Preterm Pups Research Articles

Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model

BackgroundSupplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)–associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. Materials and methodsPre- and full-term newborn Sprague–Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal–Wallis and Mann–Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. ResultsLevels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. ConclusionsProinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade.

IMAGING LUNG AERATION AND LUNG LIQUID CLEARANCE AT BIRTH USING PHASE CONTRAST X‐RAY IMAGING

The transition to extra-uterine life at birth is critically dependent on airway liquid clearance to allow the entry of air and the onset of gaseous ventilation. We have used phase contrast X-ray imaging to identify factors that regulate lung aeration at birth in spontaneously breathing term and mechanically ventilated preterm rabbit pups. Phase contrast X-ray imaging exploits the difference in refractive index between air and water to enhance image contrast, enabling the smallest air-filled structures of the lung (alveoli; < 100 microm) to be resolved. Using this technique, the lungs become visible as they aerate, allowing the air-liquid interface to be observed as it moves distally during lung aeration. Spontaneously breathing term rabbit pups rapidly aerate their lungs, with most fully recruiting their functional residual capacity (FRC) within the first few breaths. The increase in FRC occurs mainly during individual breaths, demonstrating that airway liquid clearance and lung aeration is closely associated with inspiration. We suggest that transpulmonary pressures generated by inspiration provide a hydrostatic pressure gradient for the movement of water out of the airways and into the surrounding lung tissue after birth. In mechanically ventilated preterm pups, lung aeration is closely associated with lung inflation and a positive end-expiratory pressure is required to generate and maintain FRC after birth. In summary, phase contrast X-ray imaging can image the air-filled lung with high temporal and spatial resolution and is ideal for identifying factors that regulate lung aeration at birth in both spontaneously breathing term and mechanically ventilated preterm neonates.

Role of Secretoglobin 3A2 in Lung Development

Secretoglobin 3A2 (SCGB3A2) was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at Embryonic Day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphologic changes, suggesting that SCGB3A2 may be involved in lung development in addition to a known role in lung inflammation. To determine whether SCGB3A2 plays a role in lung development. To assess a potential role for SCGB3A2 during early lung development, wild-type and Nkx2-1-null fetal lungs of early developmental stages were subjected to ex vivo organ culture in the presence of SCGB3A2. Nkx2-1-null fetuses were exposed to SCGB3A2 during early organogenesis period through intravenous administration of this protein to Nkx2-1-heterozygous pregnant females carrying these null fetuses. Cultured lungs and fetal lungs were subjected to histologic and immunohistochemical analyses. To assess a role for SCGB3A2 in late lung development, SCGB3A2 was administered to pregnant wild-type females during mid- to late organogenesis stages, and the preterm pups and/or their lungs were evaluated for extent of maturity using breathing motion, gross morphology and histology of lungs, expression of gestational stage-specific genes, and phospholipid profiles. SCGB3A2 significantly promoted both early and late stages of lung development. SCGB3A2 is a novel growth factor in lung.

Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs

Objectives: Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs. Study Design: 112 fetuses from 21 time-mated, pregnant, giant white rabbits received maternal injections of BM at either 0.05 or 0.1 mg/kg/day on days 25–26 of gestational age. Controls received either saline (10 does, 56 fetuses) or no injection (10 does, 59 fetuses). Fetuses were harvested from day 27 onwards until term (day 31). 44 additional fetuses (8 does) were harvested between days 23 and 26. Endpoints were wet lung-to-body weight ratio, vascular morphometric indices and immunohistochemistry staining for α-smooth muscle actin, Flk-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). ANOVA (Tukey’s test) and independent t test (p < 0.05) were used for comparison between BM and saline groups. Results: Maternal BM injected on days 25–26 to pregnant rabbits induced a significant decrease in fetal body and lung weight and the lung-to-body weight ratio in the preterm pups shortly after injection. BM led to a dose-dependent thinning of the arterial media and adventitia (pulmonary arteries with an external diameter (ED) of <100 µm), to an increase in the percentage of non-muscularized peripheral vessels (ED <60 µm), in eNOS and VEGF immunoreactivity of the endothelial and smooth muscle cells in the pulmonary vessels and to an increase in Flk-1-positive pulmonary epithelial cell density. Conclusions: Maternal administration of BM caused thinning of the arterial wall of pulmonary vessels (ED <100 µm) and a decrease in muscularization in peripheral vessels (ED <60 µm). This coincided with increased expression of Flk-1 in the endothelium and smooth muscle cells of the pulmonary arteries. All the effects studied were dose-dependent.

