scholarly journals Lymphatic function is required prenatally for lung inflation at birth

2014 ◽  
Vol 211 (5) ◽  
pp. 815-826 ◽  
Author(s):  
Zoltán Jakus ◽  
Jason P. Gleghorn ◽  
David R. Enis ◽  
Aslihan Sen ◽  
Stephanie Chia ◽  
...  

Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants.

2020 ◽  
Vol 142 (10) ◽  
Author(s):  
Laurel E. Schappell ◽  
Daniel J. Minahan ◽  
Jason P. Gleghorn

Abstract Premature birth interrupts the development of the lung, resulting in functional deficiencies and the onset of complex pathologies, like bronchopulmonary dysplasia (BPD), that further decrease the functional capabilities of the immature lung. The dysregulation of molecular targets has been implicated in the presentation of BPD, but there is currently no method to correlate resultant morphological changes observed in tissue histology with these perturbations to differences in function throughout saccular and alveolar lung development. Lung compliance is an aggregate measure of the lung's mechanical properties that is highly sensitive to a number of molecular, cellular, and architectural characteristics, but little is known about compliance in the neonatal mouse lung due to measurement challenges. We have developed a novel method to quantify changes in lung volume and pressure to determine inspiratory and expiratory compliance throughout neonatal mouse lung development. The compliance measurements obtained were validated against compliance values from published studies using mature lungs following enzymatic degradation of the extracellular matrix (ECM). The system was then used to quantify changes in compliance that occurred over the entire span of neonatal mouse lung development. These methods fill a critically important gap connecting powerful mouse models of development and disease to measures of functional lung mechanics critical to respiration and enable insights into the genetic, molecular, and cellular underpinnings of BPD pathology to improve lung function in premature infants.


1986 ◽  
Vol 60 (5) ◽  
pp. 1610-1614 ◽  
Author(s):  
A. J. Lechner ◽  
D. C. Winston ◽  
J. E. Bauman

Prenatal starvation in the guinea pig causes reduced pulmonary diffusing capacity and retarded alveolarization among neonates. To study the impact of such starvation on biochemical and mechanical properties of the neonatal lung, pregnant guinea pigs were fed ad libitum throughout gestation or starved with 50% rations during their last trimester. Neonatal body weight was 35% less due to starvation, and dry lung weight, DNA, and protein contents were decreased 26, 36, and 31%, respectively (P less than 0.001 for all). Hematological data indicated no anemia, hypoproteinemia, or altered glucocorticoid levels due to starvation. Total surfactant phospholipids in these neonates were reduced 61% in lavage and 35% in the neonatal lung tissue, although surfactant compositions were similar to controls. Specific lung compliance in the air-filled lungs was not altered, but the saline-filled lungs were more distensible over deflation pressures of 9–18 cmH2O (transpulmonary). Although starvation retarded both lung cellularity and surfactant, only that portion of lung elastic recoil attributable to tissue forces was affected.


HNO ◽  
2021 ◽  
Author(s):  
Patrick J. Schuler ◽  
Jens Greve ◽  
Thomas K. Hoffmann ◽  
Janina Hahn ◽  
Felix Boehm ◽  
...  

Abstract Background One of the main symptoms of severe infection with the new coronavirus‑2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate. Objective Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19. Study design Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital. Patients Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation. Measurements Clinical and ventilation data were obtained from medical records in a retrospective manner. Results A total of 18 patients with confirmed SARS-CoV‑2 infection and surgical tracheostomy were analyzed. The age range was 42–87 years. All patients received open tracheostomy between 2–16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR). Conclusion Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel.


2009 ◽  
Vol 117 (3) ◽  
pp. 129-138 ◽  
Author(s):  
Emily M. Segar ◽  
Andrew W. Norris ◽  
Jian-Rong Yao ◽  
Shanming Hu ◽  
Stacia L. Koppenhafer ◽  
...  

