This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Ischemia-reperfusion injury (I/R), a mandatory component of cardiac surgery and organ transplantation, remains a major determinant of perioperative morbidity and mortality, escaping multiple protection strategies. Hibernating mammals offer an intriguing example of natural adaptation to physiologic extremes and illustrate the regulatory mechanisms that control metabolic rate depression and the cell preservation strategies that support long-term viability in a hypometabolic state. These suggest applied strategies for improving hypothermic preservation of human organs for transplant, and guidelines that could aid in the development of torpor as a cardio and neuroprotective strategy in the perioperative period. Our proposed model organism is the arctic ground squirrel, an obligate hibernator that enters a supercooled state by lowering core body temperatures to -3-degrees C, followed by return to normothermia without reperfusion injury. Our central hypothesis is that changes in hybernation-specific gene expression and metabolic profiles provide protection against perioperative myocardial and cerebral injury normally associated with I/R.
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