Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

Abstract

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 csection, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O 2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O 2 (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.

Long term effects of maternal protein restriction on postnatal lung alveoli development of rat offspring

“…Similar findings of the body weight, lung weight and lung weight to body weight ratio in protein restricted group were mentioned by other studies [14,17]. The decrease in body weight, lung weight and lung weight to body weight ratio at day 1 and 14 may be due to decrease in the amount of protein content in the body and organs which was essential component of tissue elements, but the increased lung weight to body weight ratio at 2 months may be due to decrease in lung weight more than body weight or increase in the body weight which caused by fluid retention resulted from hypo-albuminaemia.…”

Functional assessment of hyperoxia-induced lung injury after preterm birth in the rabbit

“…The smallest species in which in utero manipulation like intra-amniotic or direct intravenous or intratracheal injections during the saccular or initial alveolar phase of development can be modeled is the rabbit. The use of preterm born rabbits has been previously described to study neonatal nutrition (5), the antioxidant system (31), intraventricular hemorrhage (3), the effect of betamethasone (29), or hyperoxia exposure (21,22). The latter two studies have provided very important information about the housing and feeding of premature rabbits as well as insights in the lung pathology after hyperoxic exposure.…”

“…The feeding consisted of a mixture of soybean oil (Intralipid 30%, 270 kcal/100 ml; Fresenius Kabi), pure casein (100% Casein, 360 kcal/100 mg; Optimum Nutrition), pediatric milk formula (Nutrilon HA nr 2, 453 kcal/100 mg; Nutricia), and water. This mixture gives a nutritional value of 16 g lipids, 5.3 g proteins, 2.7 g carbohydrates (176 kcal in total)/100 ml and was chosen in accordance to prior studies using a preterm rabbit model (21,22). The amount of feeding steadily increased from 80 to 100 to 150 to finally 200 mg·kg Ϫ1 ·day Ϫ1 on days 0, 1, 2, and 3 (until 7), respectively.…”

“…The amount of feeding steadily increased from 80 to 100 to 150 to finally 200 mg·kg Ϫ1 ·day Ϫ1 on days 0, 1, 2, and 3 (until 7), respectively. On day 2, vitamin K was administered intramuscularly (0.002 mg/kg, Konakion pediatrique; Roche, Basel, Switzerland), and from that point pups were given a daily intramuscular injection of benzylpenicillin (20,000 E·kg Ϫ1 ·day Ϫ1 , Penicilline; Kela, Sint-Niklaas, Belgium) and amikacin (20 mg·kg Ϫ1 ·day Ϫ1 , Amukin; Bristol-Myers-Squibb) (21,22). The pups remained in the incubator except for the feeding moments for which they were removed from the incubator for a maximum of 10 min/feed.…”

“…Even more important, rabbits start alveolizing before birth, as do humans (26). Our own experience (8,28,30) combined with the findings from published data like the preterm rabbit model described by Mascaretti et al (21) and Mataloun et al (21,22) led us to select rabbits as the best candidate model to study the effects of hyperoxia after preterm birth. Our aim was to create a model with a full methodological description, including histological and immunohistochemical outcomes, as well as functional lung tests.…”