Why the study?
Children who suffered neonatal oxidative injury have an increased risk of cardiopulmonary disease later in life, but the mechanistic underpinning and time course of progression require clarification for risk stratification.
Does neonatal oxidative injury alter cardiopulmonary haemodynamics during exercise and hypoxia in a swine model?
Does neonatal oxidative injury alter cardiopulmonary haemodynamics during exercise and hypoxia in a swine model?
Duration of neonatal oxidative injury in a swine model determines structural and functional cardiopulmonary remodelling, leading to increased pulmonary vascular resistance and nitric oxide dependency later in life.
May indicate persistent pulmonary vascular effects from neonatal hypoxia; hypothesis-generating for human PH risk.
), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16-28 days), while SHAM piglets were normoxia raised. Following recovery (>5 weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic challenge testing (HCT) and exercise with modulation of the nitric-oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure - suggesting left atrial under-filling - consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase-5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise. KEY POINTS: Children who suffered from neonatal oxidative injury, such as very preterm born infants, have increased risk of cardiopulmonary disease later in life. Risk stratification requires knowledge of the mechanistic underpinning and the time course of progression into cardiopulmonary disease. Exercise and hypoxic challenge testing showed that 10- to 12-week-old swine that previously experienced neonatal oxidative injury had increased pulmonary vascular resistance and nitric oxide dependency. Duration of neonatal oxidative injury was a determinant of structural and functional cardiopulmonary remodelling later in life. Remodelling of the right ventricle, as a result of prolonged neonatal oxidative injury, resulted in worse performance during exercise, but enabled better performance during the hypoxic challenge test. Increased nitric oxide dependency together with age- or comorbidity-related endothelial dysfunction may contribute to predisposition to pulmonary hypertension later in life.
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Steenhorst et al. (2022) studied this question.
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