glycogen and Fetal-Hypoxia

It has been known for may years that hypoxaemia in the fetus induces a number of biophysical, cardiovascular, endocrine and metabolic responses by the fetus, some of which are not sustained if the period of hypoxaemia is extended. For instance, fetal breathing and body movements and the circulating concentrations of many of the stress-related hormones return to control levels during prolonged periods of hypoxaemia. In particular, circulating fetal blood glucose concentrations gradually return to control levels, after an initial increase. The initial increase is primarily due to a catecholamine-mediated increase in glucose production from glycogen stores leading to a marked reduction in glycogen content. During prolonged periods of hypoxaemia, however, the decrease in fetal blood glucose concentrations is principally due to a decrease in the activity of the major enzymes responsible for glycogenolysis and not to a total depletion of glycogen stores. It is suggested that the decrease in enzyme activity could be due to a prostaglandin E2-mediated antagonism of catecholamine-activated glycogenolysis. In contrast, fetal blood lactate concentrations increase to a plateau after 4-5 h of hypoxaemia and remain at this elevated level for the duration of the hypoxaemia. Circulating lactate concentrations do not increase further, despite production by hypoxic tissues remaining high, due to an increase in lactate clearance by the placenta; under normal conditions the placenta releases lactate into the fetal circulation. It is considered that many of these changes are important adaptive responses which allow the fetus to survive in a sub-optimal intrauterine environment.

Topics: Dinoprostone; Fetal Blood; Fetal Hypoxia; Fetus; Glucose; Glycogen; Humans

Topics: Animals; Blood Glucose; Combined Modality Therapy; Female; Fetal Blood; Fetal Hypoxia; Fetal Movement; Glucose; Glycogen; Glycolysis; Humans; Insulin; Nikethamide; Obstetric Labor Complications; Obstetric Labor, Premature; Oxygen Inhalation Therapy; Placenta; Pregnancy; Respiration; Sheep

Topics: Amino Acids; Animals; Brain; Electrolytes; Endocrine System Diseases; Enzymes; Female; Fetal Diseases; Fetal Hypoxia; Fetus; Glucose; Glycogen; Humans; Ketone Bodies; Lipid Metabolism; Nutrition Disorders; Oxygen; Pregnancy

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Chronic Disease; Disease Models, Animal; Epinephrine; Fatty Acids, Nonesterified; Female; Fetal Heart; Fetal Hypoxia; Glucagon; Glycogen; Heart Rate; Lactates; Norepinephrine; Pregnancy; Propranolol; Regional Blood Flow; Sheep; Vasopressins

The developmental program of the heart requires accurate regulation to ensure continuous circulation and simultaneous cardiac morphogenesis, because any functional abnormalities may progress to congenital heart malformation. Notably, energy metabolism in fetal ventricular cells is regulated in a manner that differs from adult ventricular cells: fetal cardiomyocytes generally have immature mitochondria and fetal ventricular cells show greater dependence on glycolytic ATP production. However, although various characteristics of energy metabolism in fetal ventricular cells have been reported, to our knowledge, a quantitative description of the contributions of these factors to fetal ventricular cell functions has not yet been established. Here, we constructed a mathematical model to integrate various characteristics of fetal ventricular cells and predicted the contribution of each characteristic to the maintenance of intracellular ATP concentration and sarcomere contraction under anoxic conditions. Our simulation results demonstrated that higher glycogen content, higher hexokinase activity, and lower creatine concentration helped prolong the time for which ventricular cell contraction was maintained under anoxic conditions. The integrated model also enabled us to quantitatively assess the contributions of factors related to energy metabolism in ventricular cells. Because fetal cardiomyocytes exhibit similar energy metabolic profiles to stem cell-derived cardiomyocytes and those in the failing heart, an improved understanding of these fetal ventricular cells will contribute to a better comprehension of the processes in stem cell-derived cardiomyocytes or under pathological conditions.

Topics: Action Potentials; Adenosine Triphosphate; Animals; Computer Simulation; Energy Metabolism; Fetal Heart; Fetal Hypoxia; Glycogen; Glycolysis; Guinea Pigs; Heart Ventricles; Hexokinase; Models, Cardiovascular; Myocytes, Cardiac; Oxidative Phosphorylation; Sarcomeres

