Histopathological Changes of the Heart After Neonatal Dexamethasone Treatment: Studies in 4-, 8-, and 50-Week-Old Rats

Bal, Miriam P; Vries, Willem B. de; Steendijk, Paul; Kraak, Petra Homoet-van der; Leij, Feike R. van der; Baan, Jan; Oosterhout, Matthijs F.M. van; Bel, Frank van

doi:10.1203/pdr.0b013e3181a283a0

Cited by 34 publications

(31 citation statements)

References 36 publications

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“…In addition, total body weight was lower in Dex-treated rats, which suggests that neonatal Dex treatment had a negative effect on organ growth and development. This was similar to findings in earlier studies (13)(14)(15). The differences in weight may be partially due to nutritional problems in the days after the neonatal treatment.…”

Section: Discussionsupporting

confidence: 91%

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Neonatal Dexamethasone Treatment in the Rat Leads to Kidney Damage in Adulthood

et al. 2010

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ABSTRACT:Recently, concern has been raised that corticosteroid treatment of preterm neonates might be associated with adverse effects later in life, including early development of hypertension. Here, we investigate the impact of neonatal dexamethasone (Dex) treatment on early renal cell proliferation and nephron number. We analyzed mitotic activity in renal cortex of rat pups neonatally treated with Dex. Nephron number was measured and possible renal damage was quantified by counting inflammatory foci, ED-1 positive cells (macrophages), and the desmin score (activated podocytes). Mitotic activity was 34 and 29% lower on d 2 and 4 in Dex-treated rats compared with saline-treated controls. The number of glomeruli was lower at 4 wk, but nephron size was unchanged after Dex treatment, as calculated from glomerular density and (lower) body-and kidney weight. At wk 50, the glomerular number was significantly lower in Dex-treated rats, whereas body and kidney weight were the same as in Sal controls. Dex rats also showed more kidney damage, manifested by a ϳ3.5-fold increase in inflammation foci/mm 2 and in ED-1 positive cells/mm 2 and a ϳ4.3-fold increased desmin score. Temporary suppression of mitotic activity during neonatal Dex treatment leads to reduction of nephron number and more kidney damage later in life. (Pediatr Res 67: 72-76, 2010)

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Section: Discussionsupporting

confidence: 91%

“…It was shown that in rats a 3-d course of Dex significantly suppressed proliferative activity of cardiomyocytes in the first week of life. At 50 wk of age this resulted in a lower number of cardiomyocytes in the heart, cardiomyocyte hypertrophy and increased interstitial fibrosis (13)(14)(15).…”

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Neonatal Dexamethasone Treatment in the Rat Leads to Kidney Damage in Adulthood

et al. 2010

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“…Our results indicated that DEX-treated rats had significantly lower body weights than SAL-treated rats up to 14 wk of age, and no reduced body weight mentioned afterwards, indicating neonatal DEX administration may cause transient growth retardation, and there might exit a catch-up body weight gain in adult life. Previous studies described lower heart weights in rats aged 50 wk following neonatal DEX administration (12). However, in the present experiment, no alterations in relative Figure 6.…”

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confidence: 56%

Effects of neonatal dexamethasone administration on cardiac recovery ability under ischemia-reperfusion in 24-wk-old rats

Jiang

et al. 2016

Pediatr Res

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Background: Evaluations of stress-induced cardiac functional alterations in adults after neonatal glucocorticoid (GC) treatment have been limited. In the present study, we evaluated adult cardiac functional recovery during postischemic reperfusion and measured cardiac gene expression involved energy metabolism in rats neonatally treated with dexamethasone (DEX). Method: Male Wistar rats were injected DEX in first 3 d after birth and controls were received saline (SAL). At 24 wk of age, insulin tolerance tests were performed, plasma lipid levels were measured, and left ventricular function and myocardial infarct size were evaluated. Expressions of genes involved in cardiac energy metabolism were measured by quantitative real-time polymerase chain reaction (PCR) and western blot. results: In 24-wk-old rats, neonatal DEX administration caused dyslipidemia, impaired cardiac recovery function and increased size of infarction, decreased cardiac expression of glucose transporter 4(GLUT4), peroxisome proliferative-activated receptor gamma coactivator 1α (PGC-1α) and ratios of phospho-forkhead box O1/forkhead box O1 (p-FoxO1/FoxO1) and phospho AMP-activated protein kinase/AMP-activated protein kinase (p-AMPK/AMPK) but increased pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) expression compared with controls. conclusion: Neonatal DEX administration impairs cardiac functional recovery during reperfusion following ischemia in 24-wk-old rats. Reduced cardiac glucose utilization may contribute to the long-term detrimental effects caused by neonatal DEX treatment.

