Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets.

BACKGROUND: High-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model. METHODS: Twelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device ("machine") or the two-thumb encircling technique ("human"). CC was superimposed with sustained inflations. RESULTS: Twelve newborn piglets (age 0-3 days, weight 2.12 ± 0.17 kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax) compared to human-delivered CC. CONCLUSIONS: During machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia. IMPACT: Machine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.

Chest compressions superimposed with sustained inflations during cardiopulmonary resuscitation in asphyxiated pediatric piglets.

BACKGROUND: Pediatric resuscitation guidelines recommend continuous chest compression with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation. We recently described that providing a constant high distending pressure, or sustained inflation (SI) while performing continuous chest compressions (CC = CC + SI) reduces time to return of spontaneous circulation (ROSC) in neonatal and pediatric piglets with asphyxia-induced cardiac arrest. METHODS: To determine if CC + SI compared to CCaV will improve frequency of achieving ROSC and reduce time to ROSC in asphyxiated pediatric piglets. Twenty-eight pediatric piglets (21-24 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 14/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The mean(SD) duration of resuscitation was significantly reduced with CC + SI compared to CCaV with 208(190) vs. 388(258)s, p = 0.045, respectively. The number of piglets achieving ROSC with CC + SI and CCaV were 12/14 vs. 6/14, p = 0.046. Minute ventilation, end-tidal carbon dioxide, ventilation rate, and positive end expiratory pressures were also significantly improved with CC + SI. CONCLUSIONS: CC + SI improves duration of resuscitation and increases number of piglets achieving ROSC secondary to improved minute ventilation. IMPACT: Chest compressions superimposed with sustained inflation resulted in shorter duration of resuscitation Chest compressions superimposed with sustained inflation resulted in higher number of piglets achieving return of spontaneous circulation Further animal studies are needed to examine chest compressions superimposed with sustained inflation.

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets.

BACKGROUND: Current neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets. DESIGN/METHODS: Newborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured. RESULTS: Median (IQR) time to ROSC was 172(103-418)s, 157(100-413)s, 122(93-289)s, and 276(117-480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61). CONCLUSION: Time to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation. IMPACT: Time to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine. Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets. Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups. Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon.

Pulmonary and Neurologic Effects of Mesenchymal Stromal Cell Extracellular Vesicles in a Multifactorial Lung Injury Model.

Rationale: Bronchopulmonary dysplasia, a chronic respiratory condition originating from preterm birth, is associated with abnormal neurodevelopment. Currently, there is an absence of effective therapies for bronchopulmonary dysplasia and its associated brain injury. In preclinical trials, mesenchymal stromal cell therapies demonstrate promise as a therapeutic alternative for bronchopulmonary dysplasia. Objectives: To investigate whether a multifactorial neonatal mouse model of lung injury perturbs neural progenitor cell function and to assess the ability of human umbilical cord-derived mesenchymal stromal cell extracellular vesicles to mitigate pulmonary and neurologic injury. Methods: Mice at Postnatal Day 7 or 8 were injected intraperitoneally with LPS and ventilated with 40% oxygen at Postnatal Day 9 or 10 for 8 hours. Treated animals received umbilical cord-mesenchymal stromal cell-derived extracellular vesicles intratracheally preceding ventilation. Lung morphology, vascularity, and inflammation were quantified. Neural progenitor cells were isolated from the subventricular zone and hippocampus and assessed for self-renewal, in vitro differentiation ability, and transcriptional profiles. Measurements and Main Results: The multifactorial lung injury model produced alveolar and vascular rarefaction mimicking bronchopulmonary dysplasia. Neural progenitor cells from lung injury mice showed reduced neurosphere and oligodendrocyte formation, as well as inflammatory transcriptional signatures. Mice treated with mesenchymal stromal cell extracellular vesicles showed significant improvement in lung architecture, vessel formation, and inflammatory modulation. In addition, we observed significantly increased in vitro neurosphere formation and altered neural progenitor cell transcriptional signatures. Conclusions: Our multifactorial lung injury model impairs neural progenitor cell function. Observed pulmonary and neurologic alterations are mitigated by intratracheal treatment with mesenchymal stromal cell-derived extracellular vesicles.

