165 - Ventricular geometry maintains normal radius of curvature and wall thickness in a novel hypoplastic left heart model in fetal sheep.

Poster Number: 165
Publication Number: 165.2765

Background: Development of intracardiac anatomy in utero is dependent on flow dynamics through the heart during critical developmental stages. Left sided obstructive lesions can cause maldevelopment of the left ventricle, leading to a spectrum of congenital conditions from mild obstruction to hypoplastic left heart syndrome and associated single ventricle physiology. Using a fetal lamb model of left ventricle (LV) inflow obstruction, our lab has shown a reduction in LV chamber volume on echocardiography by two thirds (p=0.03) and a trend toward increased right ventricular (RV) chamber area (p=0.07). Post mortem, LV free wall weights were 23% smaller (p=0.02) with an associated 25% decrease in the LV:RV weight ratio (p < 0.01).

Objective: Evaluate left and right ventricular geometry in a late gestation fetal sheep model of LV inflow obstruction in comparison to age-matched sham controls.

Design/Methods: 7 experimental (Exp) and 9 sham fetuses were instrumented at 120 days gestational age (dGA; term=147d). Arterial, venous, and amniotic catheters; an ascending aortic flow probe; and a deflated left atrial balloon were placed. Balloons in Exp fetuses were inflated over the 8d study until aortic flow was eliminated; balloons remained deflated in instrumented shams. On study day 8 (134 dGA), fetal hearts were arrested in diastole with saturated potassium chloride, excised, then perfusion fixed (27 cmH20, 4% paraformaldehyde). Whole fixed hearts were stored in paraformaldehyde for 18-24 hours, then transected at the level of the papillary muscles. Sections were scanned using a flatbed scanner. Scanned images were used with commercial imaging software to evaluate ventricular geometry, including radius of curvature, ventricular free wall thickness, and septal thickness. Both halves of each heart were measured and averaged prior to statistical evaluation.

Results: The radius of curvature of the LV was similar between Exp and sham groups (p=0.33), as was the radius of curvature of the RV (p=0.81). LV (p=0.88) and RV (p=0.94) wall thickness were not different in the study group compared to the sham group. Septal thickness was also similar in the study group compared to the sham group (p=0.47).

Conclusion(s): In a novel fetal sheep model of hypoplastic LV, no differences in ventricular geometry were detected in comparison to sham animals despite findings of decreased weight of the LV, decreased LV to RV weight ratio, and decreased LV volume under abnormal loading conditions. This finding may represent plasticity of the fetal heart, with the ability to maintain normal geometry under the stress of late term LV inflow obstruction.