Proximal arterial vasoconstriction precedes regression of the hyaloid vasculature

Purpose. To determine whether constriction of proximal arterial vessels precedes involution of the distal hyaloid vasculature in the mouse, under normal conditions, and whether this vasoconstriction is less pronounced when the distal hyaloid network persists, as it does in oxygen-induced retinopathy (OIR). Methods. Photomicrographs of the vasa hyaloidea propria were analysed from pre-term pups (1–2 days prior to birth), and on Days 1–11 post-birth. The OIR model involved exposing pups to ~90% O 2 from D1–5, followed by return to ambient air. At sampling times pups were anaesthetised and perfused with india ink. Retinal flatmounts were also incubated with FITC-lectin (BS-1, G. simplicifolia,); this labels all vessels, allowing identification of vessels not patent to the perfusate. Results. Mean diameter of proximal hyaloid vessels in pre-term pups was 25.44 ± 1.98 µm; ± 1 SEM). Within 3–12 hrs of birth, significant vasoconstriction was evident (diameter:12.45 ± 0.88 µm), and normal hyaloid regression subsequently occurred. Similar vasoconstriction occurred in the O 2 -treated group, but this was reversed upon return to room air, with significant dilation of proximal vessels by D7 (diameter: 31.75 ± 11.99 µm) and distal hyaloid vessels subsequently became enlarged and tortuous. Conclusions. Under normal conditions, vasoconstriction of proximal hyaloid vessels occurs at birth, preceding attenuation of distal hyaloid vessels. Vasoconstriction also occurs in O 2 -treated pups during treatment, but upon return to room air, the remaining hyaloid vessels dilate proximally, and the distal vessels become dilated and tortuous. These observations support the contention that regression of the hyaloid network is dependent, in the first instance, on proximal arterial vasoconstriction.

Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: A new rat model of pulmonary fibrosis (bronchopulmonary dysplasia)

Objective: To evaluate the postnatal effects of prenatal dexamethasone treatment of preterm rats and to test the hypothesis that prenatal dexamethasone treatment protects against pulmonary oxygen toxicity in the preterm rats and stimulates lung antioxidant enzyme levels in response to hyperoxia. Study design: We administered dexamethasone (0.4 mg/kg, intraperitoneally), or equivolume saline solution to pregnant rats at 48 and 24 hours before premature delivery at gestation day 21. Both groups of prematurely delivered rat pups were randomly assigned to either >95% O 2 or room air immediately after birth and brief resuscitation. Results: The hyperoxic survival rates from day 1 through day 14 were similar in both dexamethasone-treated and control preterm O 2 groups. At 7 days of hyperoxia, the preterm pups demonstrated similar lung antioxidant enzyme activity and surfactant content responses to high O 2 in the dexamethasone-treated and control groups. Lung quantitative morphometry changes were similar (equal degree of inhibition of normal alveolar development) in both groups. Unexpectedly, the lungs of the preterm O 2 control rats showed evidence of septal fibrosis and the pups that received dexamethasone-O 2 showed even greater severity of septal fibrosis and a greater increase (+50%) of lung hydroxyproline compared with the O 2 group control rats. Conclusions: In preterm animals, prenatal dexamethasone administration does not show any of the hypothesized protective effects against hyperoxia or protective biochemical lung changes during prolonged O 2 exposure. However, prenatal dexamethasone administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to bronchopulmonary dysplasia. (J Pediatr 1997;130:409-16)

PRENATAL DEXAMETHASONE (DEX) ADMINISTRATION TO PREMATURE RATS EXPOSED TO PROLONGED HYPEROXIA: A NEW RAT MODEL OF PULMONARY FIBROSIS[BRONCHOPULMONARY DYSPLASIA (BPD)]. † 1953

