The Influence of Naturally Occurring Differences in Birthweight on Ventricular Cardiomyocyte Number in Sheep

Abstract

In most species including man, cardiomyocytes cease proliferating soon after birth when they become terminally differentiated. A reduced complement of cardiomyocytes in infancy may adversely impact on the function and adaptive capabilities of the heart in later life. Low birthweight is associated with an increased risk of heart disease in adults, but little is known about its effect on the number of cardiomyocytes. Using naturally occurring differences in birthweight, our aim was to determine the effect of birthweight on cardiomyocyte number in postnatal lambs. At 9 weeks after term birth, when the final number of cardiomyocytes is considered to be established, hearts were collected at necropsy from seven singleton and seven twin lambs. Hearts were perfusion-fixed, and tissue samples were systematically taken from the left ventricle plus intraventricular septum (LV+S) and the right ventricle (RV). The number of cardiomyocyte nuclei was estimated using an unbiased optical disector-fractionator stereological technique, and the total number of cardiomyocytes was determined. Weights of the total heart, LV+S and RV were significantly related to both birthweight and necropsy weight. In the LV+S but not the RV, cardiomyocyte number was significantly and directly related to heart tissue weight, birthweight, and necropsy weight. We conclude that the final number of cardiomyocytes in the LV+S is related to prenatal and early postnatal growth, and is proportionate to the weight of heart tissue. A low cardiomyocyte number in the LV+S following restricted fetal growth may contribute to the increased incidence of heart disease in adults born with low birthweight. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.