Pulmonary Vascular Disease in Bronchopulmonary Dysplasia

Grenolds, Alicia; Mourani, Peter M.

doi:10.21693/1933-088x-15.2.92

Cited by 8 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with other investigators who have shown impaired cardiac function and fibrosis in adult rodents exposed to neonatal hyperoxia (Bertagnolli et al, ). It should however be noted that the LV dysfunction in our study may be secondary to pulmonary hypertension (Abman, Grenolds, & Mourani, ), as other studies in our lab have demonstrated significantly increased RV systolic pressure in young rats exposed to neonatal hyperoxia (Bryan et al, ). In our present study, we did not evaluate the degree of pulmonary hypertension but we postulate that our current findings of impaired LV function may be secondary to the effects of neonatal O 2 exposure on the systemic vasculature or potentially secondary to pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 46%

Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats

et al. 2020

View full text Add to dashboard Cite

Supplemental oxygen (O 2 ) therapy in preterm infants impairs lung development, but the impact of O 2 on long-term systemic vascular structure and function has not been well-explored. The present study tested the hypothesis that neonatal O 2 therapy induces long-term structural and functional alterations in the systemic vasculature, resulting in vascular stiffness observed in children and young adults born preterm.Newborn Sprague-Dawley rats were exposed to normoxia (21% O 2 ) or hyperoxia (85% O 2 ) for 1 and 3 weeks. A subgroup exposed to 3 weeks hyperoxia was recovered in normoxia for an additional 3 weeks. Aortic stiffness was assessed by pulse wave velocity (PWV) using Doppler ultrasound and pressure myography. Aorta remodeling was assessed by collagen deposition and expression. Left ventricular (LV) function was assessed by echocardiography. We found that neonatal hyperoxia exposure increased vascular stiffness at 3 weeks, which persisted after normoxic recovery at 6 weeks of age. These findings were accompanied by increased PWV, aortic remodeling, and altered LV function as evidenced by decreased ejection fraction, cardiac output, and stroke volume. Importantly, these functional changes were associated with increased collagen deposition in the aorta. Together, these findings demonstrate that neonatal hyperoxia induces early and sustained biomechanical alterations in the systemic vasculature and impairs LV function. Early identification of preterm infants who are at risk of developing systemic vascular dysfunction will be crucial in developing targeted prevention strategies that may improve the long-term cardiovascular outcomes in this vulnerable population. K E Y W O R D Sdevelopmental programming, LV dysfunction, neonatal hyperoxia, systemic vascular stiffness

show abstract

Section: Discussionmentioning

confidence: 46%

Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Taken together, these results suggest that upregulation of these important inflammatory and fibrotic mediators contributes to the induction of BPD pathology by O 2 -EVs in the receipt rats. Although many cell types in the lung could be the targets of circulating EVs, we focused our investigation on PVEC because PVEC would have direct contact with the circulating nanoparticles, and their injury can lead to abnormal vascular development in BPD 37 . Utilizing in vitro PVEC cultures, we demonstrated that O 2 -EVs decreased cell proliferation and increased cell death.…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia-activated circulating extracellular vesicles induce lung and brain injury in neonatal rats

Ali

Zambrano

Duncan

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants.

show abstract

“…4,9 On the other hand, multiple studies have demonstrated that low DLCO is a predictor of the presence of PH in ILD. 9,31,[37][38][39] Steen and colleagues observed that an FVC:DLCO ratio of >1.4 was an excellent predictor of development of isolated PAH. 40 Seibold reported that an FVC:DLCO ratio of ≥1.8 was a good predictor of death in SSc, while Trad and colleagues found a ratio of ≥2 to predict survival.…”

Section: Diagnosis Screening and Monitoringmentioning

confidence: 99%

“…36 The measurement of the main PA and ascending aorta diameters should be done at the level where the PA bifurcates (when both the right and left PA appear to be of similar size) using electronic calipers. 37 Magnetic Resonance Imaging: Magnetic resonance imaging is more accurate than a computed tomography chest scan. PA diameter and PA-aorta ratio cutoff values >34 mm and >1.1 yielded specificities of 98% and 100%, with corresponding sensitivities of 65% and 50% and positive predictive values of 98% and 100%.…”

Section: Imagingmentioning

confidence: 99%

Full Issue PDF

2021

Advances in Pulmonary Hypertension

View full text Add to dashboard Cite

show abstract

Pulmonary Vascular Disease in Bronchopulmonary Dysplasia

Cited by 8 publications

References 48 publications

Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats

Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats

Hyperoxia-activated circulating extracellular vesicles induce lung and brain injury in neonatal rats

Full Issue PDF

Contact Info

Product

Resources

About