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ABSTRACT: BACKGROUND AIMS: Human amnion epithelial cells (hAECs) prevent pulmonary inflammation and injury in fetal sheep exposed to intrauterine lipopolysaccharide. We hypothesized that hAECs would similarly mitigate hyperoxia-induced neonatal lung injury. METHODS: Newborn mouse pups were randomized to either normoxia (inspired O2 content (FiO2) = 0.21, n = 60) or hyperoxia (FiO2 = 0.85, n = 57). On postnatal days (PND) 5, 6 and 7, hAECs or sterile saline (control) was administered intraperitoneally. All animals were assessed at PND 14. RESULTS: Hyperoxia was associated with lung inflammation, alveolar simplification and reduced postnatal growth. Administration of hAECs to hyperoxia-exposed mice normalized body weight and significantly attenuated some aspects of hyperoxia-induced lung injury (mean linear intercept and septal crest density) and inflammation (interleukin-1α, interleukin-6, transforming growth factor-β and platelet-derived growth factor-β). However, hAECs did not significantly alter changes to alveolar airspace volume, septal tissue volume, tissue-to-airspace ratio, collagen content or leukocyte infiltration induced by hyperoxia. CONCLUSIONS: Intraperitoneal administration of hAECs to neonatal mice partially reduced hyperoxia-induced lung inflammation and structural lung damage. These observations suggest that hAECs may be a potential therapy for neonatal lung disease.
Cytotherapy 04/2013; · 3.63 Impact Factor
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ABSTRACT: Background:Intrauterine inflammation adversely affects cardiopulmonary, systemic and cerebral hemodynamics in preterm neonates but the impact on responses to endotracheal tube(ETT) suction, known to affect hemodynamics, is unknown. We hypothesized that intrauterine inflammation would alter the cardiopulmonary and cerebral hemodynamic response to open ETT suction in preterm lambs.Methods:Chronically instrumented fetuses received intra-amniotic lipopolysaccharide (LPS; to induce intrauterine inflammation) or saline at 118d gestation (term ~147d). At 125d lambs were delivered and mechanically ventilated. Open ETT suction was performed 30 minutes after delivery. Pulmonary and cerebral arterial pressures and flows were recorded continuously.Results:Intrauterine inflammation reduced pulmonary blood flow and increased pulmonary vascular resistance after preterm birth.Pulmonary blood flow and left ventricular output increasedduring and immediately after ETT suction in both groups, but values were higher in LPS-exposed lambs.Pre-ductal oxygenation significantly decreased during ETT suction, but to a greater extent in LPS-exposed lambs. Cerebral blood flow and systemic arterial pressure were increased by open ETT suction similarly in both groups.Conclusion:Intrauterine inflammationexacerbatesthe neonatal hemodynamic responseto open ETT suction.Pediatric Research (2013); doi:10.1038/pr.2013.70.
Pediatric Research 04/2013; · 2.70 Impact Factor
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ABSTRACT: Intrauterine infection, such as occurs in chorioamnionitis, is a principal cause of preterm birth and is a strong risk factor for neurological morbidity and cerebral palsy. This study aims to examine whether human amnion epithelial cells (hAECs) can be used as a potential therapeutic agent to reduce brain injury induced by intra-amniotic administration of lipopolysaccharide (LPS) in preterm fetal sheep. Pregnant ewes underwent surgery at approximately 110 days of gestation (term is approx. 147 days) for implantation of catheters into the amniotic cavity, fetal trachea, carotid artery and jugular vein. LPS was administered at 117 days; hAECs were labeled with carboxyfluorescein succinimidyl ester and administered at 0, 6 and 12 h, relative to LPS administration, into the fetal jugular vein, trachea or both. Control fetuses received an equivalent volume of saline. Brains were collected 7 days later for histological assessment of brain injury. Microglia (Iba-1-positive cells) were present in the brain of all fetuses and were significantly increased in the cortex, subcortical and periventricular white matter in fetuses that received LPS, indicative of inflammation. Inflammation was reduced in fetuses that received hAECs. In LPS fetuses, the number of TUNEL-positive cells was significantly elevated in the cortex, periventricular white matter, subcortical white matter and hippocampus compared with controls, and reduced in fetuses that received hAECs in the cortex and periventricular white matter. Within the fetal brains studied there was a significant positive correlation between the number of Iba-1-immunoreactive cells and the number of TUNEL-positive cells (R(2) = 0.19, p < 0.001). The administration of hAECs protects the developing brain when administered concurrently with the initiation of intrauterine inflammation.
