Effects of digoxin on diaphragmatic contractility in the piglet

Minute ventilation, arterial blood gases and pH, cardiac output, and transdiaphragmatic force generation were measured in eight anesthetized, tracheostomized piglets before and after administration of 40 micrograms/kg body wt of digoxin. No changes were noted in cardiac output, heart rate, tidal vol, respiratory rate, or minute ventilation. Blood pressure decreased from baseline to 60 min postinfusion. No change was noted in the force frequency curves at 30 and 60 min postinfusion. Serum digoxin levels averaged 10.4 ng/mL at 30 min and 5.6 ng/mL at 60 min. In seven control animals, no changes were noted in any ventilatory or hemodynamic parameter from baseline to 60 min. In contrast to the reported effects of digoxin on the diaphragm of adult humans and animals, digoxin did not augment diaphragmatic contractility in normal infant swine.     

Oxidative stress in preterm neonates at birth and on the seventh day of life

Previous studies have demonstrated increased oxidative damage to proteins and increased lipid peroxidation products in the plasma of hypoxic newborns at birth. We tested the hypothesis that hypoxic preterm newborns are at increased risk for oxidative stress in the first week of life. Heparinized blood samples of 34 hypoxic and 15 control preterm newborns were obtained at birth from the umbilical vein immediately after delivery and from a peripheral vein on postnatal d 7. Plasma levels of hypoxanthine, total hydroperoxide (TH), and advanced oxidation protein products (AOPP) were measured in cord blood and blood drawn on d 7. Hypoxanthine, TH, and AOPP levels were significantly higher in cord and d 7 blood samples of hypoxic newborn than control infants. Statistically significant correlations were observed between AOPP and hypoxanthine and between AOPP and TH plasma levels on d 7. AOPP and TH plasma levels significantly increased from cord to d 7 blood in neonates without hypoxia. These findings show that the oxidative stress observed in cord blood of hypoxic preterm newborns is still higher than control infants on d 7. The significant increase in TH and AOPP levels in nonhypoxic preterm newborns at the end of the first postnatal week indicates that damage caused by free radicals also occurs in nonhypoxic babies with normal clinical course. In summary, TH and AOPP production is prolonged for several days after birth in hypoxic preterm babies. The risk of free radical damage is lower but still exists in preterm neonates with normal clinical course.     

Effects of asphyxia on renal function in the newborn piglet

This investigation was undertaken to determine the nature of acute alterations in renal function following the production of hypoxemia, hypercarbia, and acidosis in newborn piglets 6-96 hr of age. After completion of the surgical procedure piglets were allowed to recover from the effects of anesthesia. When respiratory dead space was increased arterial oxygen tension decreased whereas arterial carbon dioxide tension and hydrogen ion concentration increased. There was little change in glomerular filtration rate. Total renal blood flow decreased and renal vascular resistance increased significantly (504 +/- 78 mm Hg/liter/mm/m2 to 1422 +/- 504). There was no change in distribution of intrarenal blood flow. Sodium excretion and urinary flow rate demonstrated significant parallel increases following the increase in dead space. Plasma renin concentration increased from 67 to 110 ng/ml.     

Effect of phenobarbital on cerebral blood flow in the newborn piglet under stress

Heart rate, cardiac output, mean arterial blood pressure (MABP), and cerebral blood flow (CBF) were measured in 12 newborn piglets (6 controls and 6 pretreated with 20 mg/kg phenobarbital), under two different stresses: pain stimulation and intravenous injection of 2.5 mg/kg phenylephrine. Phenobarbital prevented pain-induced tachycardia (p less than 0.05 versus controls) but failed to prevent hemodynamic changes induced by phenylephrine. CBF remained relatively constant throughout the study. A better correlation between cerebral vascular resistance and MABP was noted in the phenobarbital group (r = 0.58, p less than 0.01) than in the controls (r = 0.15, p = NS), suggesting that phenobarbital potentiates the vasoconstrictor effect of catecholamines.     

