Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0-1025.5/10(6) cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.

Automated summary

Children with tetralogy of Fallot (TF) experience hemodynamic overload and hypoxemia after birth. Comparative analysis showed significant increase in ploidy and morphology of right ventricular cardiomyocytes in these children. Connexin43-containing gap junctions were predominantly distributed diffusely over the cardiomyocytes sarcolemma and redistributed into intercalated discs during cardiomyocyte differentiation. The number of Ki67-positive cardiomyocytes varied greatly and decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity were observed in cardiomyocytes of children with TF. The proportion of interstitial tissue did not differ significantly from the control group. Myocardium in children with TF under six months of age was most sensitive to hypoxemia, resulting in delayed intercalated discs and myofibril assembly, and dystrophic changes in cardiomyocytes. The adaptation to hemodynamic overload and hypoxemia in immature myocardium of TF children involved the acceleration of ontogenetic growth and differentiation of cardiomyocytes, rather than reactivation of their proliferation.