Developmental Neuroscience 04/2013; · 3.63 Impact Factor
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ABSTRACT: Abstract Background: Intrauterine inflammation is associated with preterm birth and poor long-term cardiopulmonary outcomes. We aimed to determine the effect of intrauterine inflammation on the cardiopulmonary and cerebral haemodynamic transition at birth, and the response to subsequent haemodynamic challenge. Methods: Fetal instrumentation was performed at ~112 days of gestation (d: term is 147 d) for measurement of cardiopulmonary and cerebral haemodynamics. At 118 d inflammation was induced by intra-amniotic administration of lipopolysaccharide (LPS; n=7); controls (n=5) received intra-amniotic saline. At 125 d lambs were delivered and mechanically ventilated. Arterial blood gases, pulmonary and systemic arterial blood pressures and flows were measured during the perinatal period. At 10 minutes a haemodynamic challenge was administered by increasing positive end-expiratory pressure. Results. During the first 10 minutes after birth, LPS-exposed lambs had higher pulmonary vascular resistance, and lower pulmonary blood flow and left ventricular output than controls. Carotid arterial blood flow was higher in LPS-exposed lambs than controls between 3 and 7 minutes after delivery, and cerebral oxygen delivery was higher at 5 minutes. During the haemodynamic challenge, pulmonary blood flow and left ventricular output were reduced in controls but not in LPS-exposed lambs; a transient reduction in brachiocephalic arterial pressure occurred in LPS-exposed lambs but not in controls. Conclusion: Intrauterine inflammation altered the cardiopulmonary and cerebral haemodynamic transition at birth and reduced the cardiopulmonary response to a haemodynamic challenge after birth. The transient reduction in brachiocephalic arterial pressure suggests intrauterine inflammation may alter cerebrovascular control following an increase in positive end-expiratory pressure.
The Journal of Physiology 02/2013; · 4.72 Impact Factor
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ABSTRACT: Preterm birth is a major cause of perinatal mortality and long-term morbidity. Chorioamnionitis is a common cause of preterm birth. Clinical chorioamnionitis, characterised by maternal fever, leukocytosis, tachycardia, uterine tenderness, and preterm rupture of membranes, is less common than subclinical/histologic chorioamnionitis, which is asymptomatic and defined by inflammation of the chorion, amnion, and placenta. Chorioamnionitis is often associated with a fetal inflammatory response. The fetal inflammatory response syndrome (FIRS) is defined by increased systemic inflammatory cytokine concentrations, funisitis, and fetal vasculitis. Clinical and epidemiological studies have demonstrated that FIRS leads to poor cardiorespiratory, neurological, and renal outcomes. These observations are further supported by experimental studies that have improved our understanding of the mechanisms responsible for these outcomes. This paper outlines clinical and experimental studies that have improved our current understanding of the mechanisms responsible for chorioamnionitis-induced preterm birth and explores the cellular and physiological mechanisms underlying poor cardiorespiratory, neural, retinal, and renal outcomes observed in preterm infants exposed to chorioamnionitis.
Journal of pregnancy 01/2013; 2013:412831.
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Reproduction Fertility and Development 10/2012; · 2.11 Impact Factor
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ABSTRACT: Bronchopulmonary dysplasia (BPD) is a major cause of substantial lifelong morbidity in preterm infants. Despite a better understanding of the pathophysiology of BPD and significant research effort into its management, there remains today no effective treatment. Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD. Recent research supports a therapeutic role for cell transplantation in the management of a variety of acute and chronic adult and childhood lung diseases, with potential of such therapy to reduce inflammation and prevent acute lung injury. However, considerable uncertainties remain regarding cell therapies before they can be established as safe and effective clinical treatments for BPD. This review summarizes the current literature investigating cell therapies in lung disease, with particular focus on the various types of cells available and their specific properties in the context of a future therapy for BPD.
