Cited 18 times since 2005 (1 per year) source: EuropePMC Basic research in cardiology, Volume 101, Issue 1, 11 2 2005, Pages 36-42 Suppression of physiological cardiomyocyte proliferation in the rat pup after neonatal glucocorticosteroid treatment. de Vries WB, Bal MP, Homoet-van der Kraak P, Kamphuis PJ, van der Leij FR, Baan J, Steendijk P, de Weger RA, van Bel F, van Oosterhout MF
Background
Glucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the present study we tested the hypothesis that a lower number of cardiomyocytes in later life is caused by a reduced cardiomyocyte proliferation and/or by early cell death (apoptosis).
Methods and results
Rat pups received dexamethasone or saline control on day 1, 2 and 3 and were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone treated pups showed a reduced proliferation as indicated by a lower mitotic index and reduced number of Ki-67 positive cardiomyocytes on day 2 and 4 as compared to day 0 and day 7 and also as compared to the age-matched saline pups. On day 7 and day 21 the mitotic index was not different between groups. From day 2 onward up to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase-3 and cleaved-PARP) in any group.
Conclusion
The temporary suppression of cardiomyocyte hyperplasia found in dexamethasone treated pups eventually leads to a reduced number and hypertrophy of cardiomyocytes during adult life.
