Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR

Yichen Dai,Choon Hwai Yap,Ching Kit Chen,Dan Zhao

doi:10.1038/s41390-020-01356-8

Abstract

BackgroundIntrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans.MethodsUnilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20.ResultsGrowth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses.ConclusionsDespite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology.ImpactAnimal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses.We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation.Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS.Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction.Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

Highlights

Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its growth potential[1] and is often caused by placental insufficiency, leading to inadequate nutrients and oxygen supply to the fetus.[2,3,4] IUGR occurs in 3–10%5,6 of pregnancies, and is one of the major causes of prenatal and perinatal mortality and morbidity, but yet there is currently no proven strategy to prevent or treat it.[7]
Weight and size Fetal and placental weights measured at the time of harvest at E20 are shown in Fig. 1A, B and Table 2
A good understanding of the cardiac function in these models will be important, as will an assessment of how similar the cardiac function is to that of human fetuses. We performed such an investigation on the uterine artery ligation rat model, and from our measurements, we found evidence suggesting cardiac dysfunction that was observed in IUGR human fetuses, but we found essential differences from human fetuses

Summary

Introduction

Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its growth potential[1] and is often caused by placental insufficiency, leading to inadequate nutrients and oxygen supply to the fetus.[2,3,4] IUGR occurs in 3–10%5,6 of pregnancies, and is one of the major causes of prenatal and perinatal mortality and morbidity, but yet there is currently no proven strategy to prevent or treat it.[7]. Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. Growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. CONCLUSIONS: Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology

Methods

Results

Discussion

Conclusion