Although prenatal DEX treatment is known to improve hyperoxic survival in term newborn rats and to stimulate the responses of the lung antioxidant enzyme (AOE) system to hyperoxia, little is know about the postnatal effects of prenatal DEX on prolonged exposure to hyperoxia in preterm animals. To examine the hypothesis that prenatal DEX treatment would also show protective effects in preterm rats exposed to hyperoxia, we administered DEX(0.4 mg/kg, i.p.), or equivolume saline to pregnant rats at 48 and 24 h prior to premature delivery at gestation d 21 (term=22 d). Both groups of preterm rat pups were randomized to either >95% O2 or room air immediately after birth. The hyperoxic survival rates from d 1 through d 14 turned out to be similar in both DEX- and control-O2 groups. At 7 d of hyperoxia, the preterm pups demonstrated similarly increased lung AOE activity and surfactant content responses to high O2 in the DEX and control groups. Lung quantitative morphometry was changed similarly (equal degree of inhibition of normal alveolar development) in both O2 groups. Unexpectedly, the lungs of preterm control-O2 pups showed evidence of septal fibrosis at 13-14 d in O2, and the DEX-O2 group showed even much greater severity of septal fibrosis and a greater increase of lung hydroxyproline compared with the O2 controls. We conclude that in preterm animals, prenatal DEX administration does not show any of the hypothesized protective effects during prolonged O2 exposure. However, prenatal DEX administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to BPD. This preterm rat model is a much more practical experimental model than the earlier excellent (but very expensive) baboon/monkey model of BPD. Table

Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig: Effects on pulmonary inflammation and antioxidant status

Dexamethasone ( 10mg kg day ) or vehicle was administered in a randomized, controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% 0 2. Dexamethasone treatment reduced the growth rate of pups, the effect occurring earlier (0–3 days) in 21% 0 2-treated pups than in 95% 0 2-treated pups (5–7 days). Exposure to 95% O 2 reduced the survival rate of preterm animals (73% vs 100%. P < 0.05). Surviving pups developed acute lung injury, characterized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (16.4 × 10 4 vs 9.4 × 10 4 mL ; P < 0.05) and following return to ambient conditions (28.0 × 10 4 vs 5.1 × 10 4 mL : P < 0.05). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities ( Cu Zn -superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxiaexposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.

Distribution of vitamin e between tissues during periods of hyperoxic and nutritional stress in the preterm guinea pig

1. 1. Using a preterm guinea pig model we examined the impact of oxidative and nutritional stress on the vitamin E status of a number of immature tissues. 2. 2. Liver, brain, lung, red blood cell and plasma α-tocopherol concentrations were measured in fed and fasted, preterm guinea pigs exposed to 21 or 95% oxygen for 48 hr. 3. 3. Exposure to hyperoxia did not influence plasma, red blood cell, lung or brain vitamin E status of preterm pups. Liver a-tocopherol content was reduced 20% following 48 hr hyperoxic exposure ( P < 0.05). 4. 4. Food restriction (48 hr) alone reduced liver (41%) and red blood cell (32%) a-tocopherol concentrations in preterm animals while plasma, lung and brain vitamin E levels were unaffected. Combined with hyperoxic exposure, food restriction resulted in a (50%) fall in liver a-tocopherol concentration ( P < 0.01). 5. 5. The findings of this study suggest that the liver acts as a reservoir for vitamin E in the perinatal period, releasing increased quantities of this lipid soluble antioxidant for use by non-hepatic tissues during periods of hyperoxic and nutrient stress.

