Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Assessing lung aeration using ultrasound after birth in near-term lambs at risk of respiratory distress

BackgroundOptimizing respiratory support after birth requires real-time feedback on lung aeration. We hypothesized that lung ultrasound (LUS) can accurately monitor the extent and progression of lung aeration after birth and is closely associated with oxygenation.MethodsNear-term (140 days gestation, term ∼147 days), spontaneously breathing lambs with normal (controls; n = 10) or elevated lung liquid levels (EL; n= 9) were delivered by Caesarean section and monitored for four hours after birth. LUS (Phillips CX50, L3–12 transducer) images and arterial blood gases were taken every 5–20 min. LUS images were analyzed both qualitatively (grading) and quantitatively (using the coefficient of variation of pixel intensity (CoV) to estimate the degree of lung aeration), which was correlated with the oxygen exchange capacity of the lungs (Alveolar-arterial difference in oxygen; AaDO2).ResultsLung aeration, measured using LUS, and the AaDO2 improved over the first 4 h after birth. The increase in lung aeration measured using CoV of pixel intensity, but not LUS grade, was significantly reduced in EL lambs compared to controls (p = 0.02). The gradual decrease in AaDO2 after birth was significantly correlated with increased lung aeration in both control (grade, r2 = 0.60, p < 0.0001; CoV, r2 = 0.54, p < 0.0001) and EL lambs (grade, r2 = 0.51, p < 0.0001; CoV, r2 = 0.44, p < 0.0001).ConclusionsLUS can monitor lung aeration and liquid clearance after birth in spontaneously breathing near-term lambs. Image analysis techniques (CoV) may be able detect small to moderate differences in lung aeration in conditions with lung liquid retention which are not readily identified using qualitative LUS grading

Synergy between trastuzumab and pertuzumab for human epidermal growth factor 2 (Her2) from colocalization: an in silico based mechanism

10.1186/bcr2888Breast Cancer Research133-BCRR

Increased end-expiratory pressures improve lung function in near-term newborn rabbits with elevated airway liquid volume at birth

Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmH(2)O on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (similar to 7 mL/kg, control, n = 11) or cesarean section (similar to 37 mL/kg; elevated liquid (EL), n = 11] were mechanically ventilated (tidal volume= 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmH(2)O (control, n = 6; EL, n = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmH(2)O (control, n = 5; EL, n = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmH(2)O PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmH(2)O PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress.NEW & NOTEWORTHY Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory distress. We showed that respiratory support with an end-expiratory pressure supports lung function in near-term rabbits with elevated airway liquid volumes at birth. This study provides further physiological understanding of lung function in newborns with elevated airway liquid volumes at risk of respiratory distress.Developmen

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Sustainable Luxury Marketing : A synthesis and research agenda

Sustainability has become a pervasive issue for the luxury sector, gaining traction with brand managers, scholars, policy-makers, the media, and academia. The purpose of this paper is to examine the state of sustainable luxury research in marketing and consumer behaviour by critically reviewing and synthesizing the growing but fragmented body of scholarly work on sustainable-luxury marketing. The paper critically assesses where, how and by whom research on sustainable luxury is being conducted, and it identifies gaps for future investigation. The paper reviews research published between 2007 and 2018 within major peer-reviewed English-language scholarly publications in business, marketing, ethics, fashion, food and tourism journals. The research is identified using the keywords sustainable luxury, green luxury, eco-luxury and organic luxury. Three core themes emerge from this review: (1) consumer concerns and practices; (2) organizational concerns and practices; and (3) international and cross-cultural issues. The review confirms that research on sustainable luxury is significantly underdeveloped. This paper provides the first critical and comprehensive assessment and categorization of the emergent literature streams on sustainable luxury. The authors argue for a broader, deeper and more critical research agenda on the relationship between sustainability and luxury. Potential avenues for future research on sustainable luxury are proposed, with calls for theoretical and cross-cultural reflections that tackle broader systemic and institutional issues within the field

Increased lung prolyl hydroxylase and decreased glucocorticoid receptor are related to decreased surfactant protein in the growth-restricted sheep fetus

