Effect of vitamin E on the response of lung antioxidant enzymes in young rats exposed to hyperoxia.
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Biomedical subjects
Publications and source records attributed to H Obara.
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In rabbit pulmonary artery, dopamine (10(-11)-10(-5) M) produced a concentration-dependent relaxation of the arterial strips contracted with prostaglandin F2 alpha (PGF2 alpha) in the presence of prazosin (10(-6) M), yohimbine (10(-6) M), propranolol (10(-6) M), and methysergide (10(-6) M). SKF38393, an agonist for D1 or DA1 dopamine receptor, mimicked partially the concentration-response curve for dopamine, whereas LY171555 and apomorphine did not. The order of potency of dopamine antagonists on the inhibitory effect was: cis-flupenthixol greater than bulbo-capnine greater than metoclopramide greater than haloperidol. Sulpiride was inactive. Cis-flupenthixol did not block the relaxation induced by acetylcholine, adenosine, and papaverine. In the arterial strips of the rabbits pretreated with 6-hydroxydopamine, the concentration-response curve for dopamine was similar to that in non-treated rabbits. Thus it is concluded that a specific dopamine receptor is located on the postsynaptic muscle membrane of the rabbit pulmonary artery.
We applied positive end expiratory pressure to the nondependent, nonventilated lung, or both nondependent and dependent, ventilated lung during one lung anaesthesia, and compared the results to those obtained by other techniques, such as increasing the inspired oxygen concentration in the dependent lung, or insufflating with oxygen using positive end expiratory pressure in the nondependent lung. Our study suggests that arterial oxygenation and intrapulmonary shunt can be lessened during one lung ventilation by continuous oxygen insufflation of the nondependent lung at 0.98 kPa positive end expiratory pressure while the dependent lung is ventilated with 0.49 kPa positive end expiratory pressure.
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We measured plasma levels of vitamin E (total tocopherol) and lipoperoxide in seventeen neonates (less than 10 days), twenty infants (1-12 months) and ten children (1-5 years) during anaesthesia. The seventeen neonates were randomly divided into two groups; seven who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly before anaesthesia and ten who did not. The 20 infants were divided into three groups: Group 1: eight infants who did not receive vitamin E; Group 2: six who received 30 mg X kg-1 of alpha-tocopheryl acetate orally for three days before anaesthesia; Group 3: six who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly three hours before anaesthesia. In the neonates who did not receive alpha-tocopheryl acetate, plasma vitamin E and lipoperoxide levels were unchanged following surgery. In Group 1 infants, plasma vitamin E levels decreased (p less than 0.05) and plasma lipoperoxide levels increased (p less than 0.05). In both neonates who received vitamin E and Group 3 infants the mean plasma vitamin E levels increased significantly (p less than 0.05) following surgery. In Group 2 infants, the levels of plasma vitamin E before surgery were high, as compared to the other groups: however, plasma vitamin E levels decreased following surgery. In the children, the plasma vitamin E levels were unchanged, while the plasma lipoperoxide levels decreased significantly (p less than 0.05) during anaesthesia. It is suggested from our studies that plasma vitamin E levels decrease and plasma lipoperoxide levels increase during anaesthesia and surgery in infants; however, those levels are unchanged in neonates.
Prolonged inhalation of 80% oxygen, in contrast to 100% oxygen, has generally been assumed not to lead to significant pulmonary impairment. Two and six week old C57BL mice were systematically assessed by transmission and scanning electron microscopy for structural changes in the lung caused by inhalation of 80% and 100% oxygen from the first day of life, and the injury was quantitated morphometrically. Six weeks of continuous inhalation of 80% oxygen resulted in diffuse fibrosis of the gas exchanging parts of the lung superimposed on which were, in the 100% oxygen exposed mice, foci of coarse scarring. Lowering the inspired oxygen concentration from 100% to 80% appeared to reduce the mucosal injury more than the interstitial fibrotic response. This suggests that the most persistent alteration caused by chronic supplemental oxygen exposure below 80% will be interstitial fibrosis.
