The cardiac cycle of the embryonic heart has a distinct atrial and ventricular systole and diastole. Cardiac output is affected by the reservoir, conduit, and pump functions of the atrium. Varying the magnitudes of various system parameters such as heart rate, atrial- ventricular coupling and the diastolic properties in the embryonic heart. The combined analysis of atrial and ventricular function is integral to our comprehension of normal and experimentally altered cardiovascular performance. Our long term aim is to understand the integrated cardiovascular function during morphogenesis of the cardiovascular system. This is fundamental in order to mathematically model atrial/ventricular coupling. We hypothesize that there is optimal hemodynamic and mechanical coupling of atrial and ventricular function in the embryonic cardiovascular system. Our experimental model is the stage 16 to 29 white Leghorn chick embryo during the transaction of ventricular geometry from a smooth-walled to a trabecular chamber. Our experiment methods are described in the Physiology Core, and include the measurements of servonull pressure, Doppler velocity and video imaging.
Our specific aims are: Define atrial pump function, and the atrioventricular pressure gradient during normal cardiovascular development and during acute alterations in preload and calcium availability. Define the transfer of blood pressure flow between the embryonic atrium and ventricle during alterations in heart rate produces by thermal probe application, embryo hypothermia, and sinus venosus pacing. Define the mechanical and biochemical basis for diastolic relaxation and filling during normal cardiovascular development, and following acute alterations in preload, calcium availability, and ventricular growth acceleration produced by conotruncal banding and growth declaration produced by partial left atrial ligation. This project defines the functional interaction of the embryonic atrium and ventricle during a wide range of acute and chronic alterations in hemodynamic performance. The analysis of experimental results within the framework of a closed loop system provides crucial information of the regulation of cardiovascular function. This integrated analysis then becomes the foundation for the structural and functional analysis of genetically altered cardiovascular systems in experimental models, and ultimately, aids in defining the underlying etiologies of congenital cardiovascular malformations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL051498-03
Application #
5214095
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Miller, Christine E; Wong, Chandra L; Sedmera, David (2003) Pressure overload alters stress-strain properties of the developing chick heart. Am J Physiol Heart Circ Physiol 285:H1849-56
Sedmera, David; Hu, Norman; Weiss, Karen M et al. (2002) Cellular changes in experimental left heart hypoplasia. Anat Rec 267:137-45
Ursem, N T; Clark, E B; Pagotto, L T et al. (2001) Fetal heart rate and umbilical artery velocity variability in fetuses with congenital cardiac defects: a preliminary study. Ultrasound Obstet Gynecol 18:135-40
Struijk, P C; Ursem, N T; Mathews, J et al. (2001) Power spectrum analysis of heart rate and blood flow velocity variability measured in the umbilical and uterine arteries in early pregnancy: a comparative study. Ultrasound Obstet Gynecol 17:316-21
Miller, C E; Wong, C L (2000) Trabeculated embryonic myocardium shows rapid stress relaxation and non-quasi-linear viscoelastic behavior. J Biomech 33:615-22
Tobita, K; Keller, B B (2000) Right and left ventricular wall deformation patterns in normal and left heart hypoplasia chick embryos. Am J Physiol Heart Circ Physiol 279:H959-69
Miller, C E; Donlon, K J; Toia, L et al. (2000) Cyclic strain induces proliferation of cultured embryonic heart cells. In Vitro Cell Dev Biol Anim 36:633-9
Yoshigi, M; Knott, G D; Keller, B B (2000) Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB. Comput Methods Programs Biomed 63:29-41
MacLennan, M J; Keller, B B (1999) Umbilical arterial blood flow in the mouse embryo during development and following acutely increased heart rate. Ultrasound Med Biol 25:361-70
Ursem, N T; Clark, E B; Keller, B B et al. (1999) Fetal heart rate and umbilical artery velocity variability in pregnancies complicated by insulin-dependent diabetes mellitus. Ultrasound Obstet Gynecol 13:312-6

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