YH Gui, KK Linask, JC Huhta

Objectives: 1) To evaluate normal embryonic mouse heart development using Doppler echocardiography. 2) To quantify changes in normal embryonic mouse cardiac function with increasing gestational age from the time of cardiac septation. 3) To screen and evaluate a model of abnormal cardiac anatomy in trisomic embryos.

The development of the embryonic heart in mice has been well studied anatomically, but there are limited physiological studies. A new method has been developed to assess the mouse fetal heart in a similar fashion to the current use of echocardiography in the chick embryo and the human fetus. This method was applied to normal mouse embryos known to survive and to abnormal trisomic embryos which have cardiac failure and die during gestation. For the analysis of early normal embryonic heart haemodynamics, Doppler echocardiograms were performed on 129 C57B1/6J mouse embryos from Day 10 (D10) through D19 of gestation and 20 embryos with trisomy 16 (D11-D14). The maximal blood velocities recorded at the inflow and outflow of the embryonic heart were analysed for heart rate, peak early and peak late inflow and outflow velocities; the systolic ejection and filling time intervals adjusted for heart rate were measured. A high velocity holosystolic and diastolic velocity with altered time intervals were identified as atrioventricular and semilunar valvular regurgitation, respectively. Heart rate increased with increasing gestational age. The isovolemic contraction time decreased during development to undetectable levels on D17, while the total filling time increased by a similar amount. Ejection time and isovolemic relaxation time showed no significant change. No valvular regurgitation was detected. These echocardiographic patterns are similar to those observed for human embryos. Abnormal Doppler findings (inflow or outflow valvular regurgitation) were present in 55% of trisomy 16 embryos. These echocardiographic data can thus serve as a baseline for analyses relating to abnormal heart development. A non-invasive technique may be invaluable to monitor the physiological condition of embryos within a litter, and to detect and monitor those embryos where heart defects may be expected. Qualitative markers of embryonic congestive heart failure such as valvular abnormalities or failing cardiac physiology can be studied. The mouse embryo is an appropriate animal model to analyse normal and abnormal mammalian heart development and function.