Circulating S100B and Adiponectin in Children Who Underwent Open Heart Surgery and Cardiopulmonary Bypass

Background. S100B protein, previously proposed as a consolidated marker of brain damage in congenital heart disease (CHD) newborns who underwent cardiac surgery and cardiopulmonary bypass (CPB), has been progressively abandoned due to S100B CNS extra-source such as adipose tissue. The present study investigated CHD newborns, if adipose tissue contributes significantly to S100B serum levels. Methods. We conducted a prospective study in 26 CHD infants, without preexisting neurological disorders, who underwent cardiac surgery and CPB in whom blood samples for S100B and adiponectin (ADN) measurement were drawn at five perioperative time-points. Results. S100B showed a significant increase from hospital admission up to 24 h after procedure reaching its maximum peak (P0.05) have been found all along perioperative monitoring. ADN/S100B ratio pattern was identical to S100B alone with the higher peak at the end of CPB and remained higher up to 24 h from surgery. Conclusions. The present study provides evidence that, in CHD infants, S100B protein is not affected by an extra-source adipose tissue release as suggested by no changes in circulating ADN concentrations

Mesenchymal stem/stromal cells—a key mediator for regeneration after perinatal morbidity?

Perinatal complications in both term- and preterm-born infants are a leading cause of neonatal morbidities and mortality. Infants face different challenges in the neonatal intensive care unit with long-term morbidities such as perinatal brain injury and bronchopulmonary dysplasia being particularly devastating. While advances in perinatal medicine have improved our understanding of the pathogenesis, effective therapies to prevent and/or reduce the severity of these disorders are still lacking. The potential of mesenchymal stem/stromal cell (MSC) therapy has emerged during the last two decades, and an increasing effort is conducted to address brain- and lung-related morbidities in neonates at risk. Various studies support the notion that MSCs have protective effects. MSCs are an easy source and may be readily available after birth in a clinical setting. MSCs' mechanisms of action are diverse, including migration and homing, release of growth factors and immunomodulation, and the potential to replace injured cells. Here, we review the pathophysiology of perinatally acquired brain and lung injuries and focus on MSCs as potential candidates for therapeutic strategies summarizing preclinical and clinical evidence

The development of lung biochemical monitoring can play a key role in the early prediction of bronchopulmonary dysplasia

AIM: Despite advances in perinatal management, there is a flat trend in incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. The main feature of BPD development in preterm infants is an imbalance between increased exposure to free radicals and inadequate antioxidant defences. We investigated the associations between BPD and lipid hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar lavage fluid (BALF). METHODS: In this prospective study, BALF samples were collected from 44 preterm infants with RDS and oxidative stress markers were measured in 11 with BPD and 33 controls without BPD. RESULTS: LOOH levels were significantly higher (p<0.01) in the BPD group (median 16.35; 25th -75th centile 13.75-17.05 nmol/mL) than in the no BPD group (median 13.18; 25th -75th centile 12.92-13.63 nmol/mL). Conversely, GSH levels were significantly lower in the BPD group (p<0.01) (median 11.52; 25th -75th centile 6.95-13.85 mumol/mg) than the no BPD group (median: 18.69; 25th -75th centile: 13.89-23.64 mumol/mg). Multiple regression analysis showed significant correlations between BPD and mechanical ventilation time (p<0.01) and LOOH levels (p<0.05). CONCLUSION: Early LOOH level increases in preterm infants developing BPD suggest that lung biochemical monitoring of sick infants might be possible and BPD could be predicted early by evaluating biomarkers. This article is protected by copyright. All rights reserved

Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth

Introduction: Perinatal asphyxia (PA) is a major cause of neonatal mortality and morbidity. Research has shown that in rats fetal asphyxia (FA) can provoke neuroprotection against a subsequent more severe perinatal asphyctic insult. This is called fetal asphyctic preconditioning (PC). Our objective was to investigate alterations in the placental inflammatory phenotype associated with PC. Methods: FA was induced in the rat at embryonic day 17 by reversibly clamping the uterine circulation and PA was induced at birth by submersion of the uterine horns in a saline bath for 19 min. The effect of PC was studied by inducing FA at E17, followed by PA at E21. Placental TNF-alpha, IL-1 beta, IL-6 and IL-10 mRNA and protein levels were measured by qPCR and ELISA. Results: IL-1 beta mRNA increased in the labouring FA group, but IL-10 protein decreased after both FA and PA. In the PC group, IL-113 mRNA and protein levels were similar to controls. IL-6 protein increased 6 h after FA, however decreased 24 h after FA. IL-6 mRNA was higher in the labouring PA group. IL-10 protein decreased 24 h after FA. At birth, IL-10 mRNA increased in the PA group; however, IL-10 protein decreased in both the PA and the FA group. In the PC group, IL-10 mRNA and protein were similar to control levels. Discussion: Depleted protein concentrations of IL-10 and IL-113 after one single asphyctic insult were reversed after fetal asphyctic PC. In addition, PC placentas showed less up-regulation of IL-6 mRNA compared to the PA ones. This modulated placental inflammatory phenotype might contribute to the improved neonatal outcome showed after fetal asphyctic PC

Perioperative GABA Blood Concentrations in Infants with Cyanotic and Non-Cyanotic Congenital Heart Diseases

Perioperative stress detection in children with congenital heart disease (CHD), particularly in the brain, is still limited. Among biomarkers, γ-amino-aminobutyric acid (GABA) assessment in biological fluids appears to be promising for its regulatory action on the cardiovascular and cerebral systems. We aimed to investigate cyanotic (C) or non-cyanotic (N) CHD children for GABA blood level changes in the perioperative period. We conducted an observational study in 68 CHD infants (C: n = 33; N: n = 35) who underwent perioperative clinical, standard laboratory and monitoring parameter recordings and GABA assessment. Blood samples were drawn at five predetermined time-points before, during and after surgery. No significant perioperative differences were observed between groups in clinical and laboratory parameters. In C, perioperative GABA levels were significantly lower than N. Arterial oxygen saturation and blood concentration significantly differed between C and N children and correlated at cardiopulmonary by-pass (CPB) time-point with GABA levels. The present data showing higher hypoxia/hyperoxia-mediated GABA concentrations in C children suggest that they are more prone to perioperative cardiovascular and brain stress/damage. The findings suggest the usefulness of further investigations to detect the “optimal” oxygen concentration target in order to avoid the side effects associated with re-oxygenation during CPB