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Eduardo Bancalari

Publications and source records attributed to Eduardo Bancalari.

At least 19 recordsLinked to original sources
PubMed2006

ALK-5 mediates endogenous and TGF-beta1-induced expression of connective tissue growth factor in embryonic lung.

Transforming growth factor-beta1 (TGF-beta1) has been implicated as a major negative regulator of lung branching morphogenesis. Since connective tissue growth factor (CTGF) is a downstream mediator of TGF-beta1 effects on mesenchymal cells, we hypothesized that TGF-beta1 induces CTGF expression in mouse embryonic lung explants and that CTGF mediates TGF-beta1 inhibition of branching morphogenesis. We show that addition of TGF-beta1 to the serum-free medium of embryonic day (E)12.5 lung explant cultures inhibited branching morphogenesis and induced CTGF mRNA expression in time- and dose-dependent manners. In contrast to basal endogenous CTGF protein, which was exclusively localized in the distal airway epithelium, TGF-beta1-induced CTGF protein was localized in both the epithelium and the mesenchyme. Addition of exogenous CTGF to culture medium directly inhibited branching morphogenesis. To identify the signal transduction pathway through which TGF-beta1 induces CTGF, we used SB431542, a specific inhibitor for TGF-beta type I receptor (TbetaRI)/ALK-5 to block TGF-beta1-induced Smad2/3 phosphorylation. Consequently, SB431542 stimulated normal branching morphogenesis and blocked TGF-beta1 inhibition of branching. Furthermore, SB-431542 blocked both endogenous and TGF-beta1-induced expression of CTGF mRNA and protein. These results demonstrate for the first time that TGF-beta1 induces CTGF expression in mouse embryonic lung explants, that CTGF inhibits branching morphogenesis, and that both endogenous and TGF-beta1-induced CTGF expression are mediated by the TbetaRI/ALK-5-dependent Smad2 signaling pathway.

Activin Receptors, Type I↗
PubMed2006

Acute effects of PEEP on tidal volume and respiratory center output during synchronized ventilation in preterm infants.

BACKGROUND: Positive end expiratory pressure (PEEP) is routinely used in mechanically ventilated preterm infants to maintain lung volume. An acute increase in PEEP can affect lung mechanics and tidal volume, but it is unknown if these effects elicit compensatory changes in respiratory center output. OBJECTIVES: To investigate the acute effects of changes in PEEP on tidal volume (V(T)), lung compliance (C(L)), and respiratory center output (RCO) during synchronized intermittent mandatory ventilation (SIMV) in preterm infants at different levels of basal respiratory drive. METHODS: Preterm infants were studied during SIMV at three levels of PEEP (2, 4, and 6 cm H(2)O for 2-3 min each) and at two levels of inspired CO(2). Peak inspiratory pressure (PIP) was adjusted to maintain the same delta pressure at the airway. RCO was assessed by measuring total diaphragmatic electrical activity. The level of inspired CO(2) was adjusted by modifying the instrumental dead space. RESULTS: Sixteen preterm infants GA: 25 +/- 2 weeks, BW: 786 +/- 242 g, age: 18 +/- 15 days, SIMV: rate 14 +/- 3 b/min, Ti: 0.35 +/- 0.01 s, PIP: 16 +/- 1 cm H(2)O, and FiO(2): 0.31 +/- 0.06 were studied. At both levels of inspired CO(2), C(L), V(T), and V'(E) from spontaneous and mechanical breaths decreased significantly with higher PEEP. RCO did not change, but at lower respiratory drive, there was a trend towards an increase in RCO with higher PEEP. CONCLUSION: Higher PEEP levels can have acute negative effects on lung mechanics and ventilation in preterm infants without a sufficient compensatory increase in RCO.

Humans↗
PubMed2006

Definitions and diagnostic criteria for bronchopulmonary dysplasia.

