Systolic and Diastolic Ventricular Function Assessed by Pressure-Volume Loops in the Stage 21 Venous Clipped Chick Embryo

Abstract

Cardiac pressure-volume relations enable quantification of intrinsic ventricular diastolic and systolic properties independent of loading conditions. The use of pressure-volume loop analysis in early stages of development could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. The venous clip model is an intervention model for the chick embryo in which permanent obstruction of the right lateral vitelline vein temporarily reduces the mechanical load on the embryonic myocardium and induces a spectrum of outflow tract anomalies. We used pressure-volume loop analysis of the embryonic chick heart at stage 21 (3.5 d of incubation) to investigate whether the development of ventricular function is affected by venous clipping at stage 17, compared with normal control embryos. Steady state hemodynamic parameters demonstrated no significant differences between the venous clipped and control embryos. However, analysis of pressure-volume relations showed a significantly lower end-systolic elastance in the clipped embryos (slope of the end-systolic pressure-volume relation: 5.68 Ϯ 0.85 versus 11.76 Ϯ 2.70 mm Hg/L, p Ͻ 0.05), indicating reduced contractility. Diastolic stiffness tended to be increased in the clipped embryos (slope of end-diastolic pressure-volume relation: 2.74 Ϯ 0.56 versus 1.67 Ϯ 0.21, p ϭ 0.103), but the difference did not reach statistical significance. Animal models are required to study mechanisms of early cardiovascular development. The chick embryo has been used as a model for many decades because the embryonic chick heart resembles the developing human heart in many aspects (1,2). The intricate relationship between hemodynamics and cardiac morphogenesis has been a major study topic in this model. The venous clip model is an intervention model for the chick embryo in which permanent obstruction of the right lateral vitelline vein temporarily reduces the mechanical load on the embryonic myocardium and induces a spectrum of outflow tract anomalies (3). This model was designed to obtain insight into the effects of altered venous return patterns on cardiac morphogenesis and malformations (4).

Immunolocalization of chick periostin protein in the developing heart

“…During cardiovascular development initially, periostin is expressed in response to signaling from the BMP and TGF-␤ family of growth factors (Horiuchi et al, 1999;Ji et al, 2000;Hall et al, 2001;Kruzynska-Frejtag et al, 2001Lindner et al, 2004). However, as development progresses, the heart must withstand the increasing influence of hemodynamic sheer stress (Stekelenburg et al, 2004). Thus, we might predict an increase of periostin within the valvular apparatus and the walls of the outflow tract, structures that also undergo tension and mechani- Fig.…”

Primary cilia sensitize endothelial cells for fluid shear stress

“…We showed that already during embryonic development, patterning of KLF2 gene expression relates to areas of high shear stress (Groenendijk et al, 2004;Vennemann et al, 2006). Experimental changes in embryonic blood flow lead to changes in gene expression patterning of KLF2, ET1, and eNOS (Groenendijk et al, 2005), and lead to loss of proper cardiovascular function (Stekelenburg-de Vos et al, 2005Ursem et al, 2004) and the development of structural anomalies (Hogers et al, 1997(Hogers et al, , 1999. We have recently identified the inverse correlation between the expression of KLF2 and the presence of endothelial primary cilia in the embryonic heart (Van der Heiden et al, 2006).…”

The Role of Shear Stress on ET-1, KLF2, and NOS-3 Expression in the Developing Cardiovascular System of Chicken Embryos in a Venous Ligation Model

“…Besides these morphological anomalies, hemodynamic defects have also been demonstrated, showing a decrease in heart rate and an increase in mean dorsal aortic blood flow (11). Hemodynamic changes occur immediately after venous clipping (124) but also have long-term effects, including increased ventricular stiffness due to reduced contractility and reduced compliance (123,135), as demonstrated with pulsed echo-Doppler analyses and videoscopically determined pressurevolume loops. The effects are demonstrated even extending to several days after the clip challenge (reviewed in Ref.…”