Gas Exchange Function Research Articles

Rapid hydraulic recovery in Eucalyptus pauciflora after drought: linkages between stem hydraulics and leaf gas exchange

In woody plants, photosynthetic capacity is closely linked to rates at which the plant hydraulic system can supply water to the leaf surface. Drought-induced embolism can cause sharp declines in xylem hydraulic conductivity that coincide with stomatal closure and reduced photosynthesis. Recovery of photosynthetic capacity after drought is dependent on restored xylem function, although few data exist to elucidate this coordination. We examined the dynamics of leaf gas exchange and xylem function in Eucalyptus pauciflora seedlings exposed to a cycle of severe water stress and recovery after re-watering. Stomatal closure and leaf turgor loss occurred at water potentials that delayed the extensive spread of embolism through the stem xylem. Stem hydraulic conductance recovered to control levels within 6 h after re-watering despite a severe drought treatment, suggesting an active mechanism embolism repair. However, stomatal conductance did not recover after 10 d of re-watering, effecting tighter control of transpiration post drought. The dynamics of recovery suggest that a combination of hydraulic and non-hydraulic factors influenced stomatal behaviour post drought.

Chorioallantoic Placentation in Viperid Snakes

Chorioallantoic Placentation in Viperid Snakes

Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor

SUMMARYCo-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung 1. In this report, we show that the pulmonary vasculature develops even in the absence of lung development. We have identified a population of multi-potent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2/Gli1/Isl1. We show that CPPs arise from cardiac progenitors prior to lung development. Lineage tracing and clonal analysis demonstrates that CPPs generate the mesoderm lineages within the cardiac inflow tract and lung including cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression from the foregut endoderm, which is required for connection of the pulmonary vasculature to the heart. Together, these studies identify a novel population of multipotent cardiopulmonary progenitors that coordinates heart and lung co-development that is required for adaptation to terrestrial existence.

Combined Pulmonary and Renal Support in a Single Extracorporeal Device

Combined acute lung injury (ALI) and kidney injury (AKI) is a common problem in critically ill patients. By combining pulmonary (gas exchange) and renal (hemofiltration) support in one extracorporeal device with low-flow resistance, we seek to provide less artificial surfaces maintaining sufficient organ support. Modified Interventional Lung Assist (iLA) Membrane Ventilator (miLA), consisting of polymethylpentene gas exchange membranes and polyethersulfone hemofiltration membranes, was compared in vitro with the original iLA design, consisting only of gas exchange membranes, regarding both delivery volume and loss in pressure versus pump rate. Efficiency tests concerning gas exchange and hemofiltration rate were performed in vitro and in vivo. In vitro analyses showed no differences between both systems, with adequate filtration rates in miLA. Anticoagulation and constant blood pressure allowed 1.2 L/min of blood flow and hemofiltration rates of 70 ml/h through miLA in vivo. No major differences between concentrations of filtered molecules in blood and hemofiltrate were found. A stable gas exchange function was maintained. No signs of hemolysis were detected. Our results confirm the feasibility of single-device support for combined pulmonary and renal injury. Novel devices expanding on this concept may potentially improve therapy of critically ill patients with ALI/AKI.

A feedback loop in PPARγ–adenosine A2A receptor signaling inhibits inflammation and attenuates lung damages in a mouse model of LPS-induced acute lung injury

Although peroxisome proliferator-activated receptor-γ (PPARγ) and adenosine A2A receptor (A2AR) are reported to be anti-inflammatory factors in acute lung injury (ALI), their internal link and synergic or antagonistic effect after activation are poorly understood. Here, we found that PPARγ and A2AR could upregulate the mRNA and protein expressions of each other in lung tissues of LPS-induced mouse ALI model and murine macrophages. Further investigation demonstrated that PPARγ upregulated A2AR expression by directly binding to a DR10 response element (−218 to −197) within A2AR gene promoter region. Instead of directly interacting with PPARγ, A2AR stimulated PPARγ expression via protein kinase A (PKA)–cAMP response element binding protein (CREB) signaling by provoking the binding of CREB to a cAMP responsive element (CRE)-like site in PPARγ gene promoter region. In addition, combination of PPARγ and A2AR agonists was found to exert obviously better effect on suppressing neutrophil infiltration and inflammatory cytokine expressions, attenuating lung edema, pathological changes and improving lung function of blood gas exchange than their single application. These findings reveal a novel functional positive feedback loop between PPARγ and A2AR signaling to potentialize their effect on inhibiting inflammation and attenuating lung damages in ALI. It suggests that targeting this PPARγ–A2AR signaling rather than PPARγ or A2AR alone may be a more attractive and efficient potential therapeutic strategy for ALI.

Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome

Surfactant (SF) instillation may produce acute deleterious effects on gas exchange and both systemic and cerebral hemodynamics. Our aim was to compare the effects of aerosolized SF (SF-aero) with those of bolus SF (SF-bolus) administration on gas exchange, lung mechanics, and cardiovascular function in premature lambs with respiratory distress syndrome (RDS). Fourteen preterm lambs (85% gestation) were randomly assigned to receive SF-aero or SF-bolus. Oxygenation index (OI), PaCO2, cardiovascular parameters, carotid blood flow (CBF), lung compliance (mean dynamic compliance), and tidal volume (VT) were measured every 30 min for 6 h. Biochemical and histological analyses were performed. After delivery, lambs developed severe RDS (inspiratory fraction of oxygen: 1; pH < 7.15; PaCO2 > 80 mm Hg; PaO2 < 30 mm Hg, mean dynamic compliance < 0.08 ml/cm H2O/kg). By 60 min after treatment, both groups showed an improvement in OI, PaCO2, mean dynamic compliance, and VT that was maintained until the end of the experiment. PaCO2 and CBF increased significantly in the SF-bolus group during the first 15-30 min, without concomitant changes in cardiovascular parameters, whereas in the SF-aero group, PaCO2 and CBF decreased gradually. SF-aero induced less alveolar hemorrhage and inflammation. SF-aero produced improvements in gas exchange and lung mechanics similar to those produced by bolus administration but with less lung injury and fewer cerebral hemodynamic changes.

Editorial Comment: Expanding lung donation: the use of uncontrolled non-heart beating donors

cadaver up to six hours after cardiac arrest. J Heart Lung Transplant 1999;18:582–6. [19] Wierup P, Bolys R, Steen S. Gas exchange function one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver after failed resuscitation. J Heart Lung Transplant 1999;18:133–8. [20] Steen S, Kimblad PO, Sjoberg T, Lindberg L, Ingemansson R, Massa G. Safe lung preservation for twenty-four hours with Perfadex. Ann Thorac Surg 1994;57:450–7. [21] Marasco SF, Bailey M, McGlade D, Snell G, Westall G, Oto T et al. Effect of donor preservation solution and survival in lung transplantation. J Heart Lung Transplant 2011;30:414–9. [22] Okazaki M, Date H, Inokawa H, Okutani D, Aokage K, Nagahiro I et al. Optimal time for post-mortem heparinization in canine lung transplantation with non-heart-beating donors. J Heart Lung Transplant 2006;25: 454–60. [23] Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011;364:1431–40.

Comparative analysis of gas exchange and cardiorespiratory system responses of swimmers and skiers to increasing normobaric hypoxia and physical load

Qualification-comparable groups of young men engaged in cyclic kinds of sports were tested using a stepwise increasing load on a bicycle ergometer and 25-min exponentially increasing normobaric hypoxia to a final oxygen concentration of 10%. Skiers, who had the greatest values of maximal oxygen consumption during muscular work, showed relaxed cardiorespiratory reactions and a greater decrease in hemoglobin saturation with oxygen in hypoxia. Swimmers, whose ventilatory function in the course of trainings was restricted, developed preadaptation to hypoxia, with changes in external respiration and gas exchange functions, which allowed better saturation of blood with oxygen in lungs during hypoxia. The joint assessment of the aerobic capacity during physical work and physiological responses to hypoxia showed a direct correlation between the individual maximal oxygen consumption and the rate of decrease in the blood hemoglobin saturation in increasing hypoxia, which may be promising for assessing the functional state of athletes and its correction during training.

