Adverse perinatal environment contributes to altered cardiac development and function.

Epidemiological observations report an association between intrauterine growth restriction (IUGR) and cardiovascular diseases. Systemic maternal inflammation is the most common stress during pregnancy, leading to IUGR. We hypothesized that perinatal inflammation and hyperoxygenation induce discernible alterations in cardiomyocyte contractility and calcium signaling, causing early cardiac dysfunction. Pregnant C3H/HeN mice were injected with LPS or saline on embryonic day 16. Newborn mice were placed in 85% O2 or room air (RA) for 14 days. Pups born to LPS-injected dams had reduced birth weight. Echocardiographic measurements revealed that in vivo LV function was compromised in LPS/O2 mice as early as 3 days of life. Isolated cardiomyocytes from LPS/O2 mice at day 14 exhibited decreased sarcomere fractional shortening, along with decreased time-to-90% peak shortening. Calcium transient amplitude was greatest in LPS/O2 mice. SERCA2a mRNA and protein levels were increased and phospholamban mRNA levels were decreased in LPS/O2 mice. Phosphorylation of phospholamban was increased, along with Sorcin mRNA levels in LPS/O2 mice. Combined exposure to perinatal inflammation and hyperoxia resulted in growth restriction, in vivo and in vitro cardiac dysfunction, coinciding with humans and animal models of cardiac dysfunction. Expression of calcium handling proteins during the neonatal period was similar to that observed during fetal stages of development. Our data suggest that perinatal inflammation and hyperoxia exposure alter fetal development, resulting in early cardiac dysfunction.