ODM (offspring of diabetic mothers) have an increased risk of developing metabolic and cardiovascular dysfunction; however, few studies have focused on the susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg of body weight, intraperitoneally) in pregnant rats on gestational day 13 and was partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (P<0.05); however, by 6 months of age this trend had reversed. A euglycaemic–hyperinsulinamic clamp revealed insulin resistance in male ODM (P<0.05). In 6–8-month-old female ODM, aortas had significantly enhanced contractility in response to KCl, ET-1 (endothelin-1) and NA (noradrenaline). No differences in responses to ET-1 and NA were apparent with co-administration of L-NNA (NG-nitro-L-arginine). Relaxation in response to ACh (acetylcholine), but not SNP (sodium nitroprusside), was significantly impaired in female ODM. In contrast, males had no between-group differences in response to vasoconstrictors, whereas relaxation to SNP and ACh was greater in ODM compared with control animals. Thus the development of diabetes during pregnancy programmes gender-specific insulin resistance and vascular dysfunction in adult offspring.


Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 794
Author(s):  
Marco Aurelio Sartim ◽  
Camila O. S. Souza ◽  
Cassiano Ricardo A. F. Diniz ◽  
Vanessa M. B. da Fonseca ◽  
Lucas O. Sousa ◽  
...  

Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.


CHEST Journal ◽  
2021 ◽  
Vol 160 (4) ◽  
pp. A1095
Author(s):  
Lauren Abplanalp ◽  
Girish Balachandran Nair ◽  
Enrique Calvo Ayala ◽  
Limin Yu

2016 ◽  
Vol 32 (7) ◽  
pp. 421-428 ◽  
Author(s):  
Telma C. A. Sequeira ◽  
Ahmed S. BaHammam ◽  
Antonio M. Esquinas

Obesity is a global epidemic that adversely affects respiratory physiology. Sleep-disordered breathing and obesity hypoventilation syndrome (OHS) are among the most common pulmonary complications related to obesity class III. Patients with OHS may present with acute hypercapnic respiratory failure (AHRF) that necessitates immediate noninvasive ventilation (NIV) or invasive ventilation and intensive care unit (ICU) monitoring. The OHS is underrecognized as a cause of AHRF. The management of mechanical ventilation in obese ICU patients is one of the most challenging problems facing respirologists, intensivists, and anesthesiologists. The treatment of AHRF in patients with OHS should aim to improve alveolar ventilation with better alveolar gas exchange, as well as maintaining a patent upper airway, which is ideally achieved through NIV. Treatment with NIV is associated with improvement in blood gases and lung mechanics and may reduce hospital admissions and morbidity. In this review, we will address 3 main issues: (1) NIV of critically ill patients with acute respiratory failure and OHS; (2) the indications for postoperative application of NIV in patients with OHS; and (3) the impact of OHS on weaning and postextubation respiratory failure. Additionally, the authors propose an algorithm for the management of obese patients with AHRF.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.


1963 ◽  
Vol 18 (5) ◽  
pp. 881-887 ◽  
Author(s):  
H. J. H. Colebatch ◽  
D. F. J. Halmagyi

In sheep, anesthetized and intubated, bilateral cervical vagotomy produced no change in lung compliance (Cl), reduced inspiratory resistance to airflow, increased expiratory resistance to airflow, and changed the pattern of breathing. Electrical stimulation of the peripheral end of the cut vagus nerve produced an immediate increase in lung volume due to an increase in inspiratory tonus, a fall in Cl, an increase in resistance to airflow, and a decrease in heart rate and systemic arterial pressure. Pulmonary arterial pressure remained unchanged; pulmonary arterial resistance increased. These effects were blocked by atropine. The lung mechanics changes were partly reversed spontaneously, completely reversed by forced inflation, and potentiated by prostigmine. The effects on lung mechanics suggest that vagal stimulation in the sheep mainly affects the peripheral airways producing airway closure, and indicates the possibility of a nervous mechanism for the control of the number of ventilated lung units. compliance; total pulmonary resistance; inspiratory; tonus; peripheral airway reaction; respiratory pattern Submitted on December 6, 1962


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