Myocardial growth before and after birth: clinical implications*

Abstract

Perinatal changes in myocardial growth have recently evoked considerable interest with regard to cardiac chamber development with congenital cardiac lesions and to myocardial development in preterm infants. It is suggested that cardiac chamber development is influenced by blood flow. Experimental pulmonary stenosis in fetal lambs may induce either greatly reduced or markedly increased right ventricular volume. Ventricular enlargement appears to be associated with a large ventricular volume load resulting from tricuspid valve regurgitation. A small competent tricuspid valve is associated with reduced flow through the ventricle due to outflow obstruction and a small right ventricle. Postnatal growth of the ventricles in congenital heart disease is discussed. Increase in myocardial mass prenatally is achieved by hyperplasia, both during normal development and when myocardial mass is increased by right ventricular outflow obstruction. Postnatally, increases in myocardial mass with normal growth, as well as with ventricular outflow obstruction, are largely due to hypertrophy of myocytes. Myocardial capillary numbers do not increase in proportion with myocyte numbers in ventricular myocardium in association with outflow obstruction. The postnatal effects of these changes in congenital heart lesions are considered. Studies in fetal lambs suggest that the late gestational increase in blood cortisol concentrations is responsible for the change in the pattern of myocardial growth after birth. The concern is raised that prenatal exposure of the premature infant to glucocorticoids, administered to the mother to attempt to prevent hyaline membrane disease in the infant, may inhibit myocyte proliferation and result in a heart with fewer than normal myocytes. This would necessitate that each myocyte would have to hypertrophy abnormally to achieve a normal cardiac mass postnatally.

Reduced Life Expectancy in Rats After Neonatal Dexamethasone Treatment

“…Rudolph et al reported earlier that perinatal Dex treatment inhibits or even halts physiologic myocardial hyperplasia, leaving hypertrophy as the only possibility for the still undeveloped heart to grow (30). We indeed found myocardial hypertrophy and myocardial fibrosis in the neonatally Dex-treated adult rat at 11 mo of age together with a decreased number of cardiomyocytes (18), which originated from a direct effect of neonatal Dex administration (17).…”

Effect of Maternal Protein Restriction in Rats on Cardiac Fibrosis and Capillarization in Adulthood

“…Interestingly in a recent study in our laboratory, we found that maternal protein restriction throughout pregnancy in rats leads to a reduced heart size and a concomitant decrease in the number of cardiomyocytes (5). Because cardiomyocytes in general cease proliferating soon after birth, with postnatal growth of the heart predominantly due to cardiomyocyte hypertrophy (6), these findings could have important adverse implications on the structure and function of the heart later in life. We postulate that a decrease in the total number of cardiomyocytes in neonatal hearts will limit the capacity for physiologic cardiac growth in adulthood.…”

Effect of Maternal Protein Restriction During Pregnancy and Lactation on the Number of Cardiomyocytes in the Postproliferative Weanling Rat Heart

“…In humans, the proliferative capacity of cardiomyocytes is markedly decreased toward late gestation when the cardiomyocytes become terminally differentiated; this is characterized by myofibril assembly, sarcomeric formation and enhanced cellular contractility (Sadoshima and Izumo, 1997). Subsequent postnatal growth of the myocardium occurs by cardiomyocyte hypertrophy and/or deposition of extracellular matrix (Rudolph, 2000). In the rat heart, most cardiomyocytes are still proliferating at birth; the majority of the cardiomyocytes undergo the maturational switch during the first 2 weeks postnatally at which time they cease dividing (Li et al, 1996).…”