Growth and maturation of cardiac myocytes in fetal sheep in the second half of gestation

Abstract

Right (RVFW) and left (LVFW) ventricular free wall cardiac myocytes were collected from 25 fetal sheep aged 77-146 days gestation (term ϭ 150 days gestation), six salineinfused catheterized fetal sheep (129 GD), and five lambs to measure gestational changes in uni-and binucleated cardiac myocyte numbers and cell volumes by confocal microscopy. At 77 days gestation, 2% of the myocytes were binucleated, which increased to 50% at 135 days gestation and 90% at 4 -6 weeks after birth. RVFW uni-and binucleated myocytes were larger than those in the LVFW, and cell volumes of RVFW uni-and binucleated and LVFW binucleated myocytes (but not LVFW uninucleated myocytes) increased with gestation. Before birth, the approximate number of myocytes was greater in the LVFW than in the RVFW (P Ͻ 0.001). Before 110 GD, cardiac growth appeared to be due to myocyte hyperplasia, as approximate myocyte numbers and VFW weight increased at the same rate. After 110 days gestation, the approximate myocyte number/g VFW weight decreased, which suggests that myocyte hypertrophy, as well as hyperplasia, was occurring in association with the appearance of a greater proportion of binucleated cells after that time. By 4 -6 weeks of age, there was marked hypertrophy of myocytes and an apparent reduction in myocyte number. Anat Rec Part A 274A: 952-961, 2003.

Normal Reference Ranges from 11 to 41 Weeks’ Gestation of Fetal Left Modified Myocardial Performance Index by Conventional Doppler with the Use of Stringent Criteria for Delimitation of the Time Periods

“…In addition, the data are in line with neonatal studies reporting higher mean MPI values in term [38] compared to preterm [39] newborns. The pathophysiological basis of the increase in MPI values in late pregnancy could be associated with developmental changes in myocardium maturation [40] or it could be a nonspecific reflection of the more general hormonal changes occurring in fetal and placental physiology during the last weeks of gestation. Certainly this increase in MPI does not reflect a trend to be continued after birth because, interestingly, MPI values show a progressive reduction after birth [38].…”

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

“…The ventricle walls progressively thicken (Webb et al 1996, Christoffels et al 2000, driven predominantly by cardiomyocyte hyperplasia (Oparil et al 1984). As hyperplastic growth gives way to hypertrophic growth following birth, cardiomyocytes become binucleated, less spherical in shape and more rod-shaped allowing for more efficient mechanical and electrical coupling (Burrell et al 2003, Hirschy et al 2006. As these rod-shaped cardiomyocytes align with each other, the muscle fibres in the outermost layer of the compact myocardium form into spiraling bundles to create the typical architecture of the mature mammalian heart.…”

Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

“…In humans and large mammals, the heart grows entirely by cardiomyocyte proliferation during the first half of gestation (Smolich et al 1989, Austin et al 1995, Mayhew et al 1997. Thereafter, cardiomyocytes undergo terminal differentiation and binucleation at an increasing rate (Barbera et al 2000, Burrell et al 2003, so that some 80% of cardiomyocytes are binucleated at the time of birth. Evidence suggests that binucleated cardiomyocytes cannot divide (Clubb & Bishop 1984), these cells contribute to increased heart weight only by cellular hypertrophy (increased cell size), but not by hyperplasia.…”