Alterations in adult rat heart after neonatal dexamethasone therapy

被引:74
作者
De Vries, WB
Van der Leij, FR
Bakker, JM
Kamphuis, PJGH
Van Oosterhout, MFM
Schipper, MEI
Smid, DB
Bartelds, B
Van Bel, F
机构
[1] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Dept Neonatol, NL-3508 AB Utrecht, Netherlands
[2] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Dept Pediat Immunol, NL-3508 AB Utrecht, Netherlands
[3] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Dept Pathol, NL-3508 AB Utrecht, Netherlands
[4] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Rudolf Magnus Inst Neurosci, NL-3508 AB Utrecht, Netherlands
[5] Univ Groningen, Beatrix Childrens Hosp, Inst Drug Explorat, Dept Pediat, Groningen, Netherlands
关键词
D O I
10.1203/01.PDR.0000036281.74804.27
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 mug/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.
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收藏
页码:900 / 906
页数:7
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