Cerebral excitatory amino acids and Na+, K+-ATPase activity during resuscitation of severely hypoxic newborn piglets

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.     

Vitamin E and liver damage in MZ heterozygous infants with alpha1-antitrypsin deficiency

Low levels of alphal₁-antitrypsin can predispose affected infants to develop a wide spectrum of liver diseases. Heterozygous PiMZ carriers can be affected by a subclinical liver involvement in the first six months of life. The liver damage appeals to be mediated by the activity of toxic oxygen waste products originating from partially unchecked proteases which can cause enough damage to impair hepatic function significantly. In the present study it was found that the antioxidant properties of vitamin E were able to reduce the frequency of liver dysfunction in PiMZ carriers at two but not at five months of age. Liver damage is highly related to low levels of alpha-tocopherol in the plasma. These findings show that oxidative free radicals can promote liver damage in inadequately protected young infants, such as those affected by alpha,-antitrypsin deficiency. The protective role of vitamin E in relation to the developmental expression of other antioxidant scavengers is discussed.     

THE INFLUENCE OF CHANGES IN ARTERIAL BLOOD PRESSURE ON TRANSCUTANEOUS OXYGEN TENSION (tcPO2) IN THE NEWBORN

ABSTRACT. The possible artefacts in transcutaneous oxygen tension (tcP_O2) induced by fluctuations in arterial blood pressure were investigated in ten newborn babies. We mounted one tcP_O2 electrode on the foot and another on the chest, and the local arterial blood pressure under the foot electrode was reduced 0.6-2.0 kPa (9-15 mmHg) by elevating the foot 11-19 cm above the heart level. In five mature newborns the tcP_O2 of the foot decreased significantly ( p =0.015) during elevation by a mean valve of 0.029 kPa (0.22 mmHg) per mmHg decrease in mean arterial blood pressure. In five premature newborns the artefact was insignificant ( p =0.62). We conclude therefore that, in contrast to adults, the artefacts induced by minor fluctuations in arterial blood pressure in newborns are hardly of clinical importance.     

Relationship between PaO2 and Lung Volume during High Frequency Oscillatory Ventilation

The relationship between oxygenation and lung volume during high frequency oscillatory ventilation (HFOV) was studied. We ventilated anesthetized, tracheostomized adult rabbits that were rendered surfactant-deficient by lung lavage. Lung volume was measured by the 'disconnection technique'. In the first experiment, HFOV was commenced after conventional mechanical ventilation (CM V) for 1 hr. In the absence of sustained inflation (SI), oxygenation improved with time during HFOV. In the second experiment, HFOV was instituted after CMV for 4hr. In the absence of SI, all animals expired during the experimental period. In the third experiment we ventilated rabbits for 4 hr and then switched to HFOV. We applied SI first and increased mean airway pressure (MAP) by increments of 2 cmH₂O every 15 min. However, there was little improvement in Pa_O2 despite the use of repeated SI and the increase in MAP. We conclude that oxygenation has a linear relationship to lung volume during HFOV, and that secondary lung injury due to long-term CMV impairs the response to HFOV. Therefore, it is important to minimize the risk of such secondary injuries before instituting HFOV.     

EFFECTS OF AN ANTENATAL LOAD OF PYRIDOXINE (VITAMIN B6) ON THE BLOOD OXYGEN AFFINITY AND PROLACTIN LEVELS IN NEWBORN INFANTS AND THEIR MOTHERS

ABSTRACT. The effects of a loading dose of pyridoxine (100 mg) given intramuscularly or per os to 24 earlier non-supplemented pregnant women at term was investigated. The in vitro oxygen affinity (P₅₀) and the prolactin level in both maternal and newborn blood was sampled. The blood P₅₀ values were measured by a variant of "mixing method". Blood prolactin levels were determined by RIA. After pyridoxine administration, the maternal P₅₀ values increased moderately and the newborns' cord blood P₅₀ values increased significantly when compared with the control group's (number of cases 12) values. The decrease of blood oxygen affinity was most pronounced in the supplemented groups in newborns' capillary blood at the age of five days. The pyridoxine supplementation had no effect on the maternal and the newborns' cord blood prolactin level or on the daily amount of breast milk. Pyridoxine supplementation of the mother at labour may influence favourably the oxygen transport function of the newborn's blood and it may be especially advantageous in early postnatal adaptation disturbances of newborns.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

