Abstract 17219: Increased Aortic Stiffness Following Intrauterine Exposure to Chronic Hypoxia in Rats

Abstract

Background: We have previously demonstrated in rats that fetal hypoxia is associated with altered left ventricular (LV) diastolic function beginning in early postnatal life (2 weeks). In the present study we hypothesized that intrauterine hypoxia exposure alters aortic stiffness which may contribute to the evolution of myocardial dysfunction after birth. Methods: Six pregnant rats were exposed to hypoxic conditions (11.5% FiO2) from E15-21and 3 were maintained in normoxic conditions. After delivery, 4 neonatal rats from each group were examined longitudinally at day 1, 3, and week 1, 2, 4, 8 for changes in aortic stiffness. Pups were anesthetized by face mask with 1.5% isoflurane. Aortic stiffness was assessed by measuring the pulse wave velocity (PWV) in the ascending aorta at 3 points: 1. Proximal to the branch of the first brachiocephalic artery 2. At the level of the diaphragm and 3. Just above the aortic bifurcation into the iliac arteries. T1 was the time interval from the peak of the R wave by ECG to onset of flow in the ascending aorta and T2 from peak of the R wave to onset of flow in either the mid aorta or distal aorta. The distance from the suprasternal notch to the subxiphoid process and to the anterior superior iliac spine was measured in each animal. The PWV was calculated using the following equation: [distance/(T2-T1)]. Three consecutive tracings were assessed and the PWV averaged for each study. Statistical analysis was performed using a 2-way ANOVA. Results: In pups exposed to fetal hypoxia, PWV was significantly increased (p≤0.001) compared to controls at day 1 (4.8±1.5 vs. 2.3±0.2 m/s), day 3 (5.5±0.3 vs. 2.6±0.1 m/s) and week 1 (4.4±0.4 vs. 2.8±0.1 m/s). Interestingly, there was an interaction of time and fetal exposure (p=0.006) whereby PWV values converged from weeks 2 - 8 such that fetal exposure to hypoxia no longer had an effect. No correlation was found between LV diastolic function parameters and aortic PWV in the fetal hypoxia rats at any postnatal age. Conclusion: Prenatal exposure to hypoxia was associated with increased aortic stiffness during early development. The lack of a relationship between LV diastolic function and aortic stiffness could suggest these represent independent effects of fetal hypoxia exposure.