DOPPLER-ECHOCARDIOGRAPHY OF NORMAL AND ABNORMAL EMBRYONIC MOUSE HEART

To evaluate normal embryonic mouse heart development using Doppler ech ocardiography and to quantify changes in normal embryonic mouse cardia c function with increasing gestational age from the time of cardiac se ptation, a new method was applied using Doppler echocardiography. Tris omic embryos were screened to evaluate a model of abnormal cardiac ana tomy. The development of the embryonic heart in mice has been well stu died anatomically, but there are limited physiologic studies, A new me thod has been developed to assess the mouse fetal heart in a similar f ashion 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 hemo dynamics, Doppler echocardiograms were performed on n = 129 C57B1/6J m ouse embryos from d 10 through 19 of gestation and 20 embryos with tri somy 16 (gestational d 11-14), The maximal blood velocities recorded a t the inflow and outflow of the embryonic heart were analyzed for hear t rate, peak early and peak late inflow and outflow velocities, and me asurements were made of systolic ejection, filling, and other time int ervals normalized for heart rate. A high velocity holosystolic or dias tolic velocity with altered time intervals was identified as atriovent ricular 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 undetect able after gestational d 17, whereas the total filling time increased, Ejection time and isovolemic relaxation time had no significant chang e, No valvular regurgitation was detected in normal embryos. These ech ocardiographic patterns are similar to those observed for human embryo s. Abnormal Doppler findings were present (inflow or outflow valvular regurgitation) in 55% of trisomy 16 embryos, Echocardiographic data ca n now be obtained beginning at d 11 in the mouse embryo for analyses r elating to abnormal heart development. A noninvasive technique may be invaluable to monitor the physiologic condition of embryos within a li tter and to detect and monitor those embryos where heart defects may b e expected. Qualitative markers of embryonic congestive heart failure such as valvular regurgitation may be present and detectable with stru ctural valvular abnormalities or failing cardiac physiology, The mouse embryo is an appropriate animal model to analyze normal and abnormal mammalian heart development and function.