PEDIATRICS 09/2012; 130(4):727-37. · 4.47 Impact Factor
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ABSTRACT: 1. Intrauterine infection or inflammation is common in cases of preterm birth. Preterm infants are at risk of acute respiratory distress as a result of lung immaturity; evidence of exposure to infection and/or inflammation before birth is associated with a reduced risk of neonatal respiratory distress syndrome (RDS). Experimentally induced intrauterine inflammation or infection in sheep causes a precocious increase in pulmonary surfactant in the preterm lungs that improves preterm lung function, consistent with the reduced risk of RDS in human infants exposed to infection and/or inflammation before birth. 2. The effects of intrauterine inflammation on fetal lung development appear to result from direct action of proinflammatory stimuli within the lungs rather than by systemic signals, such as the classical glucocorticoid-mediated lung maturation pathway. However, paracrine and/or autocrine production and/or metabolism of glucocorticoids in fetal lung tissue may occur as a result of inflammation-induced changes in the expression of 11β-hydroxysteroid dehydrogenase (types 1 and 2). 3. Likely candidates that mediate inflammation-induced surfactant production by the preterm lung include prostaglandin E(2) and/or other arachidonic acid metabolites. Intrauterine inflammation induces the expression of enzymes responsible for prostaglandin production in fetal lung tissue. Inhibition of prostaglandin production prevents, at least in part, the effects of inflammation on fetal lungs. 4. Our experiments are identifying mechanisms of surfactant production by the preterm lungs that may be exploited as novel therapies for preventing respiratory distress in preterm infants. Elucidation of the effects of inflammation on the fetal lungs and other organs will allow more refined approaches to the care of preterm infants exposed to inflammation in utero.
Clinical and Experimental Pharmacology and Physiology 07/2012; 39(9):824-30. · 1.85 Impact Factor
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ABSTRACT: OBJECTIVE: The 2010 ILCOR neonatal resuscitation guidelines do not specify appropriate inflation times for the initial lung inflations in apnoeic newborn infants. The authors compared three ventilation strategies immediately after delivery in asphyxiated newborn lambs. DESIGN: Experimental animal study. SETTING: Facility for animal research. SUBJECTS: Eighteen near-term lambs (weight 3.5-3.9 kg) delivered by caesarean section. INTERVENTIONS: Asphyxia was induced by occluding the umbilical cord and delaying ventilation onset (10-11 min) until mean carotid blood pressure (CBP) was ≤22 mm Hg. Animals were divided into three groups (n=6) and ventilation started with: (1) inflation times of 0.5 s at a ventilation rate 60/min, (2) five 3 s inflations or (3) a single 30 s inflation. Subsequent ventilation used inflations at 0.5 s at 60/min for all groups. MAIN OUTCOME MEASURES: Times to reach a heart rate (HR) of 120 bpm and a mean CBP of 40 mm Hg. Secondary outcome was change in lung compliance. RESULTS: Median time to reach HR 120 bpm and mean CBP 40 mm Hg was significantly shorter in the single 30 s inflation group (8 s and 74 s) versus the 5×3 s inflation group (38 s and 466 s) and the conventional ventilation group (64 s and 264 s). Lung compliance was significantly better in the single 30 s inflation group. CONCLUSION: A single sustained inflation of 30 s immediately after birth improved speed of circulatory recovery and lung compliance in near-term asphyxiated lambs. This approach for neonatal resuscitation merits further investigation.
Archives of Disease in Childhood - Fetal and Neonatal Edition 07/2012; · 3.05 Impact Factor
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ABSTRACT: PurposeThe relative contributions of factors influencing lung injury immediately after birth are poorly understood. We hypothesized
that oxygen content and humidity of inspired air would influence markers of pulmonary inflammation in ventilated lambs.