Evidence for vasopressors during cardiopulmonary resuscitation in newborn infants.

An estimated 0.1% of term infants and up to 15% of preterm infants (2-3 million worldwide) need extensive resuscitation, defined as chest compression and 100% oxygen with or without epinephrine in the delivery room. Despite these interventions, infants receiving extensive resuscitation in the DR have a high incidence of mortality and neurologic morbidity. Successful resuscitation from neonatal cardiac arrest requires the delivery of high-quality chest compression using the most effective vasopressor with the optimal dose, timing, and route of administration during CPR. Current neonatal resuscitation guidelines recommend administration of epinephrine once CPR has started at a dose of 0.01-0.03 mg/kg preferably given intravenously, with repeated doses every 3-5 min until return of spontaneous circulation. This review examines the current evidence for epinephrine and alternative vasopressors during neonatal cardiopulmonary resuscitation.

Effects of epinephrine on hemodynamic changes during cardiopulmonary resuscitation in a neonatal piglet model.

BackgroundAsphyxia is the most common reason for newborns to fail to make a successful fetal-to-neonatal transition. There is currently a lack of data evaluating hemodynamic effects of epinephrine during neonatal cardiopulmonary resuscitation.MethodsTwenty-four newborn piglets were exposed to asphyxia. Thereafter, positive pressure ventilation was commenced for 30 s, followed by chest compressions (CC). Piglets were randomized into three experimental groups: 3:1 compression:ventilation ratio; CC during sustained inflation (SI) at a rate of 90 CC per minute, or CC during SI at a rate of 120 CC per minute. Epinephrine (0.01 mg/kg per dose) was administered to a maximum of four doses. Hemodynamic parameters were measured throughout the experiment.ResultsAnimals were divided into survivors and nonsurvivors. End-diastolic and developed pressures declined after epinephrine administration in the survivor group. dp/dt min was significantly higher in the survivor group whereas dp/dt max showed no significant differences. Epinephrine had no effect on either heart rate or cardiac output in both groups. Ejection fraction increased after epinephrine with no significant difference between groups.ConclusionEpinephrine did not affect survival rates or return of spontaneous circulation in our postnatal porcine model of neonatal asphyxia.

Review of Routes to Administer Medication During Prolonged Neonatal Resuscitation.

OBJECTIVE: During neonatal cardiopulmonary resuscitation, early establishment of vascular access is crucial. We aimed to review current evidence regarding different routes for the administration of medications during neonatal resuscitation. DATA SOURCES: We reviewed PubMed, EMBASE, and Google Scholar using MeSH terms "catheterization," "umbilical cord," "delivery room," "catecholamine," "resuscitation," "simulation," "newborn," "infant," "intraosseous," "umbilical vein catheter," "access," "intubation," and "endotracheal." STUDY SELECTION: Articles in all languages were included. Initially, we aimed to identify only neonatal studies and limited the search to randomized controlled trials. DATA EXTRACTION: Due to a lack of available studies, studies in children and adults, as well as animal studies and also nonrandomized studies were included. DATA SYNTHESIS: No randomized controlled trials comparing intraosseous access versus peripheral intravascular access versus umbilical venous catheter versus endotracheal tube versus laryngeal mask airway or any combination of these during neonatal resuscitation in the delivery room were identified. Endotracheal tube: endotracheal tube epinephrine administration should be limited to situations were no vascular access can be established. Laryngeal mask airway: animal studies suggest that a higher dose of epinephrine for endotracheal tube and laryngeal mask airway is required compared with IV administration, potentially increasing side effects. Umbilical venous catheter: European resuscitation guidelines propose the placement of a centrally positioned umbilical venous catheter during neonatal cardiopulmonary resuscitation; intraosseous access: case series reported successful and quick intraosseous access placement in newborn infants. Peripheral intravascular access: median time for peripheral intravascular access insertion was 4-5 minutes in previous studies. CONCLUSIONS: Based on animal studies, endotracheal tube administration of medications requires a higher dose than that by peripheral intravascular access or umbilical venous catheter. Epinephrine via laryngeal mask airway is feasible as a noninvasive alternative approach for drug delivery. Intraosseous access should be considered in situations with difficulty in establishing other access. Randomized controlled clinical trials in neonates are required to compare all access possibilities described above.

