Histopathological changes of the heart after neonatal dexamethasone treatment: studies in 4-, 8-, and 50-week-old rats.
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.
Bal
Miriam P
MP
Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands.
de Vries
Willem B
WB
Steendijk
Paul
P
Homoet-van der Kraak
Petra
P
van der Leij
Feike R
FR
Baan
Jan
J
van Oosterhout
Matthijs F M
MF
van Bel
Frank
F
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001391:Azo Compounds; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004801:Eosine Yellowish-(YS); D006321:Heart / Q000187:drug effects*; D006416:Hematoxylin; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D010503:Periodic Acid-Schiff Reaction; D051381:Rats
D001391:Azo Compounds; C062246:Direct Red 81; D003907:Dexamethasone; D003094:Collagen; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin