Two common lung diseases in premature infants, bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH), might be detected by echocardiography at an earlier point than previously thought, reported researchers at Baylor College of Medicine, who used the device to detect PH in neonatal mice.
The study was published in the International Journal of Chronic Obstructive Pulmonary Disease, and titled “Phenotypic assessment of pulmonary hypertension using high-resolution echocardiography is feasible in neonatal mice with experimental bronchopulmonary dysplasia and pulmonary hypertension: a step toward preventing chronic obstructive pulmonary disease.”
BPD in infants, like chronic obstructive pulmonary disease (COPD) in adults, is a chronic lung disorder characterized by alveolar simplification. One-third of the infants with severe BPD go on to develop pulmonary hypertension.
The lack of an appropriate small animal model where echocardiography (Echo) can demonstrate PH is one of the major barriers to understanding the disease’s molecular mechanisms, a necessary step in developing therapies to prevent or treat PH in BPD patients. Progress toward improved treatments has also been limited, in part, by the lack of advanced imaging techniques to detect PH and lung damage at earlier time points in animals, and test treatments against them.
For this reason, the researchers developed an animal model of experimental BPD and PH, and investigated the feasibility of Echo to diagnose PH in neonatal mice.
To stimulate inflammation and oxidative stress, two features of PH which can damage cells and interrupt lung development, the investigators exposed newborn mice to 70% oxygen (hyperoxia) for 14 days, while control animals received 21% oxygen or regular air.
Researchers found that newborn mice exposed to hyperoxia developed lung oxidative stress, inflammation, and lungs that resembled those of infants with BPD and PH. In addition, echocardiography assessments performed in these young mice revealed they had developed PH.
“It’s important to understand not only the pathology, but also the functional aspect of pulmonary hypertension,” said Binoy Shivanna, assistant professor of pediatrics-neonatology at Baylor and Texas Children’s Hospital, in a news release. “This is where the echocardiography test, a non-invasive test that uses high frequency sound waves to take pictures of the heart, comes in.”
Presently, echocardiography examinations have been executed in mice at four weeks of age, which could be too late to intervene. In the study, the team demonstrated that it is possible to detect PH earlier, meaning that interventions might take place sooner.
The animal model developed may offer a way to identify pathophysiological mechanisms that contribute to PH, and to pursue therapeutic strategies to prevent or treat BPD and PH in preterm infants, likely preventing adult-onset COPD in former BPD patients.
Study findings also have important implications for research in the prevention and treatment of other congenital disorders — like pulmonary hypoplasia, congenital diaphragmatic hernia, and congenital heart diseases — associated with PH in infants.
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