Effect of increased pressure loading on heart growth in neonatal rats.

During embryonic and fetal development, the ventricular myocardium increases its mass principally by adding new cells (hyperplasia), while postnatally, it does so mainly through increase of cell size (hypertrophy). Switching between these two mechanisms of adaptation to increasing functional demand occurs in the early neonatal period. We investigated the response of the neonatal rat left ventricle to pressure overload induced by constriction of the abdominal aorta at postnatal day 2. Sampling for morphological examination with measurements of ventricular wall thickness and myocyte width was performed at days 2, 3, 5, 10, and 21. 3H-thymidine pre-labeling with label dilution was used to assess proliferative history at day 21, and bromodeoxyuridine labeling was used to measure the rates of DNA synthesis at each time point. The left ventricular wall was significantly thicker than in controls in the AC group from day 3, while thickness of individual myocytes was not increased until day 10. Label dilution showed evidence of higher number of cellular divisions correlating with severity of the phenotype in the AC group at day 21. Terminal DNA synthesis index was increased significantly at day 3, but there was no significant difference from controls at days 5, 10, or 21. Apoptotic rates were not different from controls at any sampling interval. Together, these results suggest that adaptation of the neonatal myocardium to increased pressure load is rapid, and is based on transitory hyperplasia followed by hypertrophy of myocytes.