The effects of prenatal lipopolysaccharide on cardiac function

Abstract

Low birth weight has been strongly associated with cardiovascular disease in adulthood. The first report of poor maternal nutrition being associated with cardiovascular disorders in offspring was from Dr. David Barker who showed that people had an increased risk of death from cardiovascular disease if they were small at birth. There is also substantial evidence that maternal infection/inflammation are likely contributors to low birth weight. We tested the hypothesis that prenatal exposure of lipopolysaccharide (LPS) decreases cardiac function in adulthood.Pregnant C57BL/6J mice were treated with a single dose of LPS (2 ug/mouse) i.p. or vehicle at gestation E16. Basal cardiac performance and responses to stress (isoproterenol, 2.5 mg/kg, ip) were determined in male offspring at 8 weeks with echocardiogram. Offspring were sacrificed and cardiac tissues were collected.Compared with the control group, offspring of LPS‐treated dam had slower growth rate (body weight at 8w: 22.1±1.3 vs. 24.6±2.1g, p<0.05) with decreased cardiac output (CO, 21.8±3.9 vs. 25.7±2.1 ml/min, p<0.05), signifying an impaired cardiac contractility. In addition, offspring with prenatal LPS exposure seemed to have less increase of CO after stress test, suggesting a decreased cardiac reserve.Our data suggest that prenatal inflammation has long term effects on cardiac function. Further mechanistic studies are undergoing.