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Publication : Developmental changes in ventricular diastolic function correlate with changes in ventricular myoarchitecture in normal mouse embryos.

First Author  Ishiwata T Year  2003
Journal  Circ Res Volume  93
Issue  9 Pages  857-65
PubMed ID  14551244 Mgi Jnum  J:109386
Mgi Id  MGI:3628858 Doi  10.1161/01.RES.0000100389.57520.1A
Citation  Ishiwata T, et al. (2003) Developmental changes in ventricular diastolic function correlate with changes in ventricular myoarchitecture in normal mouse embryos. Circ Res 93(9):857-65
abstractText  Both genetic and epigenetic factors, such as abnormal hemodynamics, affect cardiac morphogenesis and the pathogenesis of congenital heart disease. Diastolic function is an important determinant of cardiac function, and tools for evaluating diastolic function in the embryo would be very valuable for assessment of cardiac performance. Using histological measurements of ventricular myoarchitecture, Doppler assessment of ventricular inflow velocities, and direct measurement of ventricular pressure, we investigated developmental changes of ventricular diastolic function in the mouse embryos from embryonic days 9.5 to 19.5. Regression analysis showed that peak velocity of A wave (an index of passive compliance) correlated with the area of trabecular myocardium in right ventricle (RV) (r2=0.92, P<0.0001) and left ventricle (LV) (r2=0.93, P<0.0001). Peak velocity of E wave (an index of active relaxation) exponentially correlated with the area of compact myocardium in RV (r2=0.98, P<0.0001) and LV (r2=0.97, P<0.0001). We used these techniques to analyze FOG-2 null embryos. FOG-2 null embryos had thin compact myocardium, higher EDP and E/A ratio, smaller -dP/dt, and diminished sucking pressure than wild-type littermates, indicating that decreased ventricular diastolic function might be the primary cause of embryonic lethality. In conclusion, during embryogenesis the development of compact myocardium tightly regulates the development of ventricular distensibility. Our study in normal mice forms the basis for future studies of embryonic cardiac function in genetically manipulated mice with abnormalities of the cardiovascular system.
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