Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood

Abstract

Intrauterine growth restriction (IUGR), a condition affecting 7-15% of all pregnancies, is associated with an increased mortality rate during adulthood. Several animal models have been developed to study the effects of IUGR during adulthood. However, the in vivo characteristics of these models are still unknown. The main aim of this work was to evaluate, in vivo, the effects of IUGR on cardiopulmonary structure and function during adulthood. Pregnant Sprague Dawley rats were exposed to hypoxic (12% O2) or normoxic (21% O2) environments between day 15 and 21 of pregnancy. Offspring were raised to 4 or 12 months old when a complete in vivo echocardiographic study was performed. In addition, ex vivo morphometry and isolated working heart experiments were performed. At birth, pups exposed to hypoxia had a smaller body weight and larger heart/body weight than controls. At 4 months of age, there were no significant differences between the groups. At 12 months of age, male but not female offspring exposed to prenatal hypoxia had smaller body weights and signs of left ventricular hypertrophy. In addition, both male and females animals exposed to prenatal hypoxia showed in vivo and ex vivo signs of left ventricular diastolic dysfunction and pulmonary hypertension by 12 months of age. Our study demonstrated that hypoxia-induced IUGR is associated with the development of chronic cardiopulmonary dysfunction during ageing. The implication of these findings is the potential usefulness of neonatal diagnosis as a predictor of cardiopulmonary outcomes during adulthood.