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Cardiovascular resistance to thrombosis in 13-lined ground squirrels

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Abstract

13-lined ground squirrels (Ictidomys tridecemlineatus) enter hibernation as a survival strategy during extreme environmental conditions. Typical ground squirrel hibernation is characterized by prolonged periods of torpor with significantly reduced heart rate, blood pressure, and blood flow, interrupted every few weeks by brief interbout arousals (IBA) during which blood flow fluctuates dramatically. These physiological conditions should increase the risk of stasis-induced blood clots and myocardial ischemia. However, ground squirrels have adapted to survive repeated bouts of torpor and IBA without forming lethal blood clots or sustaining lethal ischemic myocardial damage. The purpose of this study was to determine if ground squirrels are resistant to thrombosis and myocardial ischemia during hibernation. Blood markers of coagulation, fibrinolysis, thrombosis, and ischemia, as well as histological markers of myocardial ischemia were measured throughout the annual hibernation cycle. Hibernating ground squirrels were also treated with isoprenaline to induce myocardial ischemia. Thrombin–antithrombin complex levels were significantly reduced (p < 0.05) during hibernation, while D-dimer level remained unchanged throughout the annual cycle, both consistent with an antithrombotic state. During torpor, the ground squirrels were in a hyperfibrinolytic state with an elevated ratio of tissue plasminogen activator complexed with plasminogen activator inhibitor to total plasminogen activator inhibitor (p < 0.05). Histological markers of myocardial ischemia were reversibly elevated during hibernation with no increase in markers of myocardial cell death in the blood. These data suggest that ground squirrels do not form major blood clots during hibernation through suppression of coagulation and a hyperfibrinolytic state. These animals also demonstrate myocardial resistance to ischemia.

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Acknowledgements

We would like to thank Amy Cooper, for her care of the ground squirrels and surgical expertise. This work was supported by grants from the NIH (1R15HL093680) to SC.

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  1. Biology Department, University of Wisconsin-La Crosse, 1725 State St. La Crosse, La Crosse, WI, 54601, USA

    Alison Bonis, Leah Anderson, Gaëlle Talhouarne, Emily Schueller, Jenna Unke, Catherine Krus, Jordan Stokka, Anna Koepke, Brittany Lehrer, Anthony Schuh & Scott Cooper

  2. Gundersen Health System, La Crosse, WI, 54601, USA

    Jeremiah J. Andersen

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  1. Alison Bonis
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  2. Leah Anderson
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Contributions

SC, AB and LA conceived the ideas and designed the experiments. GT and BL performed the fibrinolysis assays. LA, AB, KC, JU, JJA, and ES performed the myocardial infarction experiments. AB, JS, AS and AK assayed markers of coagulation and fibrinolysis.

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Correspondence to Scott Cooper.

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No conflicts of interest, financial or otherwise, are declared by the author(s).

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Communicated by H. V. Carey.

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Bonis, A., Anderson, L., Talhouarne, G. et al. Cardiovascular resistance to thrombosis in 13-lined ground squirrels. J Comp Physiol B 189, 167–177 (2019). https://doi.org/10.1007/s00360-018-1186-x

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