Postnatal physiological development of rats after acute prenatal hypoxia

The aim of study was to investigate the physiological development of the brain and behaviour in rats subjected to prenatal hypoxia on the 13.5th day of embryogenesis. We have found that such rats manifested a delayed physiological development and a change in nervous tissue of the sensorimotor cortex, as well a disturbed formation of motor responses during the first month of postnatal ontogenesis. During maturation these modifications were in part compensated, however we observed a decrease of the rats' ability to learn new forepaw movements. The destruction of the brain tissue and the modification of neurons composition in the sensorimotor cortex correlated with changes of behaviour at different stages of ontogenesis. Thus, changes of the conditions under which an organism develops during embryogenesis, predetermine a disturbance in ontogenesis and the learning ability.     

Excitability changes of cortical neurons during the postnatal period in rats exposed to prenatal hypobaric hypoxia

Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed.     

Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.     

LHRH and LH in peripubertal female rats following prenatal and/or postnatal ethanol exposure

The effects of pre- and postnatal exposure to ethanol (ETOH) on LHRH and LH were investigated. Pregnant and/or lactating dams were fed ETOH during: 1) gestation, 2) lactation, or 3) gestation-lactation. Female offspring were decapitated at 30 or 40 days-of-age; trunk blood was collected for plasma LH RIA; and hypothalamic tissues were collected for LHRH RIA. Hypothalamic LHRH content of all ETOH-exposed groups was less than that of non-ETOH-fed controls at 30 and 40 days-of-age (p less than 0.05). Plasma LH concentrations of all ETOH-exposed groups were less than those of non-ETOH-fed controls at 30 and 40 days-of-age (p less than 0.05). Also, at 30 and 40 days-of-age, the plasma LH concentrations of the animals exposed to ETOH during lactation and gestation-lactation were less than those of the animals exposed to ETOH during gestation (p less than 0.05). These data suggest that ETOH exposure during gestation and/or lactation negatively affects hypothalamic LHRH content of female rat offspring. Decreased hypothalamic LHRH content with corresponding lowered plasma LH concentration suggests that ETOH influences development or maturation of hypothalamic LHRH neurons by possibly decreasing their number or synthesizing capability.     

Respiratory adaptation to chronic hypoxia in newborn rats

Newborn rats were maintained in an hypoxic chamber (10% O2 in N2) from the day of birth up to 2 wk of postnatal life. Body weight (BW) and nose-tail length were less in the hypoxic exposed (H) rats than in control (C) animals growing in air. Hematocrit rose from about 37% to about 51%. Oxygen consumption (VO2), measured with a manometric method, was lower in H than in C rats; the difference remained at 5-7 days even after normalization by BW. At 5-7 days ventilation, measured with an airflow plethysmograph, was much more elevated in H rats (whether breathing 10% O2 or air) than in C rats, with an increase in both tidal volume and frequency. This indicates that the biphasic ventilatory response, characterized by an initial rise and then a fall of ventilation toward normoxic values, commonly observed in newborns during acute hypoxic challenge is an immediate but only transient response. The dry lung weight-to-BW ratio and alveolar size were larger in H than in C rats. Lung volumes at 20 cmH2O were similar, despite the smaller BW of the H rats. Hence, in the rat, chronic hypoxia in the immediate postnatal period increases O2-carrying capacity, decreases metabolic demands, increases alveolar O2 availability, and promotes structural changes in the lung that protect the gas exchange area and optimize the structure-function relationship of the lung. These results may also suggest that the lung structural alterations with chronic hypoxia should not be attributed to changes in VO2 but, eventually, to the ventilatory action of the organ.     

Compliance of the respiratory system in newborn and adult rats after gestation in hypoxia

We hypothesized that hypoxia during gestation modifies the compliance of the respiratory system of newborn and adult rats. Pregnant rats were placed in a hypobaric chamber at an inspired oxygen pressure of 86 mmHg (equivalent to 12% O₂ in normobaria) from day 4 of gestation until day 2 post-partum. Three- day-old rat pups were smaller than controls, with higher hematocrit; the lungs were also small, with less protein and DNA content. The pressure (x-axis)-volume (y-axis) curve of the respiratory system was displaced to the right of the control curve, and the compliance of the respiratory system, measured on the inflation or deflation limb of the pressure-volume curve, was decreased by ∼20–25%, depending upon the normalization procedure (per body mass or per dry lung weight). In 50-day-old rats exposed to hypoxia during gestation, body weight, hematocrit, lung mass and DNA content were normal; the compliance of the respiratory system, measured at ventilation frequencies between 20 cpm and 100 cpm, was higher than in controls by ∼20%. It is concluded that the effects of prenatal hypoxia on the compliance of the respiratory system can vary with age. In the rat the process of alveolar formation initiates postnatally. Hence, in the newborn the effects of the prenatal hypoxia on the compliance of the respiratory system are likely to be dominated by the hypoxic pulmonary hypoplasia and hypertension, which decrease the compliance of the respiratory system. In the adult, the effects of the decreased alveolar formation are the prevailing ones, increasing the compliance of the respiratory system. Accepted: 3 January 2000     

