Abdel-Aleem S, St Louis J D, Hughes G C, Lowe J E
Division of Thoracic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ann N Y Acad Sci. 1999 Jun 30;874:254-61. doi: 10.1111/j.1749-6632.1999.tb09240.x.
Hypoxia is characterized by inadequate oxygen delivery to the myocardium with a resulting imbalance between oxygen demand and energy supply. Several adaptive mechanisms occur to preserve myocardial survival during hypoxia. These include both short- and long-term mechanisms, which serve to achieve a new balance between myocardial oxygen demand and energy production. Short-term adaptation includes downregulation of myocardial function along with upregulation of energy production via anaerobic glycolysis following an increase in glucose uptake and glycogen breakdown. Long-term adaptation includes genetic reprogramming of key glycolytic enzymes. Thus, the initial decline in high-energy phosphates following hypoxia is accompanied by a decrease in myocardial contractility and myocardial energy requirements are subsequently met by ATP supplied from anaerobic glycolysis. Thus, a downregulation in cardiac function and/or enhanced energy production via anaerobic glycolysis are the major mechanisms promoting myocardial survival during hypoxia. In contrast to the aforementioned metabolic changes occurring in adult myocardium, the effects of chronic hypoxia on neonatal myocardial metabolism remain undefined. Studies from our laboratory using a novel neonatal piglet model of chronic hypoxia have shown a shift in cardiac myocyte substrate utilization towards the newborn state with a preference for glucose utilization. We have also shown, using this same model, that chronically hypoxic neonatal hearts were more tolerant to ischemia than non-hypoxic hearts. This ischemic tolerance is likely due to adaptive metabolic changes in the chronically hypoxic hearts, such as increased anaerobic glycolysis and glycogen breakdown.
缺氧的特征是心肌的氧气供应不足，导致氧气需求与能量供应之间失衡。在缺氧期间会出现几种适应性机制来维持心肌存活。这些机制包括短期和长期机制，其作用是在心肌氧气需求和能量产生之间实现新的平衡。短期适应包括心肌功能下调，以及在葡萄糖摄取和糖原分解增加后通过无氧糖酵解上调能量产生。长期适应包括关键糖酵解酶的基因重编程。因此，缺氧后高能磷酸盐的最初下降伴随着心肌收缩力的降低，随后无氧糖酵解提供的ATP满足了心肌的能量需求。因此，心脏功能下调和/或通过无氧糖酵解增强能量产生是缺氧期间促进心肌存活的主要机制。与成年心肌中发生的上述代谢变化相反，慢性缺氧对新生心肌代谢的影响仍不明确。我们实验室使用一种新型慢性缺氧新生仔猪模型进行的研究表明，心肌细胞底物利用向新生儿状态转变，偏好葡萄糖利用。我们还使用同一模型表明，慢性缺氧的新生心脏比非缺氧心脏对缺血更具耐受性。这种缺血耐受性可能是由于慢性缺氧心脏中的适应性代谢变化，如无氧糖酵解和糖原分解增加。
