34 Long term effects of pregnancy on cardiovascular function: serial echocardiograms in non-hypertensive and hypertensive mice

Abstract

The specific impact of pregnancy on long term cardiovascular function (CVF) is challenging to study due to multiple confounders. A mouse model allows us to study the effect of pregnancy while controlling other factors. Our aim was to evaluate CVF in pregnancy and up to the equivalent of 1 year postpartum (PP) in non-hypertensive and hypertensive murine models compared to non-pregnant (NP) controls. Wild type (WT) and endothelial nitric oxide synthase (eNOS) heterozygous females were used to generate the non-hypertensive and moderately hypertensive models, respectively. Mice were divided between pregnant/PP and NP groups. Mice underwent echocardiography (echo) at age-matched time points: 0 = baseline (10 weeks of age), 1 = gestational day 18.5, 2 = 1 week PP or 4 months of life, 3 = 2 months PP or 6 months of life. After assessing mouse weights, echos were performed under anesthesia using the Vevo system. Left ventricle (LV) parameters were measured three times and averaged: ejection fraction (EF), fractional shortening (FS), cardiac output (CO), stroke volume (SV), LV mass index (LVMI), and ascending aortic (AA) diameter and velocity. Two-way and RM ANOVA were used for statistical analysis, followed by Holm-Sidak post hoc test. 121 murine echos were performed. In WT mice, pregnancy significantly increased LVMI, a measure of LV hypertrophy (Fig. 1A). Pregnancy had no effect on LVMI in the hypertensive eNOS mice (Fig. 1B). EF and FS was not different between the pregnant and NP groups in both WT and eNOS animals. In WT mice, CO, SV, and AA diameter and velocity were persistently increased PP compared to the NP; while in the eNOS mice, they were increased only in the initial PP period (Table 1). Mouse weights were not different among groups. In these animal models, pregnancy persistently adversely impacts CVF in non-hypertensive mice. However, only vascular function is altered after pregnancy in the setting of preexisting hypertension (eNOS). A longer study period is needed to determine if these findings contribute to early-onset of maternal cardiovascular disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)