Echocardiographic assessment of embryonic and fetal mouse heart development: a focus on haemodynamics and morphology

Abstract

Background: Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system.

Methods: A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n = 105).

Results: Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed.

Conclusion: High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts.

Figure 1

Development of LV inflow patterns. (a) Shows an example of a pulsed-wave Doppler recording across the MV at 17.5 dpc. (a′) Indicates the magnification of the boxed area in (a) in which the individual time intervals are indicated, that is, RR, DFT, IVCT, ET, and IVRT. (b) Through (e) indicates the course of the DFT, ET, IVCT, and IVRT, respectively, throughout embryonic/fetal life. All values in (b–e) are expressed as percentage of the RR.

Figure 2

Cardiac morphology and FS% calculation. (a) Shows a reconstruction of the anterior view of an embryonic heart of 12.5 dpc. The myocardium is indicated in grey transparent. The LA and RA are indicated in transparent dark grey. The LV and RV lumen are indicated in red and blue, respectively. Note that the outflow tract lumen (purple) is positioned completely above the future RV, which is surrounded by large outflow tract cushions (green transparent). At these stages development of the IVS has not yet completed leading to a direct connection between the LV and RV via the interventricular foramen (arrow). (b) Anterior view of an early fetal heart of 14.5 dpc. At this stage IVS development has been completed and four separate cardiac chambers can be identified. The outflow tract consists of a separate Ao and PT including their valve apparatus, which at these stages mainly consist of cushion tissue (green transparent). (c) Anterior view of a late fetal heart of 17.5 dpc. At this stage the heart shows a mature morphological phenotype. (d) Schematic representation of LV and RV diameters and (e) FS% at the three consecutive stages of development.

Figure 3

Development of LV and RV inflow patterns. The graphs represent the course of the E/A ratio (a, b), peak-E wave (c, d), and peak-A wave (e, f) across the developing MV and TV at the three subsequent developmental stages.

Figure 4

Pulsed-wave Doppler flow measurements in the cOFT, Ao, and PT. The graph demonstrates the significant increase of the peak blood flow measured in the cOFT at 12.5 and Ao and PT at 14.5 and 17.5 dpc.