Neonatal Rabbit Model for Pressure-Overloaded Heart Failure and Preliminary Exploration of Mechanism.

Abstract

This study aimed to establish a model of pediatric heart failure (PHF) with concomitant left ventricle pressure overload by transverse aortic constriction (TAC) and study the PHF mechanism primarily at the gene transcription level. Twenty-four neonatal rabbits within 7 days after birth were randomly divided into sham (n = 8), moderate TAC (50% constriction, n = 8) and severe TAC (sTAC; 75% constriction, n = 8) groups. After the procedure transthoracic echocardiography was performed at 2, 4, and 6 weeks to measure left ventricle structure and function. Histologic staining and gene sequencing of left ventricle myocardial tissue were performed at 6 weeks. Six weeks after procedure transthoracic echocardiography showed that the pressure at the ligation of the aorta was 12.13 ± 0.95 mm Hg in the sTAC group, which was 26 times more than that of the sham group (P < .05), and left ventricular dilatation began to appear in the sTAC group. Gene sequencing showed significantly different microRNA expression between the sTAC and sham groups. Bioinformatics analysis among the 3 groups showed that the expression of ocu-miR-411-5p, ocu-miR-214-3p, and ocu-miR-432-5p was decreased in the sTAC group compared with the sham group (P < .05) and that the focal adhesion, insulin, and PI3K-Akt signaling pathways were also affected. Aortic constriction of 75% was optimal for the establishment of the PHF model. The expression of ocu-miR-411-5p, ocu-miR-214-3p, and ocu-miR-432-5p was significantly decreased, and the focal adhesion, insulin, and PI3K/AKT pathways may play significant roles in PHF progression.