Published 1 July 2015Experimental placental restriction (PR) by carunclectomy in fetal sheep results in intrauterine growth restriction (IUGR), chronic hypoxemia, increased plasma cortisol, and decreased lung surfactant protein (SP) expression. The mechanisms responsible for decreased SP expression are unknown but may involve decreased glucocorticoid (GC) action or changes in hypoxia signaling. Endometrial caruncles were removed from nonpregnant ewes to induce PR. Lungs were collected from control and PR fetuses at 130-135 (n = 19) and 139-145 (n = 28) days of gestation. qRT-PCR and Western blotting were used to quantify lung mRNA and protein expression, respectively, of molecular regulators and downstream targets of the GC and hypoxia-signaling pathways. We confirmed a decrease in SP-A, -B, and -C, but not SP-D, mRNA expression in PR fetuses at both ages. There was a net downregulation of GC signaling with a reduction in GC receptor (GR)-α and -β protein expression and a decrease in the cofactor, GATA-6. GC-responsive genes including transforming growth factor-β1, IL-1β, and β2-adrenergic receptor were not stimulated. Prolyl hydroxylase domain (PHD)2 mRNA and protein and PHD3 mRNA expression increased with a concomitant increase in hypoxia-inducible factor-1α (HIF-1α) and HIF-1β mRNA expression. There was an increase in mRNA expression of several, but not all, hypoxia-responsive genes. Hence, both GC and hypoxia signaling may contribute to reduced SP expression. Although acute hypoxia normally inactivates PHDs, chronic hypoxemia in the PR fetus increased PHD abundance, which normally prevents HIF signaling. This may represent a mechanism by which chronic hypoxemia contributes to the decrease in SP production in the IUGR fetal lung.Sandra Orgeig, Erin V. McGillick, Kimberley J. Botting, Song Zhang, I. Caroline McMillen, and Janna L. Morriso

Differential effects of late gestation maternal overnutrition on the regulation of surfactant maturation in fetal and postnatal life

Key points: •Offspring of overweight and obese women are at greater risk for respiratory complications at birth. •We determined the effect of late gestation maternal overnutrition (LGON) in sheep on surfactant maturation, glucose transport and fatty acid metabolism in the lung in fetal and postnatal life. •There were significant decreases in surfactant components and numerical density of surfactant producing cells in the alveolar epithelium due to LGON in the fetal lung. However, there were no differences in the levels of these surfactant components between control and LGON lambs at 30 days of age. •The reduced capacity for surfactant production in fetuses as a result of LGON may affect the transition to air breathing at birth. •There was altered glucose transport and fatty acid metabolism in the lung as a result of LGON in postnatal life. However, there is a normalisation of surfactant components that suggests accelerated maturation in the lungs after birth. Abstract: With the increasing incidence of obesity worldwide, the proportion of women entering pregnancy overweight or obese has increased dramatically. The fetus of an overnourished mother experiences numerous metabolic changes that may modulate lung development and hence successful transition to air breathing at birth. We used a sheep model of maternal late gestation overnutrition (LGON; from 115 days' gestation, term 147 ± 3 days) to determine the effect of exposure to an increased plane of nutrition in late gestation on lung development in the fetus (at 141 days' gestation) and the lamb (30 days after birth). We found a decrease in the numerical density of surfactant protein positive cells, as well as a reduction in mRNA expression of surfactant proteins (SFTP-A, -B and -C), a rate limiting enzyme in surfactant phospholipid synthesis (phosphate cytidylyltransferase 1, choline, α; PCYT1A), and glucose transporters (SLC2A1 and SLC2A4) in the fetal lung. In lambs at 30 days after birth, there were no differences between Control and LGON groups in the surfactant components that were downregulated in the LGON fetuses. However, mRNA expression of SFTP-A, PCYT1A, peroxisome proliferator activated receptor-γ, fatty acid synthase and fatty acid transport protein were increased in LGON lambs compared to controls. These results indicate a reduced capacity for surfactant production in late gestation. While these deficits are normalised by 30 days after birth, the lungs of LGON lambs exhibited altered glucose transport and fatty acid metabolism, which is consistent with an enhanced capacity for surfactant synthesis and restoration of surfactant maturity in these animals.Mitchell C. Lock , Erin V. McGillick, Sandra Orgeig, I. Caroline McMillen, Beverly S. Mühlhäusler, Song Zhang and Janna L. Morriso

High vs. Low Initial Oxygen to Improve the Breathing Effort of Preterm Infants at Birth: Study Protocol for a Randomized Controlled Trial

Developmen