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Chronic lung injury in preterm lambs: disordered pulmonary elastin deposition
R A Pierce1, K H Albertine, B C Starcher
1Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Insights
Mechanical ventilation in premature infants can harm lung development, leading to abnormal elastin accumulation. This study suggests excessive elastin production contributes to chronic lung injury in neonates requiring prolonged respiratory support.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Developmental Biology
Background:
- Prolonged mechanical ventilation in premature neonates is linked to abnormal lung development and chronic lung disease, specifically bronchopulmonary dysplasia.
- Impaired alveolar development is a key characteristic of bronchopulmonary dysplasia.
Purpose of the Study:
- To investigate the impact of mechanical ventilation on lung elastin expression in preterm lambs.
- To determine if altered elastin production contributes to lung injury associated with mechanical ventilation.
Main Methods:
- Studied lung tissue from 10 preterm lambs ventilated for 3-4 weeks at different rates and tidal volumes.
- Assessed lung morphology, elastin accumulation (desmosine content), and tropoelastin mRNA expression.
- Utilized in situ hybridization to localize tropoelastin mRNA expression.
Main Results:
- Mechanical ventilation led to increased elastin accumulation and abnormal lung morphology in preterm lambs.
- Significantly increased desmosine content (elastin marker) was observed in the 20 breaths/min group.
- Tropoelastin mRNA expression was elevated in both ventilated groups, localized to areas of elastin accumulation.
Conclusions:
- Excessive production and accumulation of elastin are associated with chronic lung injury in neonates undergoing prolonged mechanical ventilation.
- Altered elastin expression may play a critical role in the pathogenesis of bronchopulmonary dysplasia.
- These findings highlight the potential for targeted therapies to modulate elastin in neonatal lung injury.
Abstract:
Prolonged mechanical ventilation of premature neonates is often associated with abnormal morphological development of the lung and chronic lung disease, sometimes called bronchopulmonary dysplasia (BPD). Impaired alveolar development is a hallmark of this disease. To better understand the effects of mechanical ventilation on lung elastin expression, we studied lung tissue from 10 preterm lambs (gestation = 125 days; term = 148 days) mechanically ventilated for 3-4 wk at a respirator rate of 20 breaths/min and tidal volume of 15 +/- 5 ml/kg (n = 5) or 60 breaths/min and tidal volume of 5 +/- 2 ml/kg (n = 5). Histopathology showed increased elastin accumulation and abnormal morphological development in the ventilated groups. Postmortem lung desmosine content was increased significantly in the 20 breaths/min group. Tropoelastin mRNA expression was increased in both ventilated groups. In situ hybridization localized increased tropoelastin mRNA expression to sites of accumulated elastin in extended alveolar walls with scant, attenuated secondary crests. Lung collagen content, as assessed by the amount of hydroxyproline in lung tissue, was similar to controls. These data suggest that excessive production and accumulation of elastin is associated with chronic lung injury from prolonged mechanical ventilation after premature birth.