Relationship of birth weight to the pathogenesis of necrotizing enterocolitis in the neonatal piglet

The relationship between birth weight and the development of necrotizing enterocolitis (NEC) was studied in the term-delivered neonatal piglet. Hypoxia (pO2 less than 30% for 1 h) coupled with hyperviscosity (hematocrit more than 75%), with and without splenectomy, resulted in a high frequency and severity of NEC. This effect was most pronounced in low birth weight (LBW) animals. A statistically significant inverse relationship was found between birth weight and the number and severity of lesions. Splenectomy increased the incidence and severity of lesions particularly in LBW animals. A predominance of lesions was found in the distal ileum with occasional occurrences elsewhere in the small bowel and in the proximal colon. The neonatal piglet is capable of producing the full spectrum of NEC under acceptable experimental conditions. LBW is a significant predisposing factor in the pathogenesis of NEC.     

Effects of antenatal glucocorticoids on circulatory adaptation at birth in the ovine fetus

OBJECTIVE: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO2, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. STUDY DESIGN: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (<10%) and then with high (100%) FiO2 in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. RESULTS: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO2, mean PVR decreased by 40% in the control group (from 0.44 +/- 0.01 to 0.25 +/- 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 +/- 0.02 to 0.19 +/- 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O2, there was no difference in PVR decrease between groups (0.15 +/- 0.02 mm Hg/ml/min in the GC group vs. 0.14 +/- 0.01 mm Hg/ml/min in the control group). CONCLUSION: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O2. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.     

The influence of piglet birth weight on physical and behavioural development in early life

The objective of this study was to determine whether body weight at birth influences the physical and behavioural development of the neonatal pig. Sixteen sows and their litters were randomly allocated into four treatment groups. From the normal distribution curve of their birth weight, piglets were sub-divided into three groups: (1) low (<10th percentile) (2) normal (10-90th percentile) and (3) high (>90th percentile).To assess behavioural development, each litter was exposed to a ball placed in the creep area for a period of 1,800 s, and evaluated once over a 3-day period starting on either 5, 7, 14 or 21 days of postnatal life. Their response to, and interaction with, an object was used to calculate a numerical index of piglet behavioural development. Teat order was calculated following observations during consecutive suckling on days 11, 13 and 15 of life, and dominance hierarchy was assessed on day 12, 14 and 16. Individual body weight was recorded on days 0, 5, 7, 14 and 21 of postnatal life. Statistical differences between groups were analysed using general linear model, analysis of variance. Regression analyses were used to determine relationships between physical and behavioural development with teat order and dominance. There was a significant (p < 0.001) relationship between birth weight, growth performance and behavioural development. Behavioural developmental index (BDI) significantly improved (p < 0.001) with age and was also influenced by the day on which the ball was introduced (p < 0.01). Body weight on day 1 of the test was significantly (p < 0.001) correlated to BDI and age at test. Piglets demonstrating compensatory growth were more dominant and exhibited an improved behavioural developmental score than their slower growing littermates. In conclusion, compromised growth in utero can have a detrimental effect on the physical and behavioural development of the neonate. Animals with an enhanced developmental index in conjunction with a higher dominance value exhibited a improved neonatal growth performance.     

Effects of altitude versus economic status on birth weight and body shape at birth

The compelling evidence linking small size at birth with later cardiovascular disease has renewed and amplified a clinical and scientific interest in the determinants of fetal growth. Although the effects of maternal nutrition on fetal growth have been extensively studied, comparatively little is known about the effects of maternofetal hypoxia. This study tested the hypothesis that in highland regions, high altitude rather than maternal economic status is associated with reduced and altered fetal growth by investigating the effects of high altitude versus economic status on birth weight and body shape at birth in Bolivia. Bolivia is geographically and socioeconomically unique. It contains several highland (>3500 m above sea level) and lowland (<500 m) cities that are inhabited by very economically divergent populations. Birth weight, body length, and head circumference were compared between a high- (n = 100) and low- (n = 100) income region of La Paz (3649 m; largest high-altitude city) and a high- (n = 100) and low- (n = 100) income region of Santa Cruz (437 m; largest low-altitude city). In addition, the frequency distribution across the continuum of birth weights was plotted for babies born from high- and low-income families in La Paz and Santa Cruz. Mean birth weights were lower in babies from La Paz than in babies from Santa Cruz in both high- and low-income groups. The cumulative frequency curve across all compiled birth weights was shifted to the left in babies from La Paz compared with those from Santa Cruz, regardless of economic status. The frequency of low birth weight (<2500 g) was higher in babies from La Paz than from Santa Cruz in both high- and low-income groups. In addition, at high altitude but not at low altitude, high income was associated with an increase in the head circumference:birth weight ratio. These findings suggest that high altitude rather than economic status is associated with low birth weight and altered body shape at birth in babies from Bolivia.     