MethodsLambs delivered at 140days gestation (term=150days) were assigned to one of five groups (n=5–6/group): unventilated controls, or ventilation with 21 or 100% O2 that was either heated and humidified or cold and dry. Lambs were ventilated gently for 3h: blood gases were recorded regularly.
Bronchoalveolar lavage and samples of tracheal mucosa and lung were collected post mortem.
ResultsArterial pH was lower [mean difference (95% CI): −0.07 (−0.13, −0.03)], while there was an increase in PaCO2 [mean difference (95% CI): 10.2 (2.4, 17.9)] and fold change in lung pro-inflammatory IL-1β cytokine mRNA [mean difference
(95% CI): 28.3 (0.3, 56.2)] or IL-8 [mean difference (95% CI): 27.8 (7.9, 47.7)] cytokine mRNA expression with 100% O2 relative to 21% O2. Cold dry inspired gas did not influence gas exchange or dynamic mechanics at 3h compared to heated humidified gas. Compared
to 100% inspired O2, cold dry inspired gas had less marked effect on fold change in lung pro-inflammatory IL-1β cytokine mRNA [mean difference
(95% CI): 27.2 (−0/8, 55.1)] or IL-8 [mean difference (95% CI): 14.5 (5.5, 34.4)] cytokine mRNA expression, although cilial
dysfunction/damage was evident on electron microscopy, especially when exposure to cold dry gas was combined with hyperoxia.
ConclusionsIn near-term neonatal lambs ventilated for 3h, hyperoxia was associated a more powerful stimulus for pulmonary dysfunction
and upregulation of inflammatory cytokines than cold dry gas.
Intensive Care Medicine 04/2012; 35(12):2157-2163. · 5.40 Impact Factor
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ABSTRACT: Introduction:Caffeine administration is associated with a reduction in bronchopulmonary dysplasia, assisted ventilation, patent ductus arteriosus (DA) and cerebral palsy in preterm infants, but the mechanisms are unknown. Our aim was to determine the effects of acute caffeine administration on renal and pulmonary function in preterm lambs.Methods:Lambs were delivered by caesarean section at ~126 days of gestation and ventilated with a tidal volume of 5 ml/kg, 60 breaths/min and 5 cmH(2)O positive end-expiratory pressure. After 30 minutes, lambs received 40 mg/kg caffeine i.v (n=7) or saline (controls; n=6) over 30 minutes and were ventilated for 2 hours.Results:Arterial caffeine concentrations reached 35.9 ± 7.8 mg/l. Urine output was significantly higher after caffeine treatment than in controls (5.86 ± 1.95 vs 0.76 ± 0.94 ml/kg, area under curve p=0.041). Mean heart rate was significantly higher after caffeine treatment than in controls (211 ± 8 vs 169 ± 15 beats per minute, p<0.05) and remained higher for the experimental period.Discussion:Caffeine did not affect pulmonary artery or DA blood flows or other renal, respiratory or cardiovascular parameters examined. Neonatal caffeine administration increased heart rate and urine output but had little effect on pulmonary function in ventilated preterm lambs.
Pediatric Research 04/2012; · 2.70 Impact Factor
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ABSTRACT: Intrauterine inflammation is a common antecedent of preterm birth and can alter the development of the fetal thymus, the site of development, and maturation of T lymphocytes. The effects of intrauterine inflammation on specific thymic T lymphocyte populations are largely unknown. We hypothesized that intrauterine inflammation would alter fetal thymic T cell populations. Immunohistochemistry was used to quantitate the relative proportions of thymic cortical and medullary cell populations in fetal sheep 7 days after intra-amniotic lipopolysaccharide (LPS) injection. The proportions of CD8(+)and MHC II(+) cells in the fetal thymus were reduced in response to LPS. The ratio of CD4:CD8 cells was increased by LPS exposure. No changes were observed in the percentage of CD4(+), γδ(WC1)(+), CD45R(+)B cells, or CD44(+) cells. These studies indicate that intrauterine inflammation impacts thymic composition of CD8 T cells and the development and/or activation of CD4 T cells in the fetal thymus.
