Systolic and diastolic ventricular function in the normal and extra‐embryonic venous clipped chicken embryo of stage 24: a pressure–volume loop assessment

Abstract

Fluid mechanical forces affect cardiac development. In the chicken embryo, permanent obstruction of the right lateral vitelline vein by clipping reduces the mechanical load on the embryonic myocardium, which has been shown to induce a spectrum of outflow tract anomalies. Insight into the effects of this intervention on the mechanical function of the developing myocardium could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. We aimed to explore the effects of clipping on intrinsic systolic and diastolic ventricular function at stage 24 in the chicken embryo Cardiac pressure-volume relationships enable load-independent quantification of intrinsic ventricular systolic and diastolic properties. We determined ventricular function by pressure-volume loop analysis of in-ovo stage-24 chicken embryos (n = 15) 2 days after venous obstruction at 2.5 days of incubation (stage 17, venous clipped embryos). Control embryos (n = 15) were used for comparison. End-systolic volume was significantly higher in clipped embryos (0.36 +/- 0.02 microL vs. 0.29 +/- 0.02 microL, P = 0.002). End-systolic and end-diastolic pressure were also increased compared with control animals (2.93 +/- 0.07 mmHg vs. 2.70 +/- 0.08 mmHg, P = 0.036 and 1.15 +/- 0.06 mmHg vs. 0.82 +/- 0.05 mmHg, P < 0.001, respectively). No significant differences were demonstrated for other baseline hemodynamic parameters. Analysis of pressure-volume relationships showed a significantly lower end-systolic elastance in the clipped embryos (slope of end-systolic pressure-volume relationship: 2.91 +/- 0.24 mmHg/microL vs. 7.53 +/- 0.66 mmHg/microL, P < 0.005) indicating reduced contractility. Diastolic stiffness was significantly increased in the clipped embryos (slope of end-diastolic pressure-volume relationship: 1.54 +/- 0.21 vs. 0.60 +/- 0.08, P < 0.005), indicating reduced compliance. Venous obstruction apparently interferes with normal myocardial development, resulting in impaired intrinsic systolic and diastolic ventricular function. These changes in ventricular function may precede morphological derangements observed in later developmental stages.