NF‐kappaB in the lungs of premature rabbits during mechanical ventilation—comparison between conventional mechanical ventilation (CMV) and high‐frequency oscillation (HFO)

Abstract

The purpose of this study is to compare pulmonary nuclear factor-kappaB (NF-kappaB) activity of conventional mechanical ventilation (CMV) with that of high-frequency oscillation (HFO) in premature rabbit lungs. For surfactant-depleted model, we used premature rabbits in order to exclude the effect of lung lavage on the activation of NF-kappaB. The premature rabbits were delivered at a gestational age of 27 days by hysterotomy. Both modes of the ventilator were set at the same MAP and FiO(2). We used animals that had PCO(2) levels of approximately 50-mmHg. Animals were sacrificed after 1-hr ventilation with CMV or HFO. Then activity of pulmonary NF-kappaB was assessed. We observed that NF-kappaB activity was higher in the lungs of CMV compared with those of HFO, as measured by Western blot analysis. The activity level of NF-kappaB in the lungs measured by ELISA was significantly higher in CMV group than in HFO group. We conclude that a higher level of NF-kappaB activation was associated with CMV when compared to HFO.

Animal models of bronchopulmonary dysplasia. The preterm and term rabbit models

“…Both term and preterm rabbits (delivered between 27 and 29 days of gestation) have been used in short-term (Յ16 h) experiments involving mechanical ventilation. These models have tested the effects of the administration of surfactant (24,30,64,86), of varying conventional mechanical ventilation and oxygen strategies (52), and of conventional vs. high-frequency oscillatory ventilation (88), as well as the effects of conventional ventilation on SP-A and KGF (36). With animal weights ranging from ϳ25 to 35 g at 27 days gestation, the preterm model allowed ventilation via an 18-gauge catheter inserted into the trachea (30,88).…”

“…RABBIT MODELS OF BPD reach adolescence by the close of exposure at 5-6 wk (although, unlike the human, their alveoli are still developing rapidly at that stage), allowing early evaluation of near-adult animals following a neonatal perturbation (67). Rabbit models are also cost effective compared with larger animal models, but large enough to permit perturbations, including nebulized treatments, mechanical ventilation and pulmonary function testing, and easy isolation of individual cells, even among newborn or premature animals (1,30,36,52,64,86,88,95). Neonatal rabbits weigh ϳ50 g, slightly above the size of an adult mouse, and even premature (27-29 days) rabbits have weights in the range of a mouse's 30 g. The once-daily feeding behavior of term rabbits allows mothers to be placed in the exposure chamber for brief periods once daily, avoiding the need for gavage feeding or cross-fostering and rotating mothers to prevent oxygen toxicity to the mothers.…”

“…Furthermore, the term newborn recovery model has not been critically evaluated for morphometric similarities to or differences from the human infant recovering from BPD. Premature rabbit kits have been maintained briefly on mechanical ventilation, showing evidence that it is possible to manipulate the model in this manner (30,36,52,64,86,88). However, there are no published longer-term exposures to both hyperoxia and mechanical ventilation that would mimic more fully the exposures faced by the human premature infant.…”