Yan Lin, Kudej Raymond K, Vatner Dorothy E, Vatner Stephen F
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.
Basic Res Cardiol. 2015 Mar;110(2):9. doi: 10.1007/s00395-015-0462-0. Epub 2015 Jan 23.
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.
冬眠心肌是一种因慢性心肌缺血而保护心脏的重要临床综合征，因其被认为类似于冬季冬眠的哺乳动物而得名。然而，心肌缺血保护作用从未在真正的哺乳动物冬眠中进行过研究，而冬眠是一种在极端冬季环境压力下生存的独特策略。本研究的目的是验证这样一个假设：在土拨鼠冬季冬眠时，缺血应激也可能得到保护。通过冠状动脉闭塞后再灌注，在冬季自然冬眠和未冬眠的土拨鼠以及夏季不冬眠的土拨鼠中诱导心肌梗死。各实验组之间的危险缺血面积相似。与夏季相比，无论是否冬眠，冬季土拨鼠的心肌梗死明显较少，且与缺血预处理后的情况相似。在冬眠的土拨鼠和进行缺血预处理时，均有几种基因上调或下调，但有一种机制是冬眠所特有的，即激活环磷酸腺苷反应元件结合蛋白（CREB）。当CREB在夏季上调时，它诱导的保护作用与冬季土拨鼠心脏中观察到的相似。冬眠时的心脏保护作用也是由内皮型一氧化氮合酶介导的，而不是诱导型一氧化氮合酶。因此，冬眠的土拨鼠心脏是研究心脏保护作用的一种新模型，主要有两个原因：（1）在没有任何预处理刺激的情况下，冬季自然会出现强大的心脏保护作用；（2）它类似于缺血预处理，但具有新的机制，使得这个模型可能对临床转化有用。
