Effect of Resuscitation with 21% Oxygen and 100% Oxygen on NMDA Receptor Binding Characteristics Following Asphyxia in Newborn Piglets
Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA.Neurochemical Research (Impact Factor: 2.59). 08/2007; 32(8):1322-8. DOI: 10.1007/s11064-007-9307-z
The present study investigated the effect of reventilation with 21% and 100% oxygen following asphyxia in newborn piglets on NMDA receptor binding characteristics, Na(+), K(+)-ATPase activity, and lipid peroxidation. After achieving a heart rate less than 60 beats per minute, asphyxiated piglets were reventilated with 21% oxygen or 100% oxygen. (3)[H]MK-801 binding showed the Bmax in the 21% and 100% groups to be 1.53 +/- 0.43 and 1.42 +/- 0.35 pmol/mg protein (p = ns). Values for Kd were 4.56 +/- 1.29 and 4.17 +/- 1.05 nM (p = ns). Na(+), K(+)-ATPase activity in the 21% and 100% groups were 23.5 +/- 0.9 and 24.4 +/- 3.9 micromol Pi/mg protein/h (p = ns). Conjugated dienes (0.05 +/- 0.02 vs. 0.07 +/- 0.03 micromol/g brain) and fluorescent compounds (0.54 +/- 0.05 vs. 0.78 +/- 0.19 microg quinine sulfate/g brain), were similar in both groups (p = ns). Though lipid peroxidation products trended higher in the 100% group, these data show that NMDA receptor binding and Na(+), K(+)-ATPase activity were similar following reventilation with 21% or 100% oxygen after a single episode of mild asphyxia.
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ABSTRACT: We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O2 supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n = 8), 21% O2 (n = 8), and 100% O2 groups (n = 8). The hypoxaemic group was mechanically ventilated with 12-18% O2 adjusted to achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%, mean +/- SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p = 0.044 and p = 0.055, respectively) than during resuscitation with 21% O2 or 100% O2, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na+,K+-ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups (p = 0.30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O2. Resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.Acta Paediatrica 09/1998; 87(8):889-95. DOI:10.1111/j.1651-2227.1998.tb01557.x · 1.67 Impact Factor
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ABSTRACT: The present study tests the hypothesis that ventilation with 100% O2 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21% oxygen. This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model. Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extra-cellular levels of dopamine and its metabolites by in vivo microdialysis. After establishment of a baseline, both the fraction of inspired oxygen (FiO2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period. For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen. It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls. During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21% oxygen (19 vs. 11 torr). During the first hour of reoxygenation, extracellular dopamine levels decreased to approximately 200% of control in the 21% oxygen group, whereas these levels were still much higher in the 100% oxygen group (approximately 500% of control). After approximately 2 h of reoxygenation, there was a secondary increase in extracellular dopamine to approximately 750 and approximately 3,000% of baseline for the animals ventilated with 21 and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)Journal of Neurochemistry 02/1995; 64(1):292-8. DOI:10.1016/0300-9572(95)94122-P · 4.28 Impact Factor
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ABSTRACT: The effect of hypoxia on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the brain cell membrane of the newborn piglet was studied. Experiments were conducted on newborn piglets, 2-4 days of age, that were anesthetized and mechanically ventilated. Hypoxic hypoxia was induced in the experimental group by lowering the FiO2 to 5-7%. The control group was ventilated under normoxic conditions. Tissue hypoxia was documented biochemically by decreased levels of ATP and phosphocreatine (PCr) in the hypoxic group (52% and 81% lower than the normoxic group, respectively). [3H]MK-801 binding characteristics (Bmax = number of receptors, Kd = dissociation constant) were used as an index of NMDA receptor modification. In hypoxic brains, Bmax decreased from the control level of 1.13 +/- 0.15 pmol/mg protein to 0.68 +/- 0.23 pmol/mg protein (P < 0.01) and the Kd value decreased (reflecting increased affinity) from 9.46 +/- 1.68 nM in the control brains to 4.87 +/- 1.42 nM (P < 0.01) in the hypoxic brains. The Na+,K(+)-ATPase activity, an index of brain cell membrane function, decreased from a control value of 46.5 +/- 0.4 to 40.5 +/- 2.3 mumol inorganic phosphate (Pi) mg protein/h (P < 0.005) during hypoxia. The results of this study indicate that hypoxia in newborn piglets modifies the NMDA receptor in the cerebral cortex, resulting in an increased affinity of the receptor channel. Hypoxia-induced modification of the NMDA ion/receptor complex may be a potential mechanism of cerebral excitotoxicity.Neuroscience Letters 03/1994; 167(1-2):156-60. DOI:10.1016/0304-3940(94)91051-0 · 2.03 Impact Factor
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