Effect of 1-MCP on Gas Exchange and Carbohydrate Concentrations of the Cotton Flower and Subtending Leaf under Water-Deficit Stress

Ethylene is an endogenous plant hormone that increases under adverse environmental conditions, resulting in leaf and fruit abscission and ultimately yield reduction. In cotton, however, the effects of water-deficit stress on ethylene production have been uncertain. In this study it was hypothesized that application of an ethylene inhibitor 1-Methylcyclo- propene (1-MCP) would prevent ethylene production and result in alleviation of water-deficit stress consequences on the physiology and metabolism of the cotton flower and subtending leaf. To test this hypothesis, growth chamber experiments were conducted in 2009-2010 with treatments consisting of (C) untreated well-watered control, (C + 1MCP) well-watered plus 1-MCP, (WS) untreated water-stressed control, and (WS + 1MCP) water-stressed plus 1-MCP. The plants were subjected to two consecutive drying cycles during flowering, approximately 8 weeks after planting, and 1-MCP was foliar applied at a rate of 10g. ai/ha at the beginning of each drying cycle. The results showed that 1-MCP application had no significant effect on gas exchange functions and did not prevent reductions from water stress in leaf photosynthesis, respiration and stomatal conductance. However, application of 1-MCP resulted in a decrease in sucrose content of water-stressed pistils compared to the control indicating that 1-MCP has the potential to interfere in carbohydrate metabolism of reproductive units.

Alveolar Gas Exchange and Pulmonary Functions in Patients with Type II Diabetes Mellitus.

The incidence of diabetes is increasing tremendously throughout the world especially in the developing countries. This disease affects various organs like eyes, nerves, kidneys and the heart. In this study, we investigated whether lungs are also one of the target organs of diabetes mellitus or not. To assess the pulmonary function parameters including alveolar gas exchange in patients with Type 2 Diabetes mellitus and to find the influence of hyperglycaemia and duration of diabetes. This cross sectional study involved 30 type II diabetic patients of age 30-60 years attending the diabetic outpatient department of SRM Medical College & Research Centre and 30 age and sex matched non-diabetic subjects as controls. The glycated haemoglobin (HbA1c) levels, fasting and post prandial blood glucose levels, pulmonary function parameters such as Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Forced Expiratory Volume Percentage (FEV1 /FVC), Peak Expiratory Flow Rate (PEFR), Forced Expiratory Flow (25 - 75%), Peak Inspiratory flow ( PIF), Forced Inspiratory Vital Capacity ( FIVC), Total Lung Capacity ( TLC),Diffusing capacity of lung for carbon monoxide( DLCO) were measured for all the participants using Easyone Pro computerised spirometer. DLCO was measured by single breath Carbon Monoxide (CO) diffusion test. The alveolar membrane permeability was assessed by evaluating the ratio of DLCO to Alveolar Ventilation (VA). The pulmonary function parameters FVC, FEV1, PEFR, PIF, FIVC, TLC , DLCO and DLCO/VA were significantly low (p<0.05) in patients with type II diabetes mellitus when compared to control group. The DLCO and DLCO/VA were significantly lower (p<0.05) in patients with poor glycemic control(HbA1c > 7). We conclude that the pulmonary function parameters like FVC, FEV1, PEFR, PIF, FIVC, TLC and alveolar gas exchange were significantly reduced in patients with type II diabetes. The patients with Type II diabetes mellitus had a restrictive pattern of respiratory abnormality. The patients with poor glycaemic control( HbA1c > 7) had reduced alveolar diffusion which was not dependent on the duration of diabetes. The impaired respiratory function may give way for the development of pulmonary complications. Spirometry can be used as a screening tool among diabetics as an early preventive measure.

J024021 鼓室換気能評価装置の開発([J024-02]音・光とバイオメカニクス)

Pneumatization of the middle ear cavity is associated with the transmucosal gas exchange function of the middle ear cavity and the eustachian tube function. In some cases, the tympanic membrane is gradually depressed by negative pressure of the middle ear cavity due to shortage of ventilation. As a result, the depressed tympanic membrane leads to adhesive otitis. Ventilation of tympanic cavity is important for medical treatments of adhesive otitis. The function of ventilation may be evaluated by measuring the volume of the middle ear cavity in addition to the eustachian tube function. In this research, the equipment for evaluating the function of ventilation in tympanic cavity was developed. In evaluation experiment of the equipment using an artificial ear model, the volumetric error of the ear model was 5% or less. In clinical measurement, the equipment was operated by medical doctors, and the volume of the middle ear cavity was able to be determined, and the function of the Eustachian tube was able to be evaluated.