Hepatic glucose production (HGP) normally begins just prior to birth. Prolonged fetal hypoglycemia, intrauterine growth restriction, and acute hypoxemia produce an early activation of fetal HGP. To test the hypothesis that prolonged hypoxemia increases factors which regulate HGP, studies were performed in fetuses that were bled to anemic conditions (anemic: n = 11) for 8.9 ± 0.4 days and compared with control fetuses (n = 7). Fetal arterial hematocrit and oxygen content were 32% and 50% lower, respectively, in anemic vs. controls (P < 0.005). Arterial plasma glucose was 15% higher in the anemic group (P < 0.05). Hepatic mRNA expression of phosphonenolpyruvate carboxykinase (PCK1) was twofold higher in the anemic group (P < 0.05). Arterial plasma glucagon concentrations were 70% higher in anemic fetuses compared with controls (P < 0.05), and they were positively associated with hepatic PCK1 mRNA expression (P < 0.05). Arterial plasma cortisol concentrations increased 90% in the anemic fetuses (P < 0.05), but fetal cortisol concentrations were not correlated with hepatic PCK1 mRNA expression. Hepatic glycogen content was 30% lower in anemic vs. control fetuses (P < 0.05) and was inversely correlated with fetal arterial plasma glucagon concentrations. In isolated primary fetal sheep hepatocytes, incubation in low oxygen (3%) increased PCK1 mRNA threefold compared with incubation in normal oxygen (21%). Together, these results demonstrate that glucagon and PCK1 may potentiate fetal HGP during chronic fetal anemic hypoxemia.

Topics: Anemia; Animals; Female; Fetal Hypoxia; Fetus; Glucagon; Glucose-6-Phosphatase; Glycogen; Hepatocytes; Hydrocortisone; Hypoxia; Liver; Organ Size; Phosphoenolpyruvate Carboxykinase (GTP); Pregnancy; RNA, Messenger; Sheep; Umbilical Cord

Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine several end-points to determine if the metabolic stress affects the developing brain. The uterine artery and uterine branch of the ovarian artery were occluded with aneurysm clamps for a period of 45 min, the clips removed and the metabolites in five regions of the perinatal brain were measured at 0, 2 and 6 h of reflow. Regional P-creatine, ATP and glucose levels were significantly depleted at the end of the 45 min occlusion. The levels of glycogen and glutamate at the end of the occlusion indicated a decreasing trend which was not significant. The concentration of citrate remained essentially unchanged at the end of the occlusion. To ensure that the insult was not lethal to the tissue, the recovery of the metabolites was examined at 2 and 6 h of reflow and generally the concentrations of the high-energy phosphates and glucose were normal or near-normal by 6 h of reperfusion in the five regions of the brain examined. The changes in the metabolites indicate that 45 min of hypoxia/ischemia is an appropriate model for studying neonatal development after fetal metabolic stress.

Topics: Adenosine Triphosphate; Animals; Brain; Creatine; Disease Models, Animal; Female; Fetal Hypoxia; Glucose; Glycogen; Hypoxia-Ischemia, Brain; Lactic Acid; Phosphates; Pregnancy; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Uterus

Most frequently, placental glycogen has been studied as an index of fetal nutrition. There are no published studies of placental glycogen as an index of fetal stress. In this study of 1573 samples from 71 placentae, glycogen levels in the placental disk, fetal membranes and umbilical cord of normal uncomplicated pregnancies were compared with those in complicated pregnancies. The complicated pregnancies included preterm delivery, hypertensive disorders, inadequate prenatal care, substance abuse, maternal fever or infection, obesity, diabetes mellitus, premature rupture of membranes, intrauterine growth retardation, sickle cell trait, and acute meconium staining of amniotic fluid at delivery. The data showed that the only significant differences were in the subgroup complicated by meconium-stained amniotic fluid in which the placental disks and umbilical cords had significantly lower (P=0.0006) glycogen levels. This finding suggests a relatively specific association. It is interesting to speculate that the passage of meconium with its vasoconstrictive effect increases utilization of local glycogen stores, decreases local glycogen reserves needed for the work of further vasoconstriction, and, in the event of subsequent acute stress, impairs vascular perfusion of tissues. In this way, meconium could predispose the infant to asphyxia.

Topics: Amniotic Fluid; Case-Control Studies; Extraembryonic Membranes; Female; Fetal Hypoxia; Fetus; Glycogen; Humans; Infant, Newborn; Male; Meconium; Placenta; Pregnancy; Pregnancy Complications; Umbilical Cord; Vasoconstriction

Rat fetal brain glycogen content, and glycogen synthase and phosphorylase activities were measured both in control and in hypoxia on 17th, 19th and 21st days of gestation. Glycogen distribution in the brain was also observed with an optical microscope. The results obtained were as follows: 1. Glycogen content was highest in the choroid plexus, and there tended to be located more in the periventricular areas and hemispheric surface layers of the cerebrum than in other areas. 2. Glycogen content increased from the 17th day, reaching a peak on the 19th day; it decreased with age thereafter and had decreased significantly by the 21st day. 3. Glycogen synthase a-type activity showed no change with fetal age. 4. Glycogen phosphorylase activity was lowest on the 17th day, and it increased thereafter with age. 5. When an ischemic load was applied, brain glycogen content decreased and glycogen phosphorylase a-type activity increased on the 17th and 19th days. The abovementioned findings suggest that glycogen in the rat fetal brain is distributed in the most likely sites of intracranial hemorrhage. The amount of glycogen in the rat fetal brain may depend on glycogen phosphorylase activities. Glycogen may be used as an energy source to maintain brain tissue function during hypoxia. It is also possible that glycogen plays a role in brain maturation.

