| Objective: Glucocorticoid has been used to treat chronic lung disease inimmature babies. However, studies accumulated so far suggest that thistreatment could lead to some long-term negative effects, including cardiacalteration as cardiac hypertrophy, dilatation and cardiac fibrosis. In the presentstudy, we aim to explore the cardiac function after neonatal glucocorticoidtreatment and its susceptibility to ischemia/reperfusion injury in adult life.Methods: Pups were born naturally on day21-22of gestation. On theday of birth (day0) male pups were selected and randomly divided intotreatment or control groups fed by “foster mothers”(6pups per litter). Pups inthe treatment group were injected IP with dexamethasone (DEX) at day1,2and3(0.5,0.3and0.1g/g body weight, respectively) after birth in themorning from9:00to10:00. Controls were injected with equal volumes (10l/g) of saline (SAL). Rats were weaned at the3weeks of age and thenseparated from the foster mother at4weeks. Body weight was measuredregularly and the blood glucose level was measured at24weeks of age beforerats were sacrificed. Hearts were harvested. Alterations in ultrastructure wereobserved by Transmission electron microscopy (TEM)(n=3). Cardiac fluiddynamics (ischemia/reperfusion study) and myocardiac infarct size were alsoperformed at24weeks (n=10).All data were presented as mean±SD andP<0.05was considered statistically different.Results:1The effect of neonatal glucocorticoids treatment on growth, and heartweight, blood glucose level at24weeks of ageCompared with SAL-treated animal, neonatal glucocorticoids treatmentmay cause growth retardation which were found before10weeks of age (AllP<0.05except at3weeks). While catch-up growth was observed from12 weeks age onward.There were no differences of heart weight and heart/body ratio foundbetween SAL and DEX group at24weeks of age（Heart weight: DEX vs. SAL:1.43±0.17g vs.1.46±0.17g P>0.05）（Heart/body ratio: DEX vs. SAL:0.36±0.04%vs.0.35±0.04%P>0.05）. in addition, there was also nostatistical differences were found in blood glucose level at24weeks of agebetween control and experiment groups（Blood glucose: DEX vs. SAL:6.88±0.95mmol/L vs.6.85±0.78mmol/L P>0.05）2Cardiac ultrastructural alterations observed by TEMUnder TEM, structure of cardiomyocyte from SAL-treated rats was clearand its mitochondrial was intact. Neonatal DEX administration causeddisappearance of some ridge of the mitochondria in cardiomyocyte.3The effect of neonatal glucocorticoids treatment on the ability ofcardiac recovery after ischemia/reperfusion damageUnder the basal condition，there were no statistical differences found inLVDP,+LVdp/dtmax and-LVdp/dtmax between SAL and DEX groups (LVDP:DEX vs. SAL:132.7±12.3vs.131.4±27.1mmHg;+LVdp/dtmax: DEX vs.SAL:3262.1±96.3vs.3460.4±104.9mmHg;-LVdp/dtmax: DEX vs. SAL:-2001.9±111.2vs.-2244.7±95.3mmHg. P all>0.05)At60min of reperfusion，the recovery of LVDP,+LVdp/dtmax and-LVdp/dtmax were significantly lower in DEX-treated animals compared withSAL.(LVDP: DEX vs. SAL:31.7±8.4%vs.46.5±6.2%.+LVdp/dtmax: DEXvs. SAL:30.0±7.7%vs.42.8±5.3%.-LVdp/dtmax: DEX vs. SAL:24.9±6.1%vs.35.1±5.0%. P all <0.05)4The effect of neonatal glucocorticoids treatment on the size of cardiacinfarction after ischemia/reperfusionCompared with SAL-treated controls, neonatal DEX treatment seemedcause increased cardiac infarction size at24weeks of age after ischemia/reperfusion, however, this result didn’t reach statistical difference(DEX vs.SAL:25.8±1.1%vs.22.8±0.8%P>0.05). Conclusions：1Neonatal glucocorticoid treatment in rats may lead to growthretardation before12weeks. No reduced heart weight or relative heart weightwas found at24weeks of age after neonatal glucocorticodsi administration.2Neonatal glucocorticoid treatments may decrease the ability of recoveryduring ischemia/reperfusion. |
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