Differing Response of the Glutathione System to Fasting in Neonatal and Adult Guinea Pigs

Abstract Adult, term neonatal and 3 day preterm neonatal guinea pigs were fasted for 48 hr, and the glutathione concentrations of the liver and lung assessed. In adult animals, glutathione concentration decreased by 43% in the liver and 29% in the lung with respect to fed controls. The decrease in liver glutathione was associated with a 75% reduction in the hepatic activity of τ-glutamyltranspeptidase (τGGT). Conversely, both liver and lung glutathione levels in preterm pups remained unchanged following 48 hr food restriction. Likewise, hepatic τGGT, glutathione reductase (GRed) and glutathione peroxidase (GPx) activities were unchanged by fasting in preterm pups. Fasting increased pulmonary GPx activity by 27% in these pups. In fasted, term animals, substantial increases in both lung (65%) and liver (80%) glutathione concentrations were observed, with concomitant increases in GPx and GRed activities. Hepatic τGGT activity was significantly reduced (57%) in term pups. These results may suggest that the neonatal guinea pig can maintain tissue glutathione status during periods of nutrient stress, through an increased capacity for recycling oxidized glutathione and a decrease in turnover of the tripeptide. Guinea pig neonates are therefore able to resist starvation-induced decreases in tissue glutathione levels seen in adult rodents. If this is a general neonatal response it may have important clinical implications in the treatment of preterm babies.

Effects of pentoxifylline on in vivo leukocyte function and clearance of group B streptococci from preterm rabbit lungs

Pentoxifylline was evaluated for its ability to enhance inactivation of group B streptococci in lungs of prematurely born rabbits. Mechanisms associated with intrapulmonary streptococcal clearance and the pharmacodynamics of pentoxifylline were also investigated. Randomized, controlled animal trial. University research laboratory. A total of 123 New Zealand rabbits were delivered prematurely by cesarean section and were used for clearance studies. Twenty-three preterm pups were additionally utilized to study the pharmacodynamics of pentoxifylline. Preterm rabbits were infected with group B streptococcal aerosols and given intraperitoneal injections of either pentoxifylline (25, 12.5, and 12.5 mg/kg) or placebo at 0, 6, and 12 hrs after infection. At 0, 4, and 24 hrs, the numbers of streptococci were determined in the left lung, while the right lung underwent bronchoalveolar lavage to quantify intra-alveolar leukocytes, phagocytosis of inhaled bacteria, and concentrations of lysozyme and tumor necrosis factor. In a separate experiment, blood and bronchoalveolar fluid from infected animals were analyzed for pentoxifylline content. Streptococcal proliferation was less in pentoxifylline-treated animals than in controls at 24 hrs (p < .01). Pulmonary macrophages and polymorphonuclear leukocytes recovered from bronchoalveolar lavage fluid did not differ in numbers or phagocytic activity. Pentoxifylline-treated animals had lower levels of lysozyme (p < .02) and tumor necrosis factor (p < .005) in bronchoalveolar lavage fluid compared with placebo-treated pups. Therapeutic levels of pentoxifylline were achieved in blood and bronchoalveolar lavage fluid. Despite lowering lysozyme and tumor necrosis factor content in epithelial lining fluid, pentoxifylline improves the inactivation of group B streptococci in preterm rabbit lungs. These findings suggest that increased group B streptococcal clearance was coincident with an anti-inflammatory effect due to pentoxifylline. We conclude pentoxifylline may be clinically useful as an adjunctive therapy for group B streptococcal pneumonia in newborns.

Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration.

Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.

Differing response of the glutathione system to fasting in neonatal and adult guinea pigs

Adult, term neonatal and 3 day preterm neonatal guinea pigs were fasted for 48 hr, and the glutathione concentrations of the liver and lung assessed. In adult animals, glutathione concentration decreased by 43% in the liver and 29% in the lung with respect to fed controls. The decrease in liver glutathione was associated with a 75% reduction in the hepatic activity of τ-glutamyltranspeptidase (τGGT). Conversely, both liver and lung glutathione levels in preterm pups remained unchanged following 48 hr food restriction. Likewise, hepatic τGGT, glutathione reductase (GRed) and glutathione peroxidase (GPx) activities were unchanged by fasting in preterm pups. Fasting increased pulmonary GPx activity by 27% in these pups. In fasted, term animals, substantial increases in both lung (65%) and liver (80%) glutathione concentrations were observed, with concomitant increases in GPx and GRed activities. Hepatic τGGT activity was significantly reduced (57%) in term pups. These results may suggest that the neonatal guinea pig can maintain tissue glutathione status during periods of nutrient stress, through an increased capacity for recycling oxidized glutathione and a decrease in turnover of the tripeptide. Guinea pig neonates are therefore able to resist starvation-induced decreases in tissue glutathione levels seen in adult rodents. If this is a general neonatal response it may have important clinical implications in the treatment of preterm babies.

Effect of food restriction on hyperoxia-induced lung injury in preterm guinea pig.

Undernutrition may exacerbate hyperoxia-induced lung injury, a finding that may be of significance in the early clinical management of the premature human infant. Addressing this specific problem, we found that 72 h of food restriction in guinea pig pups delivered 3 days preterm increased mortality rates among pups exposed to 95% oxygen (8/18) and yet had no effect on 21% oxygen (air)-exposed pups (0/10). Reduced tolerance of hyperoxic conditions was not, however, associated with increased lung injury, assessed as pulmonary microvascular leakage. Pulmonary antioxidant enzyme activities [Cu,Zn superoxide dismutase (SOD), Mn SOD, glutathione peroxidase, and catalase] were unaltered by starvation or hyperoxia. Lung glutathione concentration was slightly decreased after food restriction, whereas hyperoxic exposure did not change either lung or bronchoalveolar lavage fluid glutathione concentrations or lung antioxidant enzyme activities. Increased susceptibility to the lethal effects of oxygen in the starved preterm guinea pig pup could not be attributed to a deficiency of pulmonary antioxidant defenses.

The pre-term guinea-pig: a model for the study of neonatal lung disease.

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P less than 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in pre-term pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in pre-term pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex.(ABSTRACT TRUNCATED AT 250 WORDS)

The preterm rat: a model for studies of acute and chronic neonatal lung disease.

A preterm rat model has been developed for studies of acute and chronic neonatal lung disease. Premature delivery 24 h before the normal time of delivery is associated with immature pulmonary phospholipid and antioxidant enzyme profiles. The premature lung is more fragile and ruptures at a lower lung vol (172 +/- 8 microL) than the full-term fetal lung (259 +/- 14 microL). Only 7% of premature lungs will float in liquid, after inflation to 85% of the rupture vol, compared with 87% of term fetal lungs. This lung immaturity was reflected in a survival rate of only 6% by 36 h after delivery if the preterm pups were placed in air, which increased to 47% when they were placed in greater than 95% oxygen. Though greater than 95% oxygen enhanced survival of preterm pups during the 1st wk of life, these survivors had a 50% mortality during the 2nd wk of exposure to greater than 95% oxygen. The preterm pup will tolerate intraperitoneal injection of antioxidant enzymes entrapped in liposomes and has a better retention of these liposomes in the lung compared with the term pup. We conclude that the preterm rat is a suitable model for studies of acute and chronic neonatal lung disease.

Influences of the early olfactory environment on the survival, behavior and pituitary-adrenal activity of caesarean delivered preterm rat pups.

In a first experiment, vaginally delivered Day 21 and Caesarean delivered Day 20 and Day 21 rat pups were isolated in the presence of various odorants or no odorant for 1 hr immediately following birth. For Day 20 pups, exposure to novel mint odor resulted in higher mortality during isolation than did exposure to the odor of amnion/placenta. In the preterm pups, whole body corticosterone levels were higher in all isolation treatments than they were immediately following birth. For Day 21 pups, isolation treatments had no effect on corticosterone concentrations, but overall, corticosterone levels were higher following Caesarean section than they were following vaginal delivery. A second experiment replicated the mint odor-induced increase in mortality and revealed a lower activity level in preterm pups exposed to mint odor than in those exposed to the odor of amnion/placenta. Mechanical movement of the pups during exposure eliminated the effects of mint odor on mortality and activity. There was a positive correlation between corticosterone concentrations and pup activity during isolation. These results demonstrate potent influences of seemingly minor changes in early sensory stimulation on the preterm pup. The paradigm might provide a useful animal model for studying the effects of variations in ambient stimulation on premature infants.

Gastrointestinal growth in preterm and full-term rat pups

Gastrointestinal growth in preterm and full-term rat pups