Topics: Animals; Brain; Brain Chemistry; Female; Fetal Hypoxia; Gestational Age; Glycogen; Glycogen Synthase; Lactates; Phosphorylases; Pregnancy; Rats; Rats, Inbred Strains

Myocardium has been investigated in 68 human fetuses and newborns suffered from intrauterine acute and prolonged hypoxia, occurred as a result of various maternal, fetal and placental diseases. Under acute hypoxia only reactive changes of the contractile myocardium appear. They are demonstrated as degeneration of muscle fibers and appearance of scattered foci of necrosis in cardiomyocytes. Under a prolonged hypoxia, besides analogous reactive changes, compensatory hypertrophy of some part of cardiomyocytes is noted; this is manifestation of a compensatory-adaptive reaction of the myocardium.

Topics: Asphyxia Neonatorum; Coronary Vessels; Female; Fetal Hypoxia; Glycogen; Glycosaminoglycans; Humans; Microcirculation; Myocardium; Pregnancy

Topics: Animals; Blood Glucose; Dogs; Female; Fetal Blood; Fetal Heart; Fetal Hypoxia; Glycogen; Heart Rate; Hydrogen-Ion Concentration; Oxygen Consumption; Pregnancy; Shock, Hemorrhagic

8 term fetal pigs (110-112 days gestation) and one 97-day fetus were asphyxiated in utero by occlusion of the umbilical cord. Mean times to last gasp and last heart beat were 5.1 and 22.4 for term and 5.4 and 30.4 min for the 97-day fetus. Cord occlusion was followed by profound bradycardia and an increase in blood pressure which was maintained until gasping ceased. Profound acidemia, hypercapnia and hyperlactacidemia developed in all animals and values following asphyxiation were comparable with those seen in stillborn piglets. Liver and cardiac glycogen levels were lower in asphyxiated fetuses than in littermates but muscle glycogen levels were similar in both groups.

Topics: Animals; Blood Glucose; Blood Pressure; Female; Fetal Hypoxia; Glycogen; Heart Rate; Hematocrit; Hydrogen-Ion Concentration; Lactates; Liver Glycogen; Muscles; Partial Pressure; Pregnancy; Respiration; Swine

Cerebral oxidative metabolism during intrauterine growth retardation was investigated utilizing a pregnant-rat model. Dams were subjected to unilateral uterine artery ligation on the 17th day of gestation. At term, they were sacrificed by decapitation and the fetuses delivered by cesarean section. Body and brain weights of fetuses from ligated uterine segments were smaller than those of offspring from nonligated horns of the experimental rats or those from sham-operated dams. Blood glucose at birth was reduced by 25% in growth-retarded fetuses. Cerebral oxidative metabolites, including glycogen, glucose, lactate, ATP, and phosphocreatine, were not different from control levels. These findings suggest that neither tissue hypoxia nor deficient glucose delivery to brain can account for the stunted cerebral growth observed in fetuses following uterine artery ligation.

Topics: Adenosine Triphosphate; Animals; Body Weight; Brain; Female; Fetal Growth Retardation; Fetal Hypoxia; Glucose; Glycogen; Lactates; Organ Size; Oxygen Consumption; Phosphocreatine; Pregnancy; Rats

The isometric contraction of the isolated rabbit myocardium was measured from 24 days post coitum (dpc) to young adulthood. Tension per gram of heart as developed by the isolated perfused hearts remained constant during late foetal life but increased during the first postnatal week. Sensitivity to hypoxia rapidly increased during foetal life from 26 to 28 days post coitum. In young foetal hearts (up to 28 days post coitum), contraction continued for several hours in the absence of glucose. In contrast, from 28 days post coitum onwards foetal hearts became increasingly dependent on external glucose to maintain their contractility. This change was concomitant with a decrease in myocardial glycogen content. Intracellular electrical activity recorded in the absence of glucose showed that during hypoxia in the foetus at term were reduced, whereas normal activity continued in the same hypoxic glucose-free medium in hearts from foetuses 26 days post coitum. The relative role of glycolysis and oxidative metabolism is discussed and the importance of glycogenolytic metabolism in young isolated foetal hearts is pointed out.

Topics: Animals; Asphyxia Neonatorum; Female; Fetal Hypoxia; Glucose; Glycogen; Heart; Humans; Hypoxia; Infant, Newborn; Myocardial Contraction; Myocardium; Perfusion; Pregnancy; Rabbits

The glycogen contents of 121 rabbit brains having different levels of hypoxia were determined, calculation being in mg% of glucose per g of brain. It was possible to observe significant reductions in carbohydrate content under conditions of acute and chronic hypoxia. Moderate prepartum accumulation of glycogen in untreated rabbit brains is likely. Chronic reduction in reserve fuel resulted in deficient development of the brain, as is clearly shown by brain weight determinations. This enables a parallel between this condition and intrauterine dystrophia.

Topics: Animals; Animals, Newborn; Brain; Disease Models, Animal; Female; Fetal Hypoxia; Glycogen; Hypoxia; Organ Size; Pregnancy; Rabbits