Improvement of eustachian tube function by tissue‐engineered regeneration of mastoid air cells

Objectives/HypothesisMost cases of chronic otitis media (OMC) are associated with poor development of the mastoid air cells (MACs) and poor Eustachian tube (ET) function. We have previously reported that MAC regeneration can effectively eliminate intractable OMC. In this study, we assessed the ability of regenerated MACs to restore normal gas exchange function and contribute to improved ET function.Study DesignClinical trial with control.SettingGeneral hospitals.Materials and MethodsSeventy-six patients with OMC, including cholesteatoma and adhesive otitis media, received tympanoplasty and MAC regeneration therapy. At the first-stage of tympanoplasty, artificial pneumatic bones and/or autologous bone fragments were implanted into the opened mastoid cavity. At the 2nd-stage operation, a nitrous oxide (N2O) gas study was performed in 10 patients to measure middle ear pressure (MEP). For the control group, MEP was measured in five patients with good MAC development during cochlear implantation or facial nerve decompression. ET function was measured twice in each patient, once before the 1st operation and 6 months after the second operation.ResultsAt the 2nd-stage operation, in all cases with regenerated MACs and in the normal control group, MEP changed after administration of N2O. In contrast, no change in MEP was observed in cases with unregenerated MACs. In 70% (n = 37/53) of the regenerated MAC group, ET function was improved, whereas improvement of ET function was observed in only 13% (n = 3/23) of the unregenerated MAC group.ConclusionsTissue-engineered regeneration of MACs improves ET function and gas exchange in the middle ear. Laryngoscope, 2012Level of Evidence3b

Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant.

Genome‐scale study of transcription factor expression in the branching mouse lung

Mammalian lung development consists of a series of precisely choreographed events that drive the progression from simple lung buds to the elaborately branched organ that fulfills the vital function of gas exchange. Strict transcriptional control is essential for lung development. Among the large number of transcription factors encoded in the mouse genome, only a small portion of them are known to be expressed and function in the developing lung. Thus a systematic investigation of transcription factors expressed in the lung is warranted. To enrich for genes that may be responsible for regional growth and patterning, we performed a screen using RNA in situ hybridization to identify genes that show restricted expression patterns in the embryonic lung. We focused on the pseudoglandular stage during which the lung undergoes branching morphogenesis, a cardinal event of lung development. Using a genome-scale probe set that represents over 90% of the transcription factors encoded in the mouse genome, we identified 62 transcription factor genes with localized expression in the epithelium, mesenchyme, or both. Many of these genes have not been previously implicated in lung development. Our findings provide new starting points for the elucidation of the transcriptional circuitry that controls lung development.

Engineered Vascular Beds Provide Key Signals to Pancreatic Hormone-Producing Cells

The mechanisms underlying early islet graft failure are not entirely clear, but are thought to involve ischemic injury due to delayed vascularization. We hypothesize that blood vessels play an active role in cell-cell communications supporting islet survival and engraftment. To test this hypothesis and to uncouple endothelial cell (EC)-generated signaling stimuli from their nutritional and gas exchange functions, we developed three dimensional (3D) endothelial vessel networks in engineered pancreatic tissues prepared from islets, fibroblasts and ECs. The tri-culture setup, seeded on highly porous biocompatible polymeric scaffolds closely mimics the natural anatomical context of pancreatic vasculature. Enhanced islet survival correlating with formation of functional tube-like endothelial vessels was demonstrated. Addition of foreskin fibroblasts to islet-endothelial cultures promoted tube-like structure formation, which further supported islet survival as well as insulin secretion. Gene expression profiles of EC growth factors, extracellular matrix (ECM), morphogenes and differentiation markers were significantly different in 2D versus 3D culture systems and were further modified upon addition of fibroblasts. Implantation of prevascularized islets into diabetic mice promoted survival, integration and function of the engrafted engineered tissue, supporting the suggested role of ECs in islet survival. These findings present potential strategies for preparation of transplantable islets with increased survival prospects.

Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function.