Electrical activity of the neocortex in adult rats after prenatal hypoxia and in epilepsy model

Changes in electrical activity of the neocortex after prenatal hypoxia (day 14 of embryogenesis, E14, 7% O₂ for 3 h) and intracortical microinjection of epileptogenic 4-aminopyridine (4-AP) were studied in adult (3-month-old) rats. The frequency–time parameters of electrocorticogram (ECoG) were analyzed during sleep and wakefulness as well as in a model of 4-AP-induced spike-wave discharge (SWD) epileptiform activity. The results showed that in rats exposed to prenatal hypoxia the theta rhythm had a lower frequency while sleep spindles displayed a lower spectral power in the low-frequency range as compared to the control group. In rats with prenatal pathology, there was revealed a delayed onset of epileptiform activity and a shifted frequency distribution of the SWD spectral power induced by 4-AP.     

Effect of prenatal hypoxia during organogenesis on albino rat behavior during postnatal period

The survival rate, physical development, and spontaneous behavior has been evaluated in pups of albino rats exposed to acute hypobaric hypoxia on the 9–10th day of gestation corresponding to the onset of organogenesis. Prenatal hypoxia increased the mortality among the offspring, delayed their physical development, and affected their spontaneous behavior up to the age of 2 months. The females exposed to intrauterine hypoxia proved to be more sensitive to hypoxia than males.     

Long-term effect of postnatal hypoxia on the seizure susceptibility in rats

The effects of postnatal hypoxia at ten days of age on the pentylenetetrazol (PTZ)-induced seizure and amygdaloid kindling were investigated in male adult rats. The rats with postnatal hypoxia were significantly more susceptible to PTZ and had a significantly more easily induced amygdaloid kindling with a rapid propagation of afterdischarges to the contralateral amygdala than the control group. Light microscopic examination in one adult rat brain with postnatal hypoxia revealed no abnormal histopathological changes. The present study suggests that the consequences of postnatal hypoxia in rats remain for a long time as enhancement in seizure susceptibility.     

Morphofunctional and biochemical properties of erythrocytes in early postnatal ontogenesis in rats in norm and after prenatal stress

Morphofunctional and biochemical properties of erythrocyte membrane were investigated in early postnatal ontogenesis in rats in norm and after prenatal immobilization stress. The transient decrease of erythrocyte membranes stability was revealed in the control rats. The ability to erythrocyte transformation and the concentration of lipid peroxidation products are increased. It has been shown by an increase of percentage discocytes and lower lipid peroxidation level that the erythrocyte membrane of the rats after prenatal stress is more stable.     

Quantification of compensatory processes of postnatal hypoxia in newborn piglets applying short-term nonlinear dynamics analysis

Background

Acute Respiratory Distress Syndrome (ARDS) patients require mechanical ventilation (MV) for breathing support. Patient-specific PEEP is encouraged for treating different patients but there is no well established method in optimal PEEP selection.

Methods

A study of 10 patients diagnosed with ALI/ARDS whom underwent recruitment manoeuvre is carried out. Airway pressure and flow data are used to identify patient-specific constant lung elastance (E _lung ) and time-variant dynamic lung elastance (E _drs ) at each PEEP level (increments of 5cmH ₂ O), for a single compartment linear lung model using integral-based methods. Optimal PEEP is estimated using E _lung versus PEEP, E _drs -Pressure curve and E _drs Area at minimum elastance (maximum compliance) and the inflection of the curves (diminishing return). Results are compared to clinically selected PEEP values. The trials and use of the data were approved by the New Zealand South Island Regional Ethics Committee.

Results

Median absolute percentage fitting error to the data when estimating time-variant E _drs is 0.9% (IQR = 0.5-2.4) and 5.6% [IQR: 1.8-11.3] when estimating constant E _lung . Both E _lung and E _drs decrease with PEEP to a minimum, before rising, and indicating potential over-inflation. Median E _drs over all patients across all PEEP values was 32.2 cmH ₂ O/l [IQR: 26.1-46.6], reflecting the heterogeneity of ALI/ARDS patients, and their response to PEEP, that complicates standard approaches to PEEP selection. All E _drs -Pressure curves have a clear inflection point before minimum E _drs , making PEEP selection straightforward. Model-based selected PEEP using the proposed metrics were higher than clinically selected values in 7/10 cases.

Conclusion

Continuous monitoring of the patient-specific E _lung and E _drs and minimally invasive PEEP titration provide a unique, patient-specific and physiologically relevant metric to optimize PEEP selection with minimal disruption of MV therapy.     

Prevention and correction with nonopiate analog of leu-enkephalin of disorders induced in the liver of newborn white rats by prenatal hypoxia]

The newborn rats after 48 hours after the birth were used in the study. The prenatal hypoxia caused the development of hypotrophy. Index of labeled 3H-thymidine nuclei decreased 1.5 fold, mitotic index decreased 1.4 fold. The content of aberrant figures of mitosis increased 2.6 times. Hexapeptide injection before hypoxia reduced the alterations caused by hypoxia, the data of body and liver weight did not differ from the control level.     

Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.