This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease is the leading cause of death in Americans. Even with successful resuscitation, long-term survivorship following cardiac arrest is poor. To date, no definitive treatment for the ischemia associated with stroke or cardiac arrest is available. The purpose of this study is to demonstrate the utility of a novel model for ischemia tolerance- the mammalian hibernator. Each winter season, hibernators likely experience approximately 15 natural periods of ischemia as they enter each torpor cycle. Research indicates that hibernators are inherently more tolerant to ischemia than are rats. The comparison of mechanisms employed by hibernators to resist the effects of ischemia with mechanisms implicated in ischemic injury incurred in rats may allow for the future development of targeted therapies to promote survivorship in humans. In this study, we will better define the onset, extent and duration of the ischemic insult in the context of the natural rhythms of the hibernator as well as develop a manipulatable model for the induction of ischemia that allows for direct comparison of responses in the ground squirrel to those of the rat. Ultimately, this model will be utilized in the development of an NIH RO1-sustainable program to identify the mechanisms of ischemia tolerance for later application in human medicine.
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