allowing residents of difficult-to-reach rural areas better accessibility to donor hearts.
“How do you keep a hibernating animal alive for four months in the absence of food without a reduction in function having any negative effects?” asks Bredahl. “Nature has evolved all these unique mechanisms, unique pathways, and the more we understand about them the more we might be able to take those same mechanisms and apply them to a clinical condition.
“In our case, what we are really interested in is how and why the heart of a hibernator can function at such a low temperature for such an extended period without any ill effects. We have an idea of how that happens. Now we are taking those same processes and applying them to a clinical application like transporting hearts for cardiac transplant.”
Can it be done? Bredahl is hopeful.
“Preliminary data says it may be possible,” he says. “But we are still doing basic research. Every couple of days we add more data and more data. It's very exciting stuff.”
Bredahl, an associate professor in exercise science, is aided in this quest by a $112,000 grant from the Great Plains IDeA Clinical Translational Research Program. The study is formally titled “Expanding the Cardiac Transplant Window: Treatments Derived from Hibernators,” and uses rat hearts to study the response of hearts to hibernation-like influences. It is a joint project of Bredahl and Matt Andrews, PhD, professor in the School of Natural Resources at the University of Nebraska-Lincoln.
And, of course, a group of undergraduates availing themselves of Creighton’s many opportunities for adventures in research.
“This project would not have been possible without our undergrads,” Bredahl says. “Liz Kettler (BS’23) and Nik Johnson (BS’22), for example, put almost a year’s worth of work into this project. It is phenomenal what they did.”
Furthermore, this project received significant help from Frazer Heinis, a post-doctoral researcher at the University of Nebraska-Lincoln.
The incoming cohort of undergraduate students will have similar opportunities, Bredahl said.
“I have about seven of them, and they are going to do a whole variety of things,” he says. “Some of them will work with me on cardiac tissue doing functional assessments. Some of them will do molecular assessment where we try to quantify how much damage is happening from storage, and others will do protein analysis to see if there is any change in regulatory protein expression.
“It will basically be groups of three, and they will have their own research project and every one of them will have something that they can present, hopefully something that they can publish and give them experience that will be second to none.”