Dexamethasone (dex) is a synthetic glucocorticoid which improves pulmonary function in infants with bronchopulmonary dysplasia. Some infants experience adverse effects including myocardial hypertrophy. We have previously shown that rat pups given therapeutic daily doses of dex develop myocardial hypertrophy using both gross and biochemical measures of cardiac mass. This experiment was designed to study the in vivo histologic effects of dex on neonatal rat myocardium. Newborn Sprague-Dawley rats were randomly assigned to the treatment group (dex 0.125 mg/kg/day IP injection) while paired littermates receiving placebo served as controls. Daily body weight for each pup was recorded and the pups sacrificed after 7 days. The hearts were removed, weighed, and rinsed in 150mM NaCl followed by 1M KCl to relax the myocardium, prior to fixation in a 2% paraformaldehyde solution. A random sample of control and dex exposed hearts were embedded in paraflin and 3 μm cross-sections taken at the bi-ventricular level. Three sections from each heart, mounted and stained with hematoxylin and eosin for standard light microscopy were examined by a pathologist in a blinded study. Measurements of left ventricular(LV), right ventricular(RV), and septal thickness(SP) were taken at 10x magnification. The cross-sectional surface area(SA) of the sample was determined using the NIH Image Analyzer program. These values were normalized to heart weight(HW) for comparison. The number of myocyte nuclei per hpf (NN) taken at 100x magnification and the length of nuclei (NS) were determined. Groups were compared by t-test with all data presented as mean±SD (* denotes significance p<0.05). Table
RESULTS: Heart weight to body weight ratio, an indicator of myocardial hypertrophy, was elevated in the dex treated pups (0.004±0.001 vs. 0.0051±0.0006*) as seen in our previous work. There were fatty infiltrates evident in 42% of both control and dex treated hearts. The cross-sectional tissue surface area was not elevated despite elevation of LV thickness suggesting an obliteration of the LV cavity. We conclude that dexamethasone induces LV hypertrophy in the newborn Sprague-Dawley rat pup and that ventricular myocyte hyperplasia does not occur. (Partially funded by a grant from Wyeth Pharmaceuticals.)
