Abstract
AimsThe impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Methods and ResultsPregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O2 for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O2 than in saline/RA mice. Isolated cardiomyocytes from LPS/O2 mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O2 mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O2 mice.ConclusionThese results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health.
Highlights
The impact of maternal health and the neonatal environment on the development of adult cardiovascular disease has recently been appreciated
Isolated cardiomyocytes from LPS/O2 mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/room air (RA) controls. a-/b Myosin Heavy Chain (b-MHC) ratio was increased and Connexin-43 levels decreased in LPS/O2 mice at 8 weeks
These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health
Summary
The impact of maternal health and the neonatal environment on the development of adult cardiovascular disease has recently been appreciated. Most notable are the investigations by Barker and coworkers [1] correlating low birth weight and increased cardiovascular mortality in adulthood. Since the first observations by Barker [2], several studies have expanded this association with low birth weight to include the development of hypertension, insulin resistance, and coronary artery disease. Animal models have not identified specific mechanisms for the influences of birth weight on adult health.[5,6,7] the impact of intrauterine and early neonatal influences on developmental programming due to low birth weight or early gestational age and cardiovascular health warrants further investigations.[7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call