Reproductive sciences (Thousand Oaks, Calif.) 03/2012; 19(7):740-7. · 2.31 Impact Factor
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ABSTRACT: Males born preterm are at greater risk of illness and death than females, principally due to respiratory disease. Much of the excess morbidity occurs within the first few hours of life. Therefore, the aim of the present study was to investigate whether or not differences in the cardiopulmonary transition soon after birth underlie the increased morbidity in males after preterm birth. Nine female and thirteen male lambs (128±2 days gestation) underwent surgery immediately before delivery for implantation of a pulmonary arterial flow-probe and catheters into the main pulmonary artery and a carotid artery. After birth lambs were ventilated for 30 min (tidal volume 7 mL kg(-1)) while anaesthetised. Arterial pressures and flows were recorded in real time and left-ventricular output measured using Doppler echocardiography. Before birth, fetal cardiopulmonary haemodynamics, arterial blood gases, pH, glucose and lactate did not differ between sexes. Similarly, in the neonatal period there were no significant differences in arterial blood gas status, ventilation parameters, respiratory indices or cardiopulmonary haemodynamics between the sexes. Our data show that the cardiopulmonary transition at birth in ventilated, anaesthetised preterm lambs is not influenced by sex. Thus, the neonatal 'male disadvantage' is not explained by an impaired cardiovascular transition at birth.
Reproduction Fertility and Development 03/2012; 24(3):510-6. · 2.11 Impact Factor
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ABSTRACT: Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators, and PGE(2) has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE(2) concentrations in response to IA LPS and pulmonary gene expression for PG synthetic [prostaglandin H synthase-2 (PGHS-2) and PGE synthase (PGES)] and PG-metabolizing [prostaglandin dehydrogenase (PGDH)] enzymes and PGE(2) receptors. Our second study aimed to block LPS-induced increases in PGE(2) with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and surfactant protein mRNA expression. Pregnant ewes received an IA saline or LPS injection at 118 days of gestation. In study 1, fetal plasma and amniotic fluid were sampled before and at 2, 4, 6, 12, and 24 h after injection and then daily, and fetuses were delivered 2 or 7 days later. Amniotic fluid PGE(2) concentrations increased (P < 0.05) 12 h and 3-6 days after LPS. Fetal lung PGHS-2 mRNA and PGES mRNA increased 2 (P = 0.0084) and 7 (P = 0.014) days after LPS, respectively. In study 2, maternal intravenous nimesulide or vehicle infusion began immediately before LPS or saline injection and continued until delivery 2 days later. Nimesulide inhibited LPS-induced increases in PGE(2) and decreased fetal lung IL-1β and IL-8 mRNA (P ≤ 0.002) without altering lung inflammatory cell infiltration. Nimesulide decreased surfactant protein (SP)-A (P = 0.05), -B (P = 0.05), and -D (P = 0.0015) but increased SP-C mRNA (P = 0.023). Thus PGHS-2 mediates, at least in part, fetal pulmonary responses to inflammation.
AJP Lung Cellular and Molecular Physiology 01/2012; 302(7):L664-78. · 3.66 Impact Factor
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Graeme R Polglase,
Suzanne L Miller,
Samantha K Barton,
Ana A Baburamani,
Flora Y Wong,
James D S Aridas,
Andrew W Gill, Timothy J M Moss,
Mary Tolcos,
Martin Kluckow,
Stuart B Hooper
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ABSTRACT: Preterm infants can be inadvertently exposed to high tidal volumes (V(T)) in the delivery room, causing lung inflammation and injury, but little is known about their effects on the brain. The aim of this study was to compare an initial 15 min of high V(T) resuscitation strategy to a less injurious resuscitation strategy on cerebral haemodynamics, inflammation and injury.
