Altered cardiovascular function at birth in growth-restricted preterm lambs

Area of Science:

• Neonatal physiology
• Cardiovascular research
• Fetal development

Background:

• Cardiovascular dysfunction at birth is linked to poor outcomes in preterm neonates with fetal growth restriction (FGR).
• This study investigates the cardiovascular transition in FGR preterm lambs compared to appropriately grown (AG) controls.

Purpose of the Study:

• To compare cardiovascular transition between FGR and AG preterm lambs.
• To examine mechanisms underlying cardiovascular dysfunction in FGR lambs.

Main Methods:

• Fetal growth restriction (FGR) induced in twin-bearing ewes; the twin served as the appropriately grown (AG) control.
• Lambs delivered at 0.8 gestation; arteries isolated for myography or lambs ventilated for 2 hours with inhaled nitric oxide (iNO) administration in a subgroup.
• Molecular assessment of the nitric oxide (NO) pathway in lung tissue.

Main Results:

• FGR lambs exhibited lower left ventricular output and cerebral blood flow (CBF), with higher systemic vascular resistance than AG lambs.
• iNO improved hemodynamics in FGR lambs but decreased CBF in AG lambs.
• FGR lamb arteries showed impaired NO donor sensitivity, enhanced vasodilation to Sildenafil/Sodium nitroprusside, and altered NO pathway gene expression.

Conclusions:

• Cardiovascular dysfunction at birth in preterm FGR newborns contributes to increased morbidity and mortality.
• Impaired nitric oxide (NO) signaling is a likely cause of abnormal vascular reactivity in FGR lambs.