Comparative coagulation studies in hibernating and summer-active black bears (Ursus americanus)

Friedrich, Ann-Kristin U.; Kakuturu, Jahnavi; Schnorr, Peter J.; Beyer, Dean E.; Palesty, J. Alexander; Dickson, Eric W.; Basadonna, Giacomo; Cahan, Mitchell A.

doi:10.1016/j.thromres.2017.07.034

Cited by 10 publications

(7 citation statements)

References 7 publications

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“…A steady low level D-dimer level throughout all stages of the annual cycle, along with an inactivated coagulation cascade during hibernation suggested that venous thrombosis is not occurring during hibernation in ground squirrels. This result is consistent with steady low level of Ddimers in active and hibernating black bears (Friedrich et al 2017). However, it is possible that the D-dimers are cleared from circulation before they can be detected.…”

Section: Discussionsupporting

confidence: 87%

“…In contrast to suppression of coagulation, hibernating ground squirrels were in a hyperfibrinolytic state compared to non-hibernators. Plasminogen levels in ground squirrels had a similar fold decrease to that seen in hibernating black bears (1.9 and 1.6 fold respectively) (Friedrich et al 2017). Plasminogen mRNA levels were constant throughout the year, suggesting increased consumption rather than decreased production of plasminogen.…”

Section: Discussionmentioning

confidence: 56%

“…Ground squirrels survive dramatic changes in blood flow during consecutive bouts of torpor and interbout arousals throughout their 6-7-month hibernation season. Ground squirrels, bears, and hamsters have developed antithrombotic adaptations including thrombocytopenia and decreases in vWF, Factor VIII and Factor IX to avoid lethal blood clots during hibernation (Lechler and Penick 1963, Pivorun and Sinnamon 1981, Cooper et al 2012, de Vrij et al 2014, Friedrich et al 2017). However, it is unknown if these adaptations completely block the formation of blood clots.…”

Section: Discussionmentioning

confidence: 99%

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Cardiovascular resistance to thrombosis in 13-lined ground squirrels

et al. 2018

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Thirteen-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 stasisinduced 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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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Cardiovascular resistance to thrombosis in 13-lined ground squirrels

et al. 2018

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“…Low flow is associated with thrombus formation in humans but not in bears. The ability to avoid blood clots seems, at least partly, to be explained by spontaneously reduced platelet aggregation in bears during hibernation but also by downregulation of key coagulation factors . However, levels of the ultimate clotting effector proteins F10 and F2, and those of the fibrinogen substrate subunits FGA and FGG increase in winter in brown bears and indicate some degree of preserved coagulation in order to avoid bleeding.…”

Section: Bear Hibernation Physiologymentioning

confidence: 99%

The brown bear as a translational model for sedentary lifestyle‐related diseases

et al. 2019

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Sedentary lifestyle accelerates biological ageing, is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, kidney failure, sarcopenia and osteoporosis. In contrast to the linear path to worsening health in humans with metabolic syndrome, brown bears have developed a circular metabolic plasticity enabling these animals to tolerate obesity and a ‘sedentary lifestyle’ during hibernation and exit the den metabolically healthy in spring. Bears are close to humans physiology wise, much closer than rodents, the preferred experimental animals in medical research, and may better serve as translational model to develop treatments for lifestyle‐related diseases. In this review, aspects of brown bear hibernation survival strategies are outlined and conceivable experimental strategies to learn from bears are described.

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“…The cardiac adaptations during hibernation are characterized by a profound bradycardia with extreme respiration sinus arrhythmia and a preserved left ventricular ejection fraction, associated with a decrease in left ventricle mass/volume ratio indicating some degree of cardiac remodeling to adapt to the altered hemodynamic state (8)(9)(10). Interestingly, when they emerge from their dens in the spring, bears are free from cardiovascular diseases (11,12), kidney failure (13)(14)(15), sarcopenia (16)(17)(18), osteoporosis (19,20), and other deleterious conditions (21,22). The contrast with physically inactive humans could not be greater (23)(24)(25)(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

Givre

Silva

Swenson

et al. 2021

Front. Cardiovasc. Med.

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Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia–reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 ± 7.06% vs. 79.20 ± 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia–reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.

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Comparative coagulation studies in hibernating and summer-active black bears (Ursus americanus)

Cited by 10 publications

References 7 publications

Cardiovascular resistance to thrombosis in 13-lined ground squirrels

Cardiovascular resistance to thrombosis in 13-lined ground squirrels

The brown bear as a translational model for sedentary lifestyle‐related diseases

Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

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