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Myocardial ischemic protection in natural mammalian hibernation

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Abstract

Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

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Acknowledgments

This study was supported by funding from National Institutes of Health (5R01HL091781, 5R21HL97264, 5R01HL093481, 1R01HL106511, 5P01AG027211, 1R01HL102472, 5R01HL033107, 5T32HL069752, 5R01HL095888, 5P01HL069020).

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    Authors and Affiliations

    1. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers-New Jersey Medical School, 185 South Orange Ave, MSB G-609, Newark, NJ, 07103, USA

      Lin Yan, Raymond K. Kudej, Dorothy E. Vatner & Stephen F. Vatner

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    1. Lin Yan
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    2. Raymond K. Kudej
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    3. Dorothy E. Vatner
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    Correspondence to Stephen F. Vatner.

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    L. Yan and R. K. Kudej contributed equally to this work.

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    Yan, L., Kudej, R.K., Vatner, D.E. et al. Myocardial ischemic protection in natural mammalian hibernation. Basic Res Cardiol 110, 9 (2015). https://doi.org/10.1007/s00395-015-0462-0

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