Alterations in adult rat heart after neonatal dexamethasone therapy.
Glucocorticoid treatment in preterm babies to prevent chronic lung disease causes myocardial hypertrophy and increased myocardial protein content. Although these changes are thought to be transient, there is evidence that dexamethasone (DEX) induces permanent myocardial abnormalities as well. We investigated whether a therapeutic course of neonatal DEX in rat pups produces anatomic and biochemical alterations in rat hearts during adult life. Twenty-four rat pups were treated with DEX on d 1, 2, and 3 (0.5, 0.3, and 0.1 micro g/g) of life, with doses proportional to those used in preterm babies. Twenty-four control pups were treated with saline. At d 7, wk 8, or wk 45 (n = 8 per group) rats were killed. The anatomic parameters measured were body weight (Bw, in grams), heart (myocardial) weight (Hw, in milligrams), and the Hw:Bw ratio. Myocardial total protein (Prot) and DNA content were determined, and the Prot:DNA ratio was calculated. Histopathology and morphometry were performed on 45-wk-old rat hearts. In DEX-treated rat pups, at d 7, Bw and Hw were lower and the Hw:Bw ratio was increased. DNA content was lower, Prot higher, and Prot:DNA ratio was increased. In 8-wk-old rats Bw, Hw, DNA content, Prot content or Prot:DNA ratio did not differ between groups, but the Prot:DNA ratio still tended to be higher in DEX-treated rats. In 45-wk-old rats Hw and Hw:Bw ratio were significantly lower and Prot:DNA ratio higher in DEX-treated rats. Histopathologic analysis showed larger cardiomyocyte volume, length, and width, indicating hypertrophy, and increased collagen, indicating early degeneration of individual myocytes. In conclusion, neonatal DEX treatment in rat pups causes a permanent decrease in heart weight, as well as hypertrophy and early degeneration of cardiomyocytes during adulthood.
de Vries
Willem B
WB
Department of Neonatology, University Medical Center/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
van der Leij
Feike R
FR
Bakker
Joost M
JM
Kamphuis
Patrick J G H
PJ
van Oosterhout
Matthijs F M
MF
Schipper
Marguerite E I
ME
Smid
Gioia B
GB
Bartelds
Beatrijs
B
van Bel
Frank
F
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D011506:Proteins; D003907:Dexamethasone; D004247:DNA