Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

Several factors are associated with bronchopulmonary dysplasia. Among them, hyperoxia and lung immaturity are considered to be fundamental; however, the effect of malnutrition is unknown. Our objective was to evaluate the effects of 7 days of postnatal malnutrition and hyperoxia on lung weight, volume, water content, and pulmonary morphometry of premature rabbits. After c-section, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O2 (MH, N = 18). Malnutrition was defined as a 30% reduction of all the nutrients provided in the control diet. Treatments were maintained for 7 days, after which histological and morphometric analyses were conducted. Lung slices were stained with hematoxylin-eosin, modified orcein-resorcin or picrosirius. The results of morphometric analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 ± 0.19; CH: 0.96 ± 0.28; MA: 0.65 ± 0.17; MH: 0.79 ± 0.22 g) and water content, as well as the number of alveoli (CA: 12.43 ± 3.07; CH: 8.85 ± 1.46; MA: 7.33 ± 0.88; MH: 6.36 ± 1.53 x 10-3/mm) and elastic and collagen fibers. Hyperoxia reduced the number of alveoli and increased septal thickening and the mean linear intercept. The reduction of alveolar number, collagen and elastic fibers was intensified when malnutrition and hyperoxia were associated. These data suggest that dietary restriction enhances the magnitude of hyperoxia-induced alveolar growth arrest and lung parenchymal remodeling. It is interesting to consider the important influence of postnatal nutrition upon lung development and bronchopulmonary dysplasia.FAPES

Respostas pulmonares à restrição nutricional e à hiperoxia em coelhos prematuros Pulmonary responses to nutritional restriction and hyperoxia in premature rabbits

OBJETIVOS: Este modelo experimental foi desenvolvido para analisar os efeitos da restrição nutricional e da hiperoxia, durante 11 dias, sobre o peso e a morfometria pulmonares, em coelhos prematuros. MÉTODOS: Após cesárea, coelhos New Zealand White com idade gestacional de 28 dias foram randomizados nos seguintes grupos: dieta controle e ar ambiente, dieta controle e hiperoxia (> 95% O2), restrição nutricional e ar ambiente e restrição nutricional e hiperoxia (>95% O2). A restrição nutricional foi obtida com uma redução em 30% de todos os nutrientes da dieta controle. As lâminas de pulmão foram coradas com hematoxilina-eosina, resorcina-orceína modificada e picrosírius, sendo posteriormente realizada a análise morfométrica RESULTADOS: Observou-se um menor ganho de peso no grupo restrição nutricional e hiperoxia (p < 0,001) a partir do quarto dia e, no grupo restrição nutricional e ar ambiente (p < 0,001), a partir do sexto dia de vida, em relação aos respectivos grupos controles. A restrição nutricional reduziu o número de alvéolos (p < 0,001) e o depósito de colágeno (p < 0,001). A hiperoxia produziu uma redução do número de alvéolos (p < 0,001) e do depósito de colágeno (p < 0,001), além de maiores intercepto linear médio (p < 0,05) e espessamento de septos inter-alveolares (p < 0,001). A restrição nutricional associada à hiperoxia intensificou a redução do número de alvéolos (p < 0,001) e do depósito de colágeno (p < 0,001). CONCLUSÕES: A restrição nutricional intensificou as alterações morfométricas pulmonares produzidas pela hiperoxia, especialmente em relação à alveolização e depósito de colágeno.<br>OBJECTIVES: To analyze the effects of nutritional restriction and hyperoxia on lung weight and pulmonary morphometry in premature rabbits during the first 11 days of life METHODS: New Zealand White rabbits were delivered by C-section at 28 days' gestational age and randomized into four groups: control diet and room air, control diet and hyperoxia (> 95% O2), nutritional restriction and room air and nutritional restriction and hyperoxia (> 95% O2). Nutritional restriction was achieved by reducing all nutrients by 30% in comparison with the control diet. Lung tissue slides were stained with hematoxylin-eosin, modified resorcin-orcein and picrosirius, before morphometric analysis was performed. RESULTS: From the fourth day onwards, less weight was gained by the nutritional restriction and hyperoxia group (p < 0.001) and from the sixth day on, by the nutritional restriction and room air group (p < 0.001), in comparison with their respective control groups. Nutritional restriction decreased alveoli number (p < 0.001) and collagen deposition (p < 0.001). Hyperoxia was responsible for reductions in number of alveoli (p < 0.001) and collagen deposition (p < 0.001), in addition to higher mean linear intercept values (p < 0.05) and thickening of alveolar septa (p < 0.001). When nutritional restriction was associated with hyperoxia, the reductions in number of alveoli (p < 0.001) and of collagen deposition (p < 0.001) intensified. CONCLUSIONS: Nutritional restriction intensified the changes of pulmonary architecture findings caused by hyperoxia, in particular through alterations to alveolarization and collagen deposition

Pulmonary emphysema induced by passive smoking: an experimental study in rats

We describe a short time model for inducing experimental emphysema in rats by chronic tobacco smoke inhalation. Three groups of male Wistar rats (6 months old) were studied: controls (N = 8), rats intoxicated for 45 days (s-45, N = 7) or for 90 days (s-90, N = 8). The exposed animals were intoxicated 3 times a day (10 cigarettes per exposure period), 5 days a week. Pulmonary damage was assessed by means of functional tests and quantitative pathological examination of the airways and lung parenchyma. The s-45 and s-90 animals were similar in terms of functional residual capacity (FRC) corrected for body weight (FRC/kg) but both groups of smoking rats exhibited significantly higher FRC/kg values than the controls (s-45 = 6.33; s-90 = 6.46; controls = 3.78; P&lt;0.05). When the two groups of smoking rats were pooled together and compared to controls, they showed decreased lung elastance (1.6 vs 2.19; P = 0.046) and increased mean linear intercept (Lm) (85.14 vs 66.44; P = 0.025). The s-90 animals presented higher inflammation and muscular hypertrophy at the level of the axial bronchus than the controls (P&lt;0.05). When smoking groups were pooled and compared to controls, they presented significantly higher inflammation at the lateral level (P = 0.028), as well as airway secretory hyperplasia (P = 0.024) and smooth muscle hypertrophy (P = 0.005) at the axial level. Due to its simplicity, low cost and short duration, this technique may be a useful model to obtain new information about airspace remodeling due to chronic tobacco consumptio

Inducible Nitric Oxide Synthase Inhibition Attenuates Physical Stress-Induced Lung Hyper-Responsiveness and Oxidative Stress in Animals with Lung Inflammation

Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2 alpha density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2a density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. copyright (C) 2012S. Karger AG, Base