Does lack of glutathione peroxidase 1 gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?

Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 (GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+ and GPx1-/- C57Bl/6J mice were exposed to 21% O2 (Air) or 40% O2 (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and GPx1-4 and catalase gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of GPx1 expression and further decreased by hyperoxia. GPx1 expression was increased in GPx1+/+Hyp mice and decreased in both GPx1-/- groups. On P56d, heme oxygenase-1 was increased by hyperoxia when GPx1 was absent. There were significantly more immune cells from Hyp groups than from the GPx1+/+Air group and a greater proportion of lymphocytes in GPx1-/-Hyp mice. GPx1 expression was significantly decreased in GPx1-/- mice; GPx2-4 and catalase expression was increased in GPx1-/-Hyp mice compared with other groups. Tissue fraction was decreased in GPx1-/-Air mice; bronchiolar smooth muscle was decreased in GPx1-/- mice. GPx1 does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of GPx2-4 and catalase in GPx1-/-Hyp mice suggests gene redundancy within the model.

Cell-based therapies for neonatal lung disease.

Preterm birth occurs in approximately 11 % of all births worldwide. Advances in perinatal care have enabled the survival of preterm infants born as early as 23-24 weeks of gestation. However, many are affected by bronchopulmonary dysplasia (BPD)-a common respiratory complication of preterm birth, which has life-long consequences for lung health. Currently, there is no specific treatment for BPD. Recent advances in stem cell research have opened new therapeutic avenues for prevention/repair of lung damage. This review summarizes recent pre-clinical data and early clinical translation of cell-based therapies for BPD.

Oxygen Saturation and Heart Rate Ranges in Very Preterm Infants Requiring Respiratory Support at Birth.

OBJECTIVE: To evaluate the changes in preductal oxygen saturation (SpO2) and heart rate in preterm infants receiving continuous positive airway pressure (CPAP) and/or positive-pressure ventilation (PPV) at birth. STUDY DESIGN: A prospective observational study at birth of infants aged <32 weeks separated into 2 gestational age (GA) groups: 230/7-276/7 weeks (group 1) and 280/7-316/7 weeks (group 2). Infants received delayed cord clamping (DCC) in accordance with institutional protocol. CPAP and/or PPV was applied at the clinical team's discretion. SpO2 and heart rate were recorded every minute for 10 minutes. Preductal SpO2 was targeted according to published nomograms. For heart rate, the goal was to maintain a stable heart rate >100 bpm. RESULTS: The study cohort comprised 96 group 1 infants (mean GA, 26 ± 1 weeks; mean birth weight, 818 ± 208 g) and 173 group 2 infants (mean GA, 30 ± 1 weeks; mean birth weight, 1438 ± 374 g). In general, infants requiring respiratory support reached target values for heart rate and SpO2 more slowly than the published nomograms for spontaneously breathing preterm infants without respiratory support. Infants receiving CPAP reached SpO2 and heart rate targets faster than infants receiving PPV. In group 1, but not group 2 infants, DCC resulted in higher SpO2 and heart rate. CONCLUSION: SpO2 and heart rate do not quickly and reliably reach the values achieved by spontaneously breathing preterm infants not requiring respiratory support.