We compared rapid-rate ventilation using a conventional ventilator with slow-rate ventilation in the normal lung of 7 newborn pigs and in the diseased lung model instilled with 25% meconium solution into the trachea. The flow rate (7.5 1/min) and inspiratory:expiratory ratio (1:3) were kept constant during the experiments by using a constant-flow and time-cycled ventilator; the only change in settings was the rate. Transthoracic electrical impedance at end-expiration increased in the normal and in the diseased lung. Both mean intratracheal pressure and end-expiratory esophageal pressure increased significantly (p less than 0.05) in both models upon changing to rapid-rate ventilation. Following the increase in ventilatory rates from an initial frequency of 37.5 breaths/min to a rapid rate of 150 breaths/min, there was a significant rise in both PaO2 and PaCO2 in the normal and diseased lung models. Although rapid-rate ventilation was maintained for 1 h, the improvement in oxygenation progressively deteriorated and PaCO2 also increased further. This rise in PaCO2 returned to the control levels by decreasing ventilation to the initial rate of 37.5/min. This study demonstrates that rapid-rate ventilation using a constant-flow and time-cycled ventilator is inferior to slow-rate ventilation in the diseased lung model.
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We measured plasma cortisol levels during surgery in seven neonates within ten days after birth and in 14 infants ranging in age from three months to 11 months. The 14 infants were divided into two groups; Group I included eight infants in whom general anaesthesia was maintained with oxygen, nitrous oxide and a muscle relaxant, Group II, six infants in whom general anaesthesia was maintained with oxygen, nitrous oxide, halothane and a muscle relaxant. In the neonates, the changes in mean plasma cortisol levels during anaesthesia were not statistically significant. In both Group I and Group II infants, the mean cortisol levels gradually rose during anaesthesia, but the initial rise in plasma cortisol levels was suppressed in the patients who received halothane.
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Continuous exposure of newborn C57BL mice to 80% oxygen at normal atmospheric pressure for as many as 6 weeks results in significant pulmonary injury. This injury is reflected morphometrically and morphologically primarily in an increase in the pulmonary interstitial compartment and in pulmonary fibrosis. The fibrotic response is both peribronchiolar and parenchymal. Lowering the oxygen concentration of continuous exposure from 100 to 80% appears to reduce the cellular response of the alveolar lining cells and the bronchiolar mucosa in the newborn lung more than the fibrotic response. This suggests that the most persistent response in the growing lung to supplemental oxygen concentrations at or below 80% will be peribronchiolar and parenchymal fibrosis. These findings would account for the clinically observed reduction of stage II bronchopulmonary dysplasia, yet persistence of chronic bronchopulmonary dysplasia in human infants treated with supplemental oxygen concentrations below 100%.
We have studied the effects of inhalation of 95 to 100% oxygen on the surface morphology of the bronchi and bronchioles of adult mice, using scanning electron microscopy. Denudation of cilia and truncation of the remaining cilia were commonly observed during high oxygen exposure. Bleb formation, a "moth-eaten" appearance of the non-ciliated cell surface and desquamation of unidentified cells were present in the bronchus after 96 hours of oxygen exposure. Deformation of non-ciliated cells, denudation of cilia, and flattening of the luminal surface were also seen in the bronchiole. For studying the recovery process from acute oxygen damage, we returned mice to room air after four days of high oxygen inhalation and killed them four, seven and 15 days after. There were more variable and complex changes of surface morphology in individual mice during the recovery phase. We observed flattening of the epithelial surface in the bronchiole and bronchus, and noticed that deformation of non-ciliated cells were seen even after 15 days. High oxygen inhalation causes severe morphological changes in the bronchial and bronchiolar mucosa, and those morphological lesions remain for at least two weeks after cessation of oxygen inhalation.
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Alkaline phosphatase was brought into solution from microsomal fractions of placentas of varying gestational age by using gradually increasing concentrations of proteinase papain. When the activity of the soluble alkaline phosphatase (S) was compared with that of the non-soluble residue (R), the S/R ratio rose as pregnancy progressed. The electrophoretic pattern showed that in serum from pregnant women the papain-soluble alkaline phosphatase corresponded to the heat-stable one. These results indicate that the cytoplasmic membrane of the trophoblast changes with the growth of the placenta so that this enzyme is easily dissolved by papain. It is probable that alkaline phosphatase molecules easily enter the maternal blood stream in late pregnancy.
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