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Effect of increased pressure loading on heart growth in neonatal rats
David Sedmera1, Robert P Thompson, Frantisek Kolar
1Institute of Physiology, University of Lausanne, Switzerland. sedmerad@musc.edu
Insights
Neonatal rat hearts adapt to pressure overload through rapid cell division (hyperplasia) followed by cell growth (hypertrophy). This study reveals the heart
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Neonatal Physiology
Background:
- Heart mass increases via cell division (hyperplasia) in development and cell size (hypertrophy) postnatally.
- The transition between hyperplasia and hypertrophy occurs in the early neonatal period.
- Understanding neonatal heart adaptation to stress is crucial for cardiovascular health.
Purpose of the Study:
- To investigate the neonatal rat left ventricle's response to pressure overload.
- To determine the mechanisms of cardiac adaptation (hyperplasia vs. hypertrophy) in early life.
- To analyze the timing and extent of cellular changes following induced pressure overload.
Main Methods:
- Induced pressure overload in neonatal rats via abdominal aorta constriction at postnatal day 2.
- Monitored ventricular wall thickness and myocyte width at multiple time points (days 2-21).
- Assessed cell proliferation using 3H-thymidine pre-labeling/dilution and bromodeoxyuridine labeling for DNA synthesis.
Main Results:
- Significantly increased left ventricular wall thickness observed from day 3 post-constriction.
- Myocyte thickness increased starting from day 10, indicating hypertrophy.
- Evidence of increased cellular divisions (hyperplasia) was noted by day 21, correlating with phenotype severity.
- Transient increase in DNA synthesis at day 3, with no significant differences later; apoptosis rates remained unchanged.
Conclusions:
- Neonatal myocardium adapts rapidly to pressure overload.
- Adaptation involves a transient phase of hyperplasia followed by myocyte hypertrophy.
- These findings highlight the dynamic nature of neonatal cardiac remodeling under stress.
Abstract:
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.