Preterm lambs at 126 d gestation were surgically instrumented prior to receiving resuscitation with either: 1) High V(T) targeting 10-12 mL/kg for the first 15 min (n = 6) or 2) a protective resuscitation strategy (Prot V(T)), consisting of prophylactic surfactant, a 20 s sustained inflation and a lower initial V(T) (7 mL/kg; n = 6). Both groups were subsequently ventilated with a V(T) 7 mL/kg. Blood gases, arterial pressures and carotid blood flows were recorded. Cerebral blood volume and oxygenation were assessed using near infrared spectroscopy. The brain was collected for biochemical and histologic assessment of inflammation, injury, vascular extravasation, hemorrhage and oxidative injury. Unventilated controls (UVC; n = 6) were used for comparison.
High V(T) lambs had worse oxygenation and required greater ventilatory support than Prot V(T) lambs. High V(T) resulted in cerebral haemodynamic instability during the initial 15 min, adverse cerebral tissue oxygenation index and cerebral vasoparalysis. While both resuscitation strategies increased lung and brain inflammation and oxidative stress, High V(T) resuscitation significantly amplified the effect (p = 0.014 and p<0.001). Vascular extravasation was evident in the brains of 60% of High V(T) lambs, but not in UVC or Prot V(T) lambs.
High V(T) resulted in greater cerebral haemodynamic instability, increased brain inflammation, oxidative stress and vascular extravasation than a Prot V(T) strategy. The initiation of resuscitation targeting Prot V(T) may reduce the severity of brain injury in preterm neonates.
PLoS ONE 01/2012; 7(6):e39535. · 4.09 Impact Factor
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American journal of obstetrics and gynecology 12/2011; · 3.28 Impact Factor
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ABSTRACT: We determined the effects of prenatal dexamethasone administration in early gestation on development of the hypothalamic-pituitary-adrenal (HPA) axis up to 7 months of postnatal age with measurements of hormone levels and gene expression. Plasma adrenocorticotropic hormone and cortisol levels after corticotropin-releasing hormone (CRH)/arginine vasopressin challenge were lower in treatment females than in control females and treatment males. Calculation of cortisol to adrenocorticotropic hormone ratios indicated however that the adrenals of treatment females were more responsive to adrenocorticotropic hormone than control females or treatment males. Effects of treatment and sex dependence at 7 months of age were observed in levels of hypothalamic CRH messenger RNA (mRNA), hypothalamic arginine vasopressin mRNA, pituitary proopiomelanocortin mRNA, pituitary prohormone convertase 1 and prohormone convertase 2, glucocorticoid receptor and mineralocorticoid receptor in the hypothalamus and hippocampus, adrenal adrenocorticotropic hormone receptor, steroidogenic acute regulatory, 3β hydroxysteroid dehydrogenase, and 11β hydroxysteroid dehydrogenase type 2 mRNA. The results indicate that exposure to glucocorticoids in early pregnancy produces persisting and sex-dependent effects on the hypothalamic-pituitary-adrenal axis at 7 months of age.
Reproductive sciences (Thousand Oaks, Calif.) 11/2011; 19(3):260-70. · 2.31 Impact Factor
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Graeme R Polglase,
Ilias Nitsos,
Ana A Baburamani,
Kelly J Crossley,
Melanie K Slater,
Andrew W Gill,
Beth J Allison, Timothy J M Moss,
J Jane Pillow,
Stuart B Hooper,
Martin Kluckow
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ABSTRACT: Cerebral blood flow disturbance is a major contributor to brain injury in the preterm infant. The initiation of ventilation may be a critical time for cerebral hemodynamic disturbance leading to brain injury in preterm infants, particularly if they are exposed to inflammation in utero. We aimed to determine whether exposure to inflammation in utero alters cardiopulmonary hemodynamics, resulting in cerebral hemodynamic disturbance and related brain injury during the initiation of ventilation. Furthermore, we aimed to determine whether inflammation in utero alters the cerebral hemodynamic response to challenge induced by high mean airway pressures. Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) or saline either 2 or 4-days before preterm delivery (at 128 ± 1 days of gestation). Lambs were surgically instrumented for assessment of pulmonary and cerebral hemodynamics before delivery and positive pressure ventilation. After 30 min, lambs were challenged hemodynamically by incrementing and decrementing positive end-expiratory pressure. Blood gases, arterial pressures, and blood flows were recorded. The brain was collected for biochemical and histological assessment of inflammation, brain damage, vascular extravasation, hemorrhage, and oxidative injury. Carotid arterial pressure was higher and carotid blood flow was more variable in 2-day LPS lambs than in controls during the initial 15 min of ventilation. All lambs responded similarly to the hemodynamic challenge. Both 2- and 4-day LPS lambs had increased brain interleukin (IL)-1β, IL-6, and IL-8 mRNA expression; increased number of inflammatory cells in the white matter; increased incidence and severity of brain damage; and vascular extravasation relative to controls. Microvascular hemorrhage was increased in 2-day LPS lambs compared with controls. Cerebral oxidative injury was not different between groups. Antenatal inflammation causes adverse cerebral hemodynamics and increases the incidence and severity of brain injury in ventilated preterm lambs.