Altered Na+-K+ ATPase activity in uraemic adolescents

The Na⁺-K⁺ ATPase enzyme plays an essential role in the regulation of cell composition and volume. Enzyme activity itself is regulated by substrate availability and several hormones. In adult uraemic patients red blood cell Na⁺-K⁺ ATPase activity is decreased. However, it is unknown if children with uraemia exhibit the same phenomenon. Therefore, in the present study we examined whether endogenous digoxin-like factors (EDLF) and physicochemical membrane properties play a role in the regulation of erythrocyte Na⁺-K⁺ ATPase activity in uraemic children and adolescents. Healthy age-matched children were used as controls. Enzyme activity was measured in detergent-pretreated red blood cells and erythrocyte ghosts. Na⁺-K⁺ ATPase activity (2204 ± 538nmol Pi ml erythrocyte^?1 h^?1 in detergent pretreated erythrocytes; 204 ± 56 nmol Pi mg protein^?1 h^?1 in ghosts) in adolescents with uraemia was lower compared to controls (3245 ± 362 nmol Pi ml erythrocyte ¹ h^?1; 266 ± 37 nmol Pi mg protein^?1 h^?1, p < 0.001, p < 0.05, respectively). Plasma levels of EDLF were elevated in uraemic patients (0.30 ± 0.05 versus 0.21 ±0.04 ng ml^?1, p < 0.01). Furthermore, the membrane lipid component was decreased in patients with uraemia, while the cholesterol/phospholipid ratio and membrane fluidity were similar in both groups. No correlation was found between the decrease in Na⁺-K⁺ ATPase and the increase in EDLF concentration and altered membrane lipid components. Our results demonstrate, that similar to the findings of adults, the activity of Na⁺-K⁺ ATPase is diminished in uraemic adolescent patients, and that uraemia-associated elevation in EDLF and altered membrane components do not play a role in the down-regulation of Na⁺-K⁺ ATPase. Therefore other factors (presence of other inhibitors and/or reduced number of enzyme molecules) should contribute to the lower activity of the Na⁺-K⁺ pump.     

BALANCED (2q-; 14q+) TRANSLOCATION

A child presented at 6 years of age with virilization presumed due to maternal progesterone therapy during pregnancy. She was found to have a balanced translocation involving chromosomes 2 and 14.     

Cytochrome B558 Component of O-2M Generating Oxidase in the Neutrophils From Patients With Chronic Granulomatous Disease

Cytochrome b₅₅₈ is probably a component of an electron transport chain which is called NADPH oxidase. Cytochrome b₅₅₈ from the neutrophils of two male patients with chronic granulomatous disease (CGD) and their parents was studied. One of the CGD patients had decreased amounts of cytochrome b₅₅₈, The α-band of light absorption of cytochrome b₅₅₈ at 558 nm was found as a trace, and the peak of the γ-band was shifted to 420 nm, whereas the normal γ-band is at 426 nm. Intermediate amounts of cytochrome b₅₅₈ were present in his mother, whereas his father had a normal amount. Another patient had normal peaks of α- and γ-bands of cytochrome b₅₅₈. Thus, abnormalities in NADPH oxidase of the two patients were different.     

Survival of Cr51-labelled Red Cells from New-born Infants1

Summary
The survival of Cr⁵¹-labelled placental red cells of 10 full-term and 6 premature infants was studied after transfusion to adult recpients. The mean apparent half-life of the red cells from full-term infants was found to be 22.8 days, and that of red cells from premature infants 15.8 days (cf. 27.5 days for red cells from adults). Results obtained by others using the differential agglutination method have indicated a longer life span than that corresponding to the Cr⁵¹ half-times above mentioned. The most probable explanation of this difference seems to be that Cr⁵¹ is eluted more rapidly from fetal red cells than from red cells of adults. This hypothesis is corroborated by the results of experiments in vitro on intact red cells.