The changes in clinical presentation of bronchopulmonary dysplasia (BPD) in recent years have made many of the original definitions of BPD obsolete. The use of supplemental oxygen as a criterion for BPD diagnosis has many limitations. Supplemental oxygen is necessary to treat these infants, but at the same time it plays an important role in the pathogenesis of BPD. Because there are no accepted standards for supplemental oxygen administration, there are wide variations for its indications among different centers and this has a marked effect on the reported incidence of BPD. For this reason, it is essential to standardize the indications for supplemental oxygen when duration of oxygen therapy is used as the main criteria to diagnose BPD. Using supplemental oxygen need at specific time points does not necessarily reflect chronic lung damage and should be avoided as a single diagnostic criterion for BPD. A prolonged duration of supplemental oxygen is necessary to demonstrate the presence of chronic lung damage. The criteria based on supplemental oxygen at 36 weeks postmenstrual age has gained wide acceptance, but it is a less stringent criterion for the more mature infants. The longer the gestation, the shorter the time on oxygen that is required to meet this BPD criterion. None of the proposed criteria based on duration of oxygen therapy have shown a strong predictive value for long-term outcome. In view of all these shortcomings, it is essential to develop more objective physiologic tools to define the degree of lung damage and improve the prediction for long-term outcome in these infants.

Bronchopulmonary Dysplasia↗
PubMed2006

Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants.

BACKGROUND: Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning. OBJECTIVE: The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure. METHODS: Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death. RESULTS: There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency. CONCLUSIONS: The results of this study suggest that the addition of pressure support as a supplement to synchronized intermittent mandatory ventilation during the first 28 days may play a role in reducing the duration of mechanical ventilation in extremely low birth-weight infants, and it may lead to a reduced oxygen dependency in the 700- to 1000-g birth weight strata.

Female↗
PubMed2005

Effects of volume-targeted synchronized intermittent mandatory ventilation on spontaneous episodes of hypoxemia in preterm infants.

BACKGROUND: Hypoxemic episodes in ventilated preterm infants are frequently caused by reduced ventilation due to a decrease in lung volume and acute worsening of respiratory mechanics. OBJECTIVE: To compare the efficacy of conventional time-cycled, pressure-limited flow synchronized intermittent mandatory ventilation (SIMV) and volume-targeted SIMV (VT-SIMV) in reducing the frequency and severity of these episodes. METHODS: SIMV and VT-SIMV were compared in preterm infants with frequent spontaneous episodes of hypoxemia. VT-SIMV was provided with the Draeger Babylog 8000plus ventilator in volume-guarantee mode. RESULTS: In all, 32 infants (birth weight 668 +/- 126 g, gestational age 24.8 +/- 1.1 weeks, age 37.5 +/- 17.3 days) were studied during 2-hour periods of SIMV and VT-SIMV in random sequence. In an initial phase, a group of 12 infants was supported during VT-SIMV with a target tidal volume of 4.5 ml/kg (VT-SIMV 4.5). A planned interim analysis did not show differences in frequency and duration of hypoxemia between VT-SIMV 4.5 and SIMV, and the initial phase was stopped. In a second phase of the study, 20 infants were studied while supported with a target tidal volume of 6.0 ml/kg during VT-SIMV (VT-SIMV 6.0). In the second phase of the study, the frequency of the hypoxemic episodes did not change but the mean episode duration was shorter during VT-SIMV compared to SIMV. The proportion of mechanical breaths with small tidal volumes (< or =3 ml/kg) was reduced during VT-SIMV 6.0 versus SIMV, while the peak inspiratory pressure and mean airway pressure were increased. CONCLUSION: VT-SIMV did not reduce the frequency of hypoxemic episodes, but VT-SIMV 6.0 was effective in reducing the duration of the hypoxemic episodes.

Gestational Age↗
PubMed2005

Nonimmune hydrops fetalis in the liveborn: series of 32 autopsies.

Nonimmune hydrops fetalis (NIHF) or generalized soft tissue edema and cavity effusions may be due to cardiovascular diseases, congenital infections, genitourinary malformations, thoracic masses, placental conditions, chromosomal abnormalities, and idiopathic. We report 32 cases of NIHF from among 429 neonates who underwent autopsies (incidence 7.45%). Sixteen cases (50%) had cardiovascular disease; all were due to low output cardiac failure; 7 had structural congenital heart disease. Three of the children with congenital heart disease also had chromosomal abnormalities: 2 had trisomy 18 and 1 had Noonan syndrome. Among myocardial conditions were five subjects with cardiomyopathies (1 of each of the following types): oncocytic, dilated, endocardial fibroelastosis, cardiac glycogenosis, and carnitine deficiency; 3 had myocarditis, and 1 had cardiac rhabdomyomas. Congenital infections were due to cytomegalovirus in 3 cases, bacteria in 2, and parvovirus in 1. The mechanism of NIHF in these cases might be a combination of decreased myocardial contractility due to myocarditis and fetal anemia. Genitourinary diseases were present in 5 newborns: Two had congenital nephrotic syndrome, 1 had VACTER association, 1 had prune-belly syndrome, and 1 had urogenital sinus malformation. Intrathoracic lesions were found in 2 babies (pulmonary sequestration and diaphragmatic hernia). One twin died of volume overload due to twin transfusion syndrome. Only 2 newborns were classified as idiopathic. Our study shows that cardiovascular diseases that lead to heart failure or impaired venous return are more common in the liveborn (50%), whereas congenital infections are more common in the stillborn with NIHF.