Journal of Applied Physiology 11/2011; 112(3):481-9. · 3.75 Impact Factor
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ABSTRACT: A sustained inflation (SI) facilitates lung aeration after birth but may impair the neonatal cardiovascular transition. We aimed to determine the effect of an initial SI on pulmonary arterial and carotid blood flow (PBF and CBF) after preterm birth. Fetal sheep were instrumented at ∼ 122 d of gestation (d). Lambs were delivered at ∼ 127 d and received either an initial SI (40 cm H2O for 1 min or until a volume of 20 mL/kg was administered) followed by ventilation for 30 min (SI; n = 7) or ventilation for 30 min (non-SI; n = 6). At 10 min after ventilation onset, inspired O2 content increased from 21 to 100% for 10 min. PBF, CBF, pulmonary arterial and carotid pressures, tidal volume, and inspiratory pressures were recorded. PBF was greater during the SI (p < 0.05) but thereafter was similar between groups. Non-SI lambs were hypoxemic and had higher CBF than SI lambs (p < 0.05). Cerebral oxygen delivery was constant in SI lambs but increased ∼ 4-fold in non-SI lambs during ventilation with 100% O2 (p < 0.05). Lung compliance and respiratory status were better in SI than non-SI lambs (p < 0.05). A SI improved lung function without adverse circulatory effects, seemed to stabilize neonatal cerebral O2 delivery, and may protect against cerebral hyperoxia.
Pediatric Research 07/2011; 70(1):56-60. · 2.70 Impact Factor
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ABSTRACT: The purpose of this study was to determine whether human amnion epithelial cells (hAECs) can modulate the pulmonary developmental consequences of intrauterine inflammation in fetal sheep that are exposed to intraamniotic lipopolysaccharide (LPS) injection.
At 117 days' gestation, fetal sheep (n=16) received intraamniotic LPS (20 mg). hAECs were delivered at 0, 6, and 12 hours into the fetal jugular vein (n=4), trachea (n=4), or both (n=4). Controls (n=6) received equivalent administration of saline solution. Lungs were collected at 124 days.
Intraamniotic LPS caused pulmonary inflammation and altered lung structure and function. hAECs attenuated changes in lung function and structure that had been induced by LPS: lung volume, 40 cm H2O (P<.05, intravenous+intratracheal hAECs vs LPS), tissue-to-airspace ratio (P<.05, intravenous+intratracheal hAECs vs LPS), and septal crest density (P<.001, all hAEC groups vs LPS). Leukocyte infiltration of the lungs was not reduced by hAECs; however, inflammatory cytokines were reduced (tumor necrosis factor-α, P<.01, vs LPS; interleukin-1b, P<.01, vs LPS; interleukin-6, P<.01 vs LPS). Surfactant protein A and C messenger RNA was increased by LPS, although this was not statistically significant (P>.05 vs control); there were significant increases in all hAEC-treated animals (surfactant protein-A, P<.05 vs LPS; surfactant protein-C, P<.01 vs LPS).
Human amnion epithelial cells attenuate the fetal pulmonary inflammatory response to experimental intrauterine inflammation and reduce, but (as administered in our study) do not prevent, consequent alterations in lung development.
American journal of obstetrics and gynecology 04/2011; 205(2):156.e26-33. · 3.28 Impact Factor