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

BACKGROUND: Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. METHODS AND RESULTS: Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. CONCLUSIONS: Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage.

Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure.

Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture.

Exhaled Carbon Dioxide and Neonatal Breathing Patterns in Preterm Infants after Birth.

OBJECTIVES: To examine the amount of exhaled carbon dioxide (ECO2) with different breathing patterns in spontaneously breathing preterm infants after birth. STUDY DESIGN: Preterm infants had a facemask attached to a combined carbon dioxide/flow sensor placed over their mouth and nose to record ECO2 and gas flow. A breath-by-breath analysis of the first 5 minutes of the recording was performed. RESULTS: Thirty spontaneously breathing preterm infants, gestational age (mean ± SD) 30 ± 2 weeks and birth weight 1635 ± 499 g were studied. ECO2 from normal breaths and slow expirations was significantly larger than with other breathing patterns (P < .001). ECO2 per breath also increased with gestational age P < .001. The expiratory hold pattern was the most prevalent breathing pattern both during the first minute of recording and overall. Breathing pattern proportions also varied by gestational age. Finally, ECO2 from the fifth minute of recording was significantly greater than that produced during the first 4 minutes of recording (P ≤ .029). CONCLUSIONS: ECO2 varies with different breathing patterns and increases with gestational age and over time. ECO2 may be an indicator of lung aeration and that postnatal ECO2 monitoring may be useful in preterm infants in the delivery room.

Spontaneously Breathing Preterm Infants Change in Tidal Volume to Improve Lung Aeration Immediately after Birth.

OBJECTIVE: To examine the temporal course of lung aeration at birth in preterm infants <33 weeks gestation. STUDY DESIGN: The research team attended deliveries of preterm infants <33 weeks gestation at the Royal Alexandra Hospital. Infants who received only continuous positive airway pressure were eligible for inclusion. A combined carbon dioxide (CO2) and flow-sensor was placed between the mask and the ventilation device. To analyze lung aeration patterns during spontaneous breathing, tidal volume (VT), and exhaled CO2 (ECO2) were recorded for the first 100 breaths. RESULTS: Thirty preterm infants were included with a total of 1512 breaths with mask leak <30%. Mean (SD) gestational age and birth weight was 30 (1) weeks and 1478 (430) g. Initial VT and ECO2 for the first 30 breaths was 5-6 mL/kg and 15-22 mm Hg, respectively. VT and ECO2 increased over the next 20 breaths to 7-8 mL/kg and 25-32 mm Hg, respectively. For the remaining observation period VT decreased to 4-6 mL/kg and ECO2 continued to increase to 35-37 mm Hg. CONCLUSIONS: Preterm infants begin taking deeper breaths approximately 30 breaths after initiating spontaneous breathing to inflate their lungs. Concurrent CO2 removal rises as alveoli are recruited. Lung aeration occurs in 2 phases: initially, large volume breaths with poor alveolar aeration followed by smaller breaths with elimination of CO2 as a consequence of adequate aeration.

Hypoxia-inducible factors promote alveolar development and regeneration.

Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.

Cardiopulmonary resuscitation with chest compressions during sustained inflations: a new technique of neonatal resuscitation that improves recovery and survival in a neonatal porcine model.

