Wb de Vries

Alterations in adult rat heart after neonatal dexamethasone therapy

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 μg/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.

Suppression of physiological cardiomyocyte proliferation in the rat pup after neonatal glucocorticosteroid treatment

AbstractBackgroundGlucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the present study we tested the hypothesis that a lower number of cardiomyocytes in later life is caused by a reduced cardiomyocyte proliferation and/or by early cell death (apoptosis).Methods and resultsRat pups received dexamethasone or saline control on day 1, 2 and 3 and were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone treated pups showed a reduced proliferation as indicated by a lower mitotic index and reduced number of Ki–67 positive cardiomyocytes on day 2 and 4 as compared to day 0 and day 7 and also as compared to the age–matched saline pups. On day 7 and day 21 the mitotic index was not different between groups. From day 2 onward up to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase–3 and cleaved–PARP) in any group.ConclusionThe temporary suppression of cardiomyocyte hyperplasia found in dexamethasone treated pups eventually leads to a reduced number and hypertrophy of cardiomyocytes during adult life.

Cardiac Biomarkers as Indicators of Hemodynamic Adaptation during Postasphyxial Hypothermia Treatment

Background: Little is known about the effects of hypothermia on the cardiovascular system in term newborns with neonatal encephalopathy. Objectives: To evaluate whether mild hypothermia for neonatal encephalopathy is cardioprotective as indicated by the cardiac biomarkers cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP). Methods: This was an observational cohort study of infants treated for perinatal asphyxia. In infants, mild total body hypothermia treatment of 33.5°C during 72 h was initiated (n = 20). Samples of cTnI and BNP were collected before the start of hypothermia, at 24 and 48 h after birth, and after rewarming (84 h). BNP and cTnI values were then compared with BNP and cTnI values of asphyxiated infants not treated with hypothermia (n = 28). Results: No differences were found between the groups in clinical patient characteristics or inotropic support. The hypothermia-treated patients seemed to be clinically more affected (5-min Apgar score, p < 0.05; umbilical artery pH, p = 0.08), but showed similar encephalopathy scores. Significantly lower values for BNP were found in hypothermia- compared to nonhypothermia-treated infants at 48 h and at normothermia after rewarming [144 pmol/l (95–286) vs. 75 pmol/l (45–143), 182 pmol/l (73–341) vs. 43 pmol/l (24–163)]. No differences were found for cTnI concentrations between both groups. Conclusions: The raised, but similar, cTnI values between hypothermia- and nonhypothermia-treated infants indicate similar myocardial damage in both groups. The lower BNP levels during hypothermia treatment suggest that hypothermia after perinatal asphyxia exerts a beneficial effect on cardiac function.

788 Fetal Hypoxia-Ischemia is Related to Circulatory Compromise in Preterm Infants

Background and Aims Impairment of gas exchange and blood flow through the placenta leads to hypoxia and hypercapnia. This causes increased systemic vascular resistance and tachycardia, thus compromising the cardiovascular system of the foetus. The biomarker B-type natriuretic peptide (BNP) can be used to identify significant cardiovascular compromise in infants. The aim of the present study was to investigate whether BNP can be used to identify those preterm infants with significant cardiovascular compromise during peripartum period. Methods In this retrospective cohort study all infants born after a gestational age of less than 32 weeks were evaluated. Maternal, fetal and infant factors associated with prenatal and perinatal hypoxia-ischemia were related to BNP levels after birth. Pathologic examination of the placenta was routinely performed. Results In total 164 infants were evaluated. Infants with increased placental ischemia and a higher placental maturation score had elevated levels of BNP at birth (r² 0.12; p<0.001). Furthermore BNP was found to be associated with (chronic) prenatal hypoxia-ischemia (nucleated red blood cells (r² 0.22; p<0.001); intrauterine growth retardation (r² 0.18; p<0.01); postnatal thrombocytopenia), and acute perinatal hypoxia (umbilical artery pH (r² 0.14; p<0.001); serum lactate (r² 0.11; p<0.001). Conclusion Elevated BNP levels after birth are found in those preterm infants with significant perinatal hypoxia-ischemia and are possibly related to placental dysfunction. If BNP levels are related to prenatal signs of circulatory compromise needs further investigation.

Placental Pathology is Related to Postnatal Circulatory Compromise in Preterm Infants

Background: Impairment of gas exchange and blood flow through the placenta leads to hypoxia and hypercapnia, causing increased systemic vascular resistance and tachycardia, influencing the cardiovascular system of the fetus. The biomarker B-type natriuretic peptide (BNP) can be used to identify significant cardiovascular disease in infants.Objective: To investigate whether placental pathology was associated with significant cardiovascular compromise in the premature infant as diagnosed by elevated BNP-levels after birth.Methods: From October 2009 until October 2010 134 infants born with GA< 32 weeks were evaluated. Placenta pathology was performed and related to BNP levels at admission, within 6 hours after birth.Results: Chorioamnionitis was present in 32%, signs of pathologic increased maturation in 55,2%. Increased placental maturation showed strong correlation with clinical diagnosis of pre-eclampsia (PE) (r=0.59,p< 0.001). BNP-levels were elevated in pregnancies complicated by clinical or pathological signs of PE (median 56 p/mol/l vs. 106 p/mol/L;p< 0.05). The highest BNP-levels were found in those infants where PE was complicated by fetal distress (91pmol/L vs. 390pmol/L;p< 0.01). The presence of chorioamnionitis was associated with lower BNP-levels, although this was not statistically significant (55 pmol/L vs. 94 pmol/L;p= 0.12) and possibly related to PE in the other group.Conclusion: This study shows that those infants, where maternal, pathological or clinical, PE was complicated by signs of fetal distress, are the most likely to have cardiovascular compromise at birth. Whether this is directly related to fetal cardiovascular adaptation to placental vascular pathology needs further investigation.

623 Does Early Spontaneous Closure of the Ductus Arteriosus in Very Preterm Infants Predict Final Closure|[quest]|

623 Does Early Spontaneous Closure of the Ductus Arteriosus in Very Preterm Infants Predict Final Closure?

142 B-Type Natriuretic Peptide as Early Biomarker for Evaluation of Persistent Pulmonary Hypertension Treatment in Neonates

142 B-Type Natriuretic Peptide as Early Biomarker for Evaluation of Persistent Pulmonary Hypertension Treatment in Neonates