Nonprotein-bound iron and plasma protein oxidative stress at birth

We previously reported plasma nonprotein-bound iron (NPBI) as a reliable early indicator of intrauterine oxidative stress (OS) and brain injury. We tested the hypothesis that albumin, an NPBI serum carrier, is the major target of NPBI-induced OS. Twenty-four babies were randomly selected from 384 newborns constituting the final cohort of a prospective study undertaken to evaluate the predictive role of NPBI in cord blood for neurodevelopmental outcome. Twelve were selected in the group with lowest NPBI levels (0-1.16 microM) and good neurodevelopmental outcome and 12 in the group with highest NPBI levels (>or=15.2 microM) and poor neurodevelopmental outcome. Protein carbonyl groups were identified in cord blood samples by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and Western blotting with anti-2,4-dinitrophenyl (DNP) antibodies. Two series of immunoreactive spots, corresponding to serum albumin and alpha-fetoprotein, were found only in the group with highest NPBI levels. We found an association between NPBI and carbonylated proteins in babies with highest NPBI levels. Since NPBI may produce hydroxyl radicals through the Fenton reaction, the major target of OS induced by NPBI is its carrier: albumin. Oxidation of albumin can be expected to decrease plasma antioxidant defenses and increase the likelihood of tissue damage due to OS in the newborns.     

IGF-related proteins at birth in a case of antenatally diagnosed Silver-Russell syndrome

We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of Silver-Russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.     

Activin a plasma levels at birth: an index of fetal hypoxia in preterm newborn

Activin-A is a growth factor involved in cell growth and differentiation, neuronal survival, early embryonic development and erythropoiesis. Hypoxemia is a specific trigger for increasing activin-A in fetal lamb circulation. We tested the hypothesis that fetal hypoxia induces activin-A secretion in preterm newborn infants. Fifty newborn infants with gestational ages ranging from 26 to 36 wk were enrolled in a prospective study performed at the Pediatrics, Obstetrics and Reproductive Medicine Department, University of Siena, Italy. Heparinized blood samples were obtained from the umbilical vein after cord clamping, immediately after delivery. Activin A, hypoxanthine (Hx), xanthine (Xa) plasma levels and absolute nucleated red blood cell (NRBC) count were measured. Activin-A levels (p < 0.0001) and NRBC (p < 0.0001) were significantly higher in hypoxic than in non hypoxic preterm newborns. Cord activin A levels were significantly related with Hx (taua=0.64, taub=0.64, p < 0.0001) and Xa (taua=0.56, taub=0.57, p < 0.0001) levels, NRBC ((taua=-0.45, taub=-0.46, p < 0.0001) count; pH (taua=-0.47, taub=-0.48, p < 0.0001) and base deficit (taua=-0.36, taub=0.-0.36, p = 0.0002). Preterm newborns with signs of perinatal hypoxia at birth have increased activin-A levels, suggesting that activin-A may reflect indirectly intrauterine hypoxia.     

Intestinal ischemic injury following mild hypothermic stress in the neonatal piglet

The core body temperature of unanesthetized neonatal piglets was lowered 4 +/- 1 degrees C for 4.5 h. Although systolic blood pressure, arterial blood gases, and pH were similar in hypothermic and control animals, grossly evident small intestinal injury occurred in 94% of hypothermic piglets but in none of the controls (p less than 0.01). The histopathology of the intestinal lesions in the experimental animals was characteristic of ischemic injury and ranged from superficial mucosal necrosis to transmural infarct. The lesions were more frequent in the mid- and distal small bowel and involved the muscularis propria only in the distal small bowel. The location and histopathologic characteristics of the bowel lesions in these animals support the concept that mild hypothermia could be a pathogenetic factor in the ischemic bowel lesions of human neonatal necrotizing enterocolitis.     

Developmental sensitivity of the piglet brain to docosahexanoic acid.

