Revealing nature's solution to reperfusion injury using hibernating ground squirrel

Ischemic reperfusion injury (IRI) refers to cellular damages that occur from restoration of blood flow following an ischemic event. The abrupt return of blood flow paradoxically trigger oxidative stress, inflammation, and cellular dysfunction. Despite substantial advances in our understanding of its mechanisms and development of therapeutic strategies, IRI remains a major clinical challenge highlighting the need for new biological insights. Hibernators are a natural model of IRI. In seasonal hibernators, animals experience periods of torpor, a state of energy conservation where animals maintain a persistently lower body temperature and metabolic rate. Torpor is interrupted periodically by interbout arousals (IBA), where the animals will regain euthermic body temperature and other active physiological variables such as blood pressure, blood flow, and heart rate for a short period of time. During hibernation, animals experience repeated IBAs simulating repeated exposure to ischemia and reperfusion. This cycle of ischemia and reperfusion imposes significant ischemic-reperfusion stress. However, previous research has shown that hibernating ground squirrels appear to be resistant to IRI. The goal of this study is to assess whether the 13-lined ground squirrels displayed changes in vascular reactivity after an ischemic event that may contribute to protection against IRI. We hypothesize that 13-lined ground squirrels are naturally protected against IRI do so, in part, by increasing vasoreactivity to accommodate changes is blood flow to withstand repeated ischemic events and this effect is more pronounced during IBA. IRI was artificially induced in 13-lined ground squirrels by performing transient unilateral common carotid artery occlusion (3 cycles of 10 minutes occlusion and 10 minutes reperfusion). Isometric contraction/relaxation was measured in isolated common carotid arteries ex vivo using wire myography. Our preliminary data in summer active squirrels showed that maximum vasoconstriction by phenylephrine (PE; 10-5 M) was increased in arteries that were exposed ischemia-reperfusion compared to the controls. Increased in vasoconstriction suggests that the summer active squirrels are not protected against endothelial dysfunction from IR. Thus, the protection against IRI appear to be state-dependent, specifically during torpor or IBA rather than an inherent species characteristic. Previous research has shown that IBA is associated with decreased vascular oxidative stress and inflammation, which may contribute to resistance to IRI. However, it is yet known whether these mechanisms lead to changes in vasoreactivity. Studies are now underway to investigate whether the torpor or IBA state play a role in IRI resistance. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.