Structural coronary artery remodelling in the rabbit fetus as a result of intrauterine growth restriction

Patricia Garcia-Canadilla,Tom De Vries,Eduard Gratacos,Bart Bijnens,Fatima Crispi,Anne Bonnin,Chong Zhang,Anna Gonzalez-Tendero,Rogelio Cruz-Martinez

doi:10.1371/journal.pone.0218192

Abstract

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries’ lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure.

Highlights

Intrauterine growth restriction (IUGR), linked to placental insufficiency, is one of the leading causes of perinatal mortality and long-term morbidity [1,2] affecting up to 10% of pregnancies
While there is a trend towards a decrease of left ventricular mass (LVM) in IUGR compared to controls (p value = 0.061), the LVM to body weight ratio was similar among groups
When left ventricle (LV) wall thickness was normalised to LVM, IUGR fetuses showed increased normalised wall thickness compared to controls suggesting that IUGR fetuses have hypertrophic hearts this difference was not statistically significant (6.88 ± 0.54 vs. 5.19 ± 0.75, p value = 0.061 calculated with Student’s t-test)

Summary

Introduction

Intrauterine growth restriction (IUGR), linked to placental insufficiency, is one of the leading causes of perinatal mortality and long-term morbidity [1,2] affecting up to 10% of pregnancies. IUGR refers to the condition by which a fetus does not reach their predefined genetic potential. Structural coronary artery remodeling in the IUGR fetus. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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