Doppler Echocardiography of Normal and Abnormal Embryonic Mouse Heart

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Abstract
To evaluate normal embryonic mouse heart development using Doppler echocardiography and to quantify changes in normal embryonic mouse cardiac function with increasing gestational age from the time of cardiac septation, a new method was applied using Doppler echocardiography. Trisomic embryos were screened to evaluate a model of abnormal cardiac anatomy. The development of the embryonic heart in mice has been well studied anatomically, but there are limited physiologic 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 trisomy embryos that die during gestation and have cardiac failure. To analyze early normal embryonic heart hemodynamics, Doppler echocardiograms were performed on n = 129 C57B1/6J mouse embryos from d 10 through 19 of gestation and 20 embryos with trisomy 16 (gestational d 11-14). The maximal blood velocities recorded at the inflow and outflow of the embryonic heart were analyzed for heart rate, peak early and peak late inflow and outflow velocities, and measurements were made of systolic ejection, filling, and other time intervals normalized for heart rate. A high velocity holosystolic or diastolic velocity with altered time intervals was identified as atrioventricular or semilunar valvular regurgitation, respectively. Inflow and outflow velocities increased with increasing gestational age. The time period of isovolemic contraction time was present before and undetectable after gestational d 17, whereas the total filling time increased. Ejection time and isovolemic relaxation time had no significant change. No valvular regurgitation was detected in normal embryos. These echocardiographic patterns are similar to those observed for human embryos. Abnormal Doppler findings were present (inflow or outflow valvular regurgitation) in 55% of trisomy 16 embryos. Echocardiographic data can now be obtained beginning at d 11 in the mouse embryo for analyses relating to abnormal heart development. A noninvasive technique may be invaluable to monitor the physiologic 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 regurgitation may be present and detectable with structural valvular abnormalities or failing cardiac physiology. The mouse embryo is an appropriate animal model to analyze normal and abnormal mammalian heart development and function.