BACKGROUND: Guidelines on neonatal resuscitation recommend 90 chest compressions (CCs) and 30 manual inflations (3:1) per minute in newborns. The study aimed to determine whether CC s during sustained inflations (SIs) improves the recovery of asphyxiated newborn piglets in comparison with coordinated 3:1 resuscitation. METHODS AND RESULTS: Term newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia. Piglets were randomly assigned to receive either 3:1 resuscitation (3:1 group) or CCs during SIs (SI group) when the heart rate decreased to 25% of baseline. Piglets randomly assigned to the SI group received SIs with a pressure of 30 cm H2O for 30 s. During the SI, CCs at a rate of 120/min were provided. SI was interrupted after 30 s for 1 s before a further 30-s SI was provided. CCs were continued throughout SIs. CCs and SI were continued until the return of spontaneous circulation. Continuous respiratory parameters, cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured. Mean (standard deviation) time for return of spontaneous circulation was significantly reduced in SI group versus 3:1 group (32 [11] s versus 205 [113] s, respectively). In the SI group, administration of oxygen and epinephrine was significantly lower, whereas minute ventilation and exhaled CO2 were significantly increased. The SI group had significantly higher mean systemic and pulmonary arterial pressures during resuscitation in comparison with the 3:1 group (51 [10] versus 31 [5] mm Hg; 41[7] versus 31 [7] mm Hg, respectively; all P<0.05), with improved cardiac output and carotid blood flow. CONCLUSIONS: Combining CCs and SIs significantly improved the return of spontaneous circulation with better hemodynamic recovery in asphyxiated newborn piglets in comparison with standard coordinated 3:1 resuscitation.

Animal models of bronchopulmonary dysplasia. The term rat models.

Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model.

Tidal volumes in spontaneously breathing preterm infants supported with continuous positive airway pressure.

OBJECTIVE: To describe changes in tidal volume (VT) and their correlation to changes in oxygen saturation and heart rate in spontaneously breathing preterm infants immediately after birth. STUDY DESIGN: In this prospective observational, 2-center study, a flow sensor was attached to the facemask of spontaneously breathing infants born at <37 weeks' gestational age who received continuous positive airway pressure (CPAP) immediately after birth. Respiratory function, heart rate, and oxygen saturation were continuously recorded during spontaneous breathing. RESULTS: Fifty-five infants (mean [SD] gestational age 31 [26-36] weeks and birth weight 1647 [500] g) received mask CPAP in the delivery room. CPAP was started at a median (IQR) 90 (60-118) seconds after birth and was delivered for 720 (300-900) seconds. Median VT ranged between 4.2 and 5.8 mL/kg with the individual VT varied between 0.9 and 19.8 mL/kg. Overall, VT increased over the first few minutes after birth and decreased thereafter. The increase in saturation after birth lagged behind the published normal ranges for spontaneously breathing preterm infants without CPAP. CONCLUSIONS: The 50th percentile for spontaneous VT in preterm infants during mask CPAP ranged from 4.2 to 5.8 mL/kg, with wide individual variation observed in the first minutes after birth. Preterm infants requiring CPAP after birth may take longer to achieve so-called "normal" saturation targets.

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

BACKGROUND: Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. METHODS: Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 µg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. RESULTS AND DISCUSSION: Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

Influence of mask type and mask position on the effectiveness of bag-mask ventilation in a neonatal manikin.

UNLABELLED: Anatomical face mask with an air cushion rim might be placed accidentally in a false orientation on the newborn's face or filled with various amounts of air during neonatal resuscitation. Both false orientation as well as variable filling may reduce a tight seal and therefore hamper effective positive pressure ventilation (PPV). We aimed to measure the influence of mask type and mask position on the effectiveness of PPV. Twenty neonatal staff members delivered PPV to a modified, leak-free manikin. Resuscitation parameters were recorded using a self-inflatable bag PPV with an Intersurgical anatomical air cushion rim face mask (IS) and a size 0/1 Laerdal round face mask. Three different positions of the IS were tested: correct position, 90° and 180° rotation in reference to the midline of the face. IS masks in each correct position on the face but with different inflation of the air cushion (empty, 10, 20 and 30 mL). Mask leak was similar with mask rotation to either 90° or 180° but significantly increased from 27 (13-73) % with an adequate filled IS mask compared to 52 (16-83) % with an emptied air cushion rim. CONCLUSION: Anatomical-shaped face mask had similar mask leaks compared to round face mask. A wrongly positioned anatomical-shaped mask does not influence mask leak. Mask leak significantly increased once the air cushion rim was empty, which may cause failure in mask PPV.