Human formula-fed infants have a lower concentration of docosahexanoic acid (DHA) in cerebral cortex compared with breast-fed infants. It is uncertain whether this biochemical deficit is reversible in later infancy. We used a piglet model to determine whether a critical window exists for the deposition of DHA in cerebral cortex during early postnatal development. Milk formula supplemented with DHA was fed to piglets for one of two 14-day periods commencing at either 2 or 16 d of life (early or late supplementation). Comparison of cortical DHA levels in response to supplemented formula was made with age-matched piglets receiving a control formula devoid of DHA. The level of DHA incorporated into whole brain during supplemented formula-feeding seemed to be less with increasing postnatal age. However, when cerebral cortex was examined, dietary DHA was efficiently incorporated during both early and late supplementation periods. Thus, analysis of whole brain was misleading, emphasizing the need to consider the effect of myelination when interpreting developmental changes in brain fatty acids. We conclude that the piglet cerebral cortex is responsive to dietary DHA during the postnatal phase of the brain growth spurt. The lower cortical DHA levels of human formula-fed infants may, therefore, be reversible in later infancy. Plasma phospholipid DHA levels were approximately doubled and liver phospholipid DHA levels increased 50% relative to starting values during control formula-feeding. This suggests a higher rate of DHA synthesis in the piglet in comparison with the human infant, which may be an important limitation of the piglet model.     

Effects of anemia and growth retardation on respiratory activity in the piglet

Respiratory activity (RA) was assessed in a piglet model by giving chloralose (Ch), 6 mg/kg i.v. every 2 min, until the appearance of apnea. The total cumulative dose of Ch (mg/kg) which produced permanent apnea (lethal dose, LD) was determined. The slope of the dose-respiratory frequency curve (R = ae-lambda Ch) was also computed. The LD of Ch increased progressively with age, while respiratory frequency (lambda) decreased. However, in piglets with severe spontaneous anemia (hematocrit less than 10%), the LD of Ch was less than half that expected for the age groups, and the rate of reduction of gamma was much greater. The enhanced sensitivity to inhibition of RA may relate in part to anemia with reduced O2-carrying capacity to the CNS, and in part to growth retardation with delayed respiratory center maturation.     

新生猪不同程度脑缺氧与脑功能、脑损伤关系的近红外光谱研究

目的通过检测不同程度缺氧时新生猪脑氧合的变化,研究脑缺氧程度-脑功能-脑损伤之间的规律。方法对15只新生猪检测脑组织血氧饱和度（Regional oxygen saturation,rSO2）,给新生猪机械通气吸入低浓度氧,造成脑rSO2不同进行分组。实验过程监测生理参数、脑电,脑损伤后72h进行海马CAl区光镜及电镜检查。结果在缺氧至脑rSO2〉40％的小猪组,缺氧后平均动脉压（Mean arterial pressure,MAP）为（56±0.00）mmHg（1 mm Hg=0.133 kPa）。血乳酸（2.3±1.2）mmol／L,脑电变化不明显,脑组织光镜、电镜无明显改变。在缺氧至脑rSO2 30％～40％时,MAP为（734±8）mmHg,血乳酸增高至（8.2±3.9）mmol／L,脑电观察的脑功能发生改变,但缺氧后有所恢复,脑组织光镜有缺血性改变,电镜表现为海马CAl区神经元线粒体损伤。当缺氧至脑rSO2〈30％时,MAP为（35±0.00）mmHg,血乳酸增高至（12±2）mmol／L,脑电观察脑功能受损,部分在缺氧后难以恢复,光镜下细胞有空泡形成,破碎,海马CAl区神经元线粒体严重损伤。结论在不同程度的缺氧下,当脑至rSO2 30％～40％时,新生猪出现脑损伤,当rSO2〈30％,出现严重的脑损伤;rSO2越低,脑功能、脑损害越重;无创近红外光谱检测到的脑组织rSO2可以在脑缺氧过程中反映脑损伤及损伤的程度。     

Neuro-ultrasonography in the assessment of perinatal lesions of the brain in high-risk children at birth and at 3 months of age

As many as 135 children belonging to the group at high risk underwent neurosonography to assess the neuropsychic status in the early neonatal period and at an age of three months. A high rate of perinatal brain injuries was established as was a close relationship between the gestation age of the child, on the one hand and the character and intensity of the injury, on the other one. It has been revealed that the combination of deep immaturity and severe ante-intranatal hypoxia predetermines almost 100% injury of the brain structures, bringing about the formation of organic pathology and impairment of the psychoneurologic development of these children by the age of 3 months.