Autopsy↗
PubMed2005

Effect of respiratory syncytial virus on apnea in weanling rats.

Apnea is a common complication of respiratory syncytial virus (RSV) infection in young infants. The purpose of this study was to determine whether this infection affects apnea triggered by sensorineural stimulation in weanling rats. We also studied which neurotransmitters are involved in this response and whether passive prophylaxis with a specific neutralizing antibody (palivizumab) confers protection against it. Weanling rats were inoculated intranasally with RSV, adenovirus, or virus-free medium. Changes in respiratory rate and apnea in response to nerve stimulation with increasing doses of capsaicin were measured by plethysmography. Capsaicin-induced apnea was significantly longer in RSV-infected rats at postinoculation days 2 (upper airways infection) and 5 (lower airways infection), and apnea-related mortality occurred only in the RSV-infected group. Reduction in the duration of apnea was observed after selective inhibition of central gamma-aminobutyric acid (GABA) type A receptors and neurokinin type 1 receptors for substance P. Prophylactic palivizumab protected against apnea and apnea-related mortality. These results suggest that sensorineural stimulation during RSV infection is associated with the development of apnea and apnea-related death in early life, whose mechanism involves the release of GABA acting on central GABA type A receptors and substance P acting on neurokinin type 1 receptors.

Animals↗
PubMed2005

Management of infants with bronchopulmonary dysplasia in North America.

The in-hospital management of infants with BPD includes minimizing the duration of mechanical ventilation and avoiding the use of high inspired oxygen concentrations while maintaining adequate oxygenation. Fluid restriction, bronchodilators, and diuretic therapy can improve lung function and reduce the need for supplemental oxygen and high ventilator settings, but do not change the ultimate course of these infants. Corticosteroids also improve lung function and accelerate weaning from oxygen and mechanical ventilation, but their use during the first weeks of life is associated with worse neurological outcome. Adequate nutrition plays an important role in lung injury protection and recovery. Infants with severe BPD frequently develop pulmonary hypertension and may benefit from the use of pulmonary vasodilators. Outpatient management must be carefully planned and carried out by experienced multidisciplinary teams. Social and financial issues must be addressed with the family and caregivers. Home oxygen and mechanical ventilation therapy are used frequently after discharge and require specialized staff and equipment. Maintenance of oxygenation and proper nutritional support are critical aspects in the post-discharge management of these infants. Immunizations and RSV prevention are also important to prevent infections in these vulnerable immunocompromised patients.

Adrenal Cortex Hormones↗
PubMed2005

The association between early tracheal colonization and bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the relationship between early tracheal colonization and bronchopulmonary dysplasia (BPD). STUDY DESIGN: This is a retrospective cohort study which included 308 inborn neonates admitted to the newborn intensive care unit at the University of Miami Jackson Memorial Medical Center between January 1997 and December 2000 with birthweight 500 to 1000 g, who required mechanical ventilation on the first day of life. Chorioamnionitis was diagnosed by maternal symptoms and histopathopathology. Tracheal cultures were obtained immediately after tracheal intubation. BPD was diagnosed in neonates who had supplemental oxygen requirement for more than 28 days. Pearson's chi(2) and Logistic Regression Analysis were used to evaluate the relationship between chorioamnionitis, positive initial tracheal cultures and BPD, after adjusting for confounding variables. RESULTS: In patients with chorioamnionitis, the incidence of early positive tracheal cultures was 41% compared to 16% in those without chorioamnionitis, (p < 0.00001). In patients with birthweight 700 to 1000 g, a positive early tracheal culture increased the risk of BPD (OR = 2.42, CI 1.05 to 5.62, p < 0.05). CONCLUSION: Preterm infants exposed to chorioamnionitis have an increased incidence of early tracheal colonization. This early tracheal colonization may predispose them to develop BPD.