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“…Increase in heart size during the fetal and early postnatal period occurs mainly by hyperplasia of cardiomyocytes [17] while later it is mainly due to cell hypertrophy [18]. Cardiomyocyte hyperplasia during the perinatal period may be impaired by various nutritional, hemodynamic and humoral factors [19], which are more common in ELBW children. A recent study showed that resuscitation with 100% oxygen compared to room air led to the increase of myocardial damage in an animal model [20].…”

Section: Discussionmentioning

confidence: 99%

From a Regional Cohort of Extremely Low Birth Weight Infants: Cardiac Function at the Age of 7 Years

et al. 2013

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Background: The long-term impact of prematurity on cardiac structure and function has not yet been fully discovered. Objectives: To assess long-term cardiac complications in the regional cohort of extremely low birth weight (ELBW) children born in 2002-2004. Material and Methods: Eighty-one children born as ELBW infants (91% of the available cohort) with a median birth weight of 890 g (25-75th percentile: 760-950) were evaluated at the mean age of 6.7 years. The control group included 40 children born full-term, selected from one general practice in the district. Echocardiography and 24-hour ambulatory blood pressure measurements (ABPM) were performed. The primary outcome variable was the presence of cardiac complications such as left ventricular hypertrophy (LVH), diastolic dysfunction or systolic dysfunction. Results: LVH was diagnosed in 4/81 ELBW children and 2/40 control children (p = 1.0). Concentric remodeling was detected in 8 (10%) subjects from the ELBW group and in 2 (5%) from the control group (p = 0.49). There were no patients with diastolic or systolic dysfunction in either group. After having expressed the results of M-mode echocardiography as z-scores for body surface area (BSA), statistically significant differences were observed for right-ventricle dimension in diastole (-1.49 ± 1.25 vs. -0.31 ± 0.91; p < 0.001), LV inner dimension in diastole (-0.53 ± 1.26 vs. 0.13 ± 0.94; p = 0.01) and left atrium (-0.93 ± 1.07 vs. -0.15 ± 1.02; p < 0.01). Heart rate (HR) was significantly faster in ELBW children (92.9 ± 8.4 vs. 86.7 ± 7.4 bpm; p = 0.01 adjusted for BSA) and they also had significantly higher night-time blood pressure [mean (z-score): 1.15 vs. 0.2; p = 0.02] without nocturnal dipping (night-time dipping <10%: 13 (16.7%) vs. 2 (5.2%), p = 0.13). Conclusions: No differences were found between the groups in the occurrence of cardiac complications. Ex-preterm ELBW children at age 6 may have a faster HR, smaller cardiac dimensions on echocardiography and higher nocturnal blood pressure. The clinical relevance of these findings is unknown.

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Histopathological Changes of the Heart After Neonatal Dexamethasone Treatment: Studies in 4-, 8-, and 50-Week-Old Rats

Cited by 34 publications

References 36 publications

Neonatal Dexamethasone Treatment in the Rat Leads to Kidney Damage in Adulthood

Neonatal Dexamethasone Treatment in the Rat Leads to Kidney Damage in Adulthood

Effects of neonatal dexamethasone administration on cardiac recovery ability under ischemia-reperfusion in 24-wk-old rats

From a Regional Cohort of Extremely Low Birth Weight Infants: Cardiac Function at the Age of 7 Years

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