VANCOUVER, B.C.—The 13-lined hibernating ground squirrel may provide clues to keeping organs cold and well preserved for prolonged periods, according to research presented at the 2011 World Congress of Nephrology.
Alkesh Jani, MD, Associate Professor of Nephrology at the University of Colorado in Denver, described research aimed at understanding the molecular underpinnings of how the squirrels lower their body temperatures to 4oC (39.2o F) during the winter without causing any organ damage.
Medical research has not yet created the perfect conditions for preserving organs from deceased or living donors outside of the body for more than 36 hours, Dr. Jani said. Both preservation solutions and machine perfusion have their drawbacks, and the jury is still out regarding their long-term benefits, he said.
“There have been a number of studies published in the last five years looking at pharmacologic and gene therapy approaches targeting injurious molecules that are generated during organ preservation or reperfusion when the donor organ is implanted,” he observed. “Each of these has a beneficial effect on ischemia-reperfusion injury.”
He presented results of some of the work he and his colleagues performed on a colony of hibernating ground squirrels housed at the university. The studies reveal that during the winter these animals’ core body temperature falls to 4oC for up to two weeks at a time, with a concomitant significant decrease in heart and respiratory rates. There is a cyclical alternation between two weeks of cold-temperature torpor and 12 hours of normal physiological temperature of 36oC (96.8o F) and normal physiological function including organ perfusion.
During the cold period, the squirrels’ serum creatinine rises significantly with no concomitant significant increase in the activity of caspase-3—a key enzyme involved in kidney-cell death—and no apoptosis or necrosis.
“So then we looked at what happened to renal function when they rewarmed during their periodic return to normal physiologic temperature and function, and, amazingly, their serum creatinine returned to normal and their urine osmolality increased,” Dr. Jani said. “There also was a significant but small increase in caspase-3 activity but, importantly, this did not translate into significantly increased tubular cell death by apoptosis. The animals were entirely normal.”
He and his co-investigators are continuing to probe these phenomena to determine whether they can be replicated through artificial means in human organs.
Jagbur Gill, MD, MPH, Assistant Professor of Nephrology at the University of British Columbia in Vancouver and a co-chair of the session in which Dr. Jani presented the data, said this approach is “quite novel.”
“What they’ve done is determined that the hibernating ground squirrel is an effective model for organ preservation,” Dr. Gill told Renal & Urology News. “It’s certainly got potential. Because one of the major limitations is reperfusion injury, so this may help us make that next jump forward.”