Related Experiment Video
Updated: Jun 24, 2026
A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats
Published on: March 1, 2022
Histopathological changes of the heart after neonatal dexamethasone treatment: studies in 4-, 8-, and 50-week-old
Miriam P Bal1, Willem B de Vries, Paul Steendijk
1Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Neonatal dexamethasone (Dex) treatment in rats led to increased heart cell size and collagen. This suggests potential long-term cardiovascular risks in infants receiving this treatment.
Area of Science:
- Cardiovascular Science
- Neonatal Medicine
- Histopathology
Background:
- Dexamethasone (Dex) is used to prevent chronic lung disease in preterm infants.
- Long-term cardiovascular effects of neonatal Dex are not well-studied.
- Previous rat studies indicated potential cardiac issues and premature death.
Purpose of the Study:
- To investigate long-term histopathological myocardial changes in rats following neonatal Dex administration.
- To assess the impact of neonatal Dex on heart growth, cardiomyocyte structure, and cardiac fibrosis.
Main Methods:
- Rat pups received neonatal Dex or saline (control) on days 1-3.
- Heart tissue was analyzed at 4, 8, and 50 weeks post-birth.
- Histological staining (H&E, PAS, Sirius Red) evaluated cardiomyocyte morphometry, collagen, macrophages, and mast cells.
Main Results:
- Dexamethasone-treated rats showed increased cardiomyocyte length and volume (hypertrophy at 50 wk).
- Ventricular weight was reduced in Dex-treated rats.
- Collagen content significantly increased with age, being 62% higher in adult Dex rats.
- Increased macrophage and mast cell presence was observed in Dex-treated hearts.
Conclusions:
- Neonatal Dex negatively impacts normal heart development, leading to cardiomyocyte hypertrophy and increased collagen deposition in adult rat hearts.
- These findings suggest potential long-term cardiovascular risks associated with neonatal glucocorticoid therapy.
- Cardiovascular monitoring of preterm infants treated with glucocorticoids is recommended.
Abstract:
Dexamethasone (Dex), for prevention of chronic lung disease in preterm infants, showed potential negative long-term effects. Studies regarding long-term cardiovascular effects are lacking. We investigated possible histopathological myocardial changes after neonatal Dex in the young and adult rat heart. Rats were treated with Dex on d 1, 2, and 3 (0.5, 0.3, and 0.1 mg/kg) of life. Control-pups received saline. At 4, 8, and 50 wk after birth rats were killed and anatomic data collected. Heart tissue was stained with hematoxylin and eosin, Cadherin-periodic acid schiff, and sirius red for cardiomyocyte morphometry and collagen determination. Presence of macrophages and mast cells was analyzed. Cardiomyocyte length of the Dex-treated rats was increased in all three age groups, whereas ventricular weight was reduced. Cardiomyocyte volumes were increased at 50 wk indicating cellular hypertrophy. Collagen content gradually increased with age and was 62% higher in Dex rats at 50 wk. Macrophage focus score and mast cell count were also higher. Neonatal Dex affects normal heart growth resulting in cellular hypertrophy and increased collagen deposition in the adult rat heart. Because previous studies in rats showed premature death, suggesting cardiac failure, cardiovascular follow-up of preterm infants treated with glucocorticoids should be considered.
