Metabolic changes in the normal and hypoxic neonatal myocardium.
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.
Abdel-Aleem
S
S
Division of Thoracic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
St Louis
J D
JD
Hughes
G C
GC
Lowe
J E
JE
D000222:Adaptation, Physiological / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012016:Reference Values