Signaling Networks Regulating Development of the Lower Respiratory Tract

The lungs serve the primary function of air-blood gas exchange in all mammals and in terrestrial vertebrates. Efficient gas exchange requires a large surface area that provides intimate contact between the atmosphere and the circulatory system. To achieve this, the lung contains a branched conducting system (the bronchial tree) and specialized air-blood gas exchange units (the alveoli). The conducting system brings air from the external environment to the alveoli and functions to protect the lung from debris that could obstruct airways, from entry of pathogens, and from excessive loss of fluids. The distal lung enables efficient exchange of gas between the alveoli and the conducting system and between the alveoli and the circulatory system. In this article, we highlight developmental and physiological mechanisms that specify, pattern, and regulate morphogenesis of this complex and essential organ. Recent advances have begun to define molecular mechanisms that control many of the important processes required for lung organogenesis; however, many questions remain. A deeper understanding of these molecular mechanisms will aid in the diagnosis and treatment of congenital lung disease and in the development of strategies to enhance the reparative response of the lung to injury and eventually permit regeneration of functional lung tissue.

Impact of Detoxification Techniques on Pulmonary Gas Exchange Function in Patients with Generalized Peritonitis

Objective: to analyze the impact of different detoxification techniques on pulmonary gas exchange function in patients with generalized peritonitis complicated by multiple organ failure. Subjects and methods. One hundred and thirty patients with generalized peritonitis were examined. According to the used detoxification techniques, the patients were divided into 5 groups. All the patients underwent a comprehensive examination, the key element of which was the evaluation of gas exchange parameters. Results. Membrane plasmapheresis and plasmapheresis with sodium hypochlorite infusion to the plasma filter in patients with peritonitis are shown to improve pulmonary blood oxygenation.

Alveolar type II cell‐specific deletion of p120‐catenin in mice demonstrates the crucial role of Type II cell‐localized p120‐ catenin in regulating alveolar epithelial barrier function

Maintenance of alveolar epithelial barrier integrity is essential for normal alveolar gas exchange function and lung fluid balance. The normal alveolar epithelium is composed of two types of cells: flat type I cells comprising ~95% of the gas‐exchange surface, and cuboidal type II cells, which secrete surfactant. Type II cells also function as facultative progenitor cells in that they can proliferate and trans‐differentiate into type I cells during homeostasis as well as post alveolar epithelial injury. However, molecular mechanisms of maintenance and repair of alveolar barrier are not clear. p120‐ catenin is located at epithelial adherens junction (AJ) where is required for stabilizing E‐Cadherin. Here we addressed whether p120‐catenin contributes to alveolar barrier function in lung. We made an alveolar type II cell specific p120‐Catenin knock‐out mouse line. These mice displayed a persistently leaky alveolar barrier and low grade pulmonary edema and chronic lung inflammation characterized by infiltration of inflammatory cells. These findings indicate that while type II cells make up only 5% of alveolar epithelial surface area, type II cell p120‐catenin plays a critical role in maintenance of alveolar epithelial barrier and homeostasis.

Morphological and functional characterization of a novel Na+/K+-ATPase-immunoreactive, follicle-like structure on the gill septum of Japanese banded houndshark, Triakis scyllium

In teleost fishes, it is well-established that the gill serves as an important ionoregulatory organ in addition to its primary function of respiratory gas exchange. In elasmobranch fish, however, the ionoregulatory function of the gills is still poorly understood. Although mitochondria-rich (MR) cells have also been found in elasmobranch fish, these cells are considered to function primarily in acid-base regulation. In this study, we found a novel aggregate structure made up of cells with basolaterally-expressed Na(+)/K(+)-ATPase (NKA), in addition to NKA-immunoreactive MR cells that have already been described in the gill filament and lamella. The cell aggregates, named follicularly-arranged NKA-rich cells (follicular NRCs), were found exclusively in the epithelial lining of the venous web in the cavernous region of the filament and the inter-filamental space of the gill septum. The follicular NRCs form a single-layered follicular structure with a large lumen leading to the external environment. The follicular NRCs were characterized by: (i) well-developed microvilli on the apical membrane, (ii) less prominent infoldings of the basolateral membrane and (iii) typical junction structures including deep tight junction between cells. In addition, large numbers of vesicles were observed in the cytoplasm and some of them were fused to the lateral membrane. The follicular NRCs expressed Na(+)/H(+) exchanger 3 and Ca(2+) transporter 1. The follicular NRCs thus have the characteristics of absorptive ionoregulatory cells and this suggests that the elasmobranch gill probably contributes more importantly to body fluid homeostasis than previously thought.