Chronic modifications of lung and heart development in glucocorticoid-treated newborn rats exposed to hyperoxia or room air.
We assessed the mechanics and morphology of the lung in 165 rats treated neonatally with either room air (RA), O2, RA + steroids, or O2 + steroids. Newborn Sprague-Dawley male rats were randomly assigned to these groups. O2-exposure (0.96-1.0 FiO2) lasted 5 days, and dexamethasone treatment consisted of eight daily S.C. injections of drug or buffer in successive doses of 0.5, 0.4, 0.3, 0.2, 0.1, 0.1, 0.1, and 0.1 mg/kg. At 58 days, right ventricular systolic pressure (RVP) was measured. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighted right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alone did not, but steroid decreased survival rate to 79.4% (95.3% in RA rats, P < 0.02). Only 21 of 40 (52%) O2 + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O2 vs. RA rats. In RA + steroids rats, weight of the LV was decreased but RV, RVP, and lung vasculature were not affected. These effects were additive in the O2 + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O2 and steroids shifted the P-V curve to the left and O2 + steroids still further. Maximal lung volume increased significantly with RA + steroids and still further in O2 + steroids but not in O2 alone. O2 and steroids significantly increased the mean linear intercept and O2 + steroids even more so.(ABSTRACT TRUNCATED AT 250 WORDS)
Thibeault
D W
DW
University of Missouri-Kansas City School of Medicine, Mercy Hospital 64108-9898.
Heimes
B
B
Rezaiekhaligh
M
M
Mabry
S
S
D000388:Air; D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development*; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development*; D008176:Lung Volume Measurements; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003907:Dexamethasone; D010100:Oxygen