Bronchopulmonary Dysplasia↗
PubMed2005

Effects of pressure support during an acute reduction of synchronized intermittent mandatory ventilation in preterm infants.

BACKGROUND: During weaning of synchronized intermittent mandatory rate in preterm infants, the spontaneous breaths must overcome the resistance of the endotracheal tube and the disease-induced respiratory loads. Pressure Support (PS) can be used as an adjunct to synchronized intermittent mandatory ventilation (SIMV) to partially unload the spontaneous breaths. OBJECTIVE: To evaluate the effects of two levels of PS as an adjunct to SIMV on gas exchange and breathing effort during an acute reduction in SIMV rate in preterm infants. METHODS: In all, 15 infants (birth weight 793 +/- 217 g, gestational age 26.4 +/- 1.5 weeks, postnatal age 15 +/- 16 days). Ventilatory support consisted of SIMV with peak inspiratory pressure (PTP) 16.3 +/- 1.3 cmH(2)O, positive end-expiratory pressure (PEEP) 4.3 +/- 0.6 cmH(2)O, and fraction of inspired oxygen (FiO(2)) 0.26 +/- 0.06. Infants were studied during four 30-minute periods: Two baseline SIMV periods and two periods of SIMV plus PS, in random order. During SIMV + PS, SIMV rate was lowered by 10 breaths per minute (b/minute) and PS was set at 3 and 6 cmH(2)O (SIMV+PS3 and SIMV + PS6, respectively). RESULTS: SIMV rate was reduced during SIMV + PS from 21.4 +/- 6.6 to 11.4 +/- 6.6 b/minute. Arterial oxygen saturation, transcutaneous carbon dioxide tension and FiO(2) remained unchanged. Minute ventilation, total respiratory rate and mean airway pressure were higher during SIMV + PS. Per-breath inspiratory effort was lower during SIMV + PS and this was more striking during SIMV + PS6. Spontaneous inspiratory effort per minute increased during SIMV + PS3, but this increase was averted during SIMV + PS6. CONCLUSION: Assistance of the spontaneous breaths with pressure support maintained gas exchange. PS of 6 cm H(2)O prevented an increase in breathing effort during an acute 50% reduction in SIMV rate.

Humans↗
PubMed2005

Patent ductus arteriosus and respiratory outcome in premature infants.

A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.

Bronchopulmonary Dysplasia↗
PubMed2005

A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants.

BACKGROUND AND OBJECTIVE: Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death. METHODS: We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (n = 509), lucinactant (n = 527), or beractant (n = 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board. RESULTS: Lucinactant reduced significantly the incidence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.52-0.89). There was no significant difference in comparison with beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less common with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). CONCLUSIONS: Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2004

Effects of a nebulized NONOate, DPTA/NO, on group B streptococcus-induced pulmonary hypertension in newborn piglets.

NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4-10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 x 10(8) CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p <0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p <0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.

Adult↗
PubMed2004

Protective effect of pentoxifylline on volume-induced lung injury in newborn piglets.

To evaluate the efficacy of pentoxifylline (PTXF) in the attenuation of lung inflammation during volume-induced lung injury (VILI) in newborn piglets, 17 newborn piglets were mechanically ventilated with a large tidal volume (50 ml/kg) for a period of 8 h. They were randomly assigned to a placebo (PL, n = 9) or a treatment group (PTXF, n = 8) that received PTXF (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h). Hemodynamics, lung mechanics and arterial blood gases were measured during the 8 h of study. Serum and tracheoalveolar fluid (TAF) platelet-activating factor (PAF) and thromboxane (TXB(2)) levels were obtained at baseline and at 8 h, while lung tissue myeloperoxidase (MPO) and wet to dry weight were assessed after the completion of the study. In the PL group, a marked increase in TAF PAF and TXB(2) levels was observed only in TAF, suggesting that the inflammatory process was localized within the lungs. A significant decrease in lung tissue MPO activity (p < 0.005) and lung wet to dry weight ratio (p < 0.04) was observed in the PTXF group. There were no differences in hemodynamics, arterial blood gases or lung mechanics measurements between groups. A significant reduction in pulmonary inflammatory response was observed during VILI in the PTXF pretreated animals. These results suggest that PTXF may be effective in modulating lung inflammation associated with mechanical ventilation in neonates.

Animals↗