Site Of Gas Exchange Research Articles

Discontinuous, biphasic, ontogenetic shifts in the metabolic allometry of aquatic animals?

Several investigations in recent years have reported patterns of discontinuous, biphasic, loglinear variation in the metabolic allometry of aquatic animals. These putative shifts in pattern of allometry have been attributed to changes in the primary site for gas exchange from cutaneous to branchial as animals undergo ontogenetic changes in size, shape, and surface area. Because of the important implications of the earlier research with regard to both physiology and evolution, I re-examined data that purportedly support claims of discontinuous, biphasic allometry in oxygen consumption versus body size of American eels (Anguilla rostrata) and spiny lobsters (Sagmariasus verreauxi). I used ANCOVA to fit three different statistical models to each set of logarithmic transformations and then assessed the fits by Akaike's Information Criterion. The observations for both species were described better by a single straight line fitted to the full distribution than by a biphasic model. Eels, lobsters, and other aquatic animals undergo changes in shape and surface area as they grow, but such changes are not necessarily accompanied by changes in the pattern of metabolic allometry.

Respiratory and population effects of e-cigarettes: A Chinese perspective.

Respiratory and population effects of e-cigarettes: A Chinese perspective.

Engineering Dynamic 3D Models of Lung.

The lung parenchyma-consisting of gas-filled alveoli, vasculature, and connective tissue-is the site for gas exchange in the lung and plays a critical role in a number of chronic lung diseases. In vitro models of lung parenchyma can, therefore, provide valuable platforms for the study of lung biology in health and disease. Yet modeling such a complex tissue requires integrating multiple components, including biochemical cues from the extracellular environment, geometrically defined multicellular interactions, and dynamic mechanical inputs such as the cyclic stretch of breathing. In this chapter, we provide an overview of the broad spectrum of model systems that have been developed to recapitulate one or more features of lung parenchyma, and some of the scientific advances generated by those models. We discuss the use of both synthetic and naturally derived hydrogel materials, precision-cut lung slices, organoids, and lung-on-a-chip devices, with perspectives on the strengths, weaknesses, and potential future directions of these engineered systems.

Ion regulation at gills precedes gas exchange and the origin of vertebrates.

Gas exchange and ion regulation at gills have key roles in the evolution of vertebrates1-4. Gills are hypothesized to have first acquired these important homeostatic functions from the skin in stem vertebrates, facilitating the evolution of larger, more-active modes of life2,3,5. However, this hypothesis lacks functional support in relevant taxa. Here we characterize the function of gills and skin in a vertebrate (lamprey ammocoete; Entosphenus tridentatus), a cephalochordate (amphioxus; Branchiostoma floridae) and a hemichordate (acorn worm; Saccoglossus kowalevskii) with the presumed burrowing, filter-feeding traits of vertebrate ancestors6-9. We provide functional support for a vertebrate origin of gas exchange at the gills with increasing body size and activity, as direct measurements in vivo reveal that gills are the dominant site of gas exchange only in ammocoetes, and only with increasing body size or challenges to oxygen supply and demand. Conversely, gills of all three taxa are implicated in ion regulation. Ammocoete gills are responsible for all ion flux at all body sizes, whereas molecular markers for ion regulation are higher in the gills than in the skin of amphioxus and acorn worms. This suggests that ion regulation at gills has an earlier origin than gas exchangethat is unrelated to vertebrate size and activity-perhaps at the very inception of pharyngeal pores in stem deuterostomes.

The emerging role of NOTCH3 receptor signalling in human lung diseases.

The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors (NOTCH1-4), with each receptor capable of regulating unique biological processes. Dysregulation of the NOTCH pathway has been associated with development and pathophysiology of multiple adult acute and chronic lung diseases. This includes accumulating evidence that alteration of NOTCH3 signalling plays an important role in the development and pathogenesis of chronic obstructive pulmonary disease, lung cancer, asthma, idiopathic pulmonary fibrosis and pulmonary arterial hypertension. Herein, we provide a comprehensive summary of the role of NOTCH3 signalling in regulating repair/regeneration of the adult lung, its association with development of lung disease and potential therapeutic strategies to target its signalling activity.

Mammalian enteral ventilation ameliorates respiratory failure

Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus). Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat. Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications. EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions. This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.

Effects on Ultrastructure, Composition and Specific Surface Area of the Gills of Odontesthes bonariensisUnder Subchronic Glyphosate-Based Herbicide Exposure.

Gills represent one of the major sites of gas exchange of fish, consequently they are in continuous close contact with the aquatic environment and its pollutants. In the present study the effects on gills of pejerrey fish, Odontesthes bonariensis, under glyphosate-based herbicide subchronic exposure were analyzed. Adult animals were exposed to sublethal concentrations of a glyphosate-based commercial formulation (1 and 10 PMG mg L-1, PMG: glyphosate active ingredient) for 15 days, while control group was maintained in rearing water. Ultrastructural changes in gills were observed by scanning electron microscopy (SEM). The composition of the surface epithelium and specific surface area were determined by energy dispersive spectroscopy (EDS) and N2 (g) adsorption-desorption isotherms, respectively. The herbicide exposure induced severe alterations in gill ultrastructure, as shown in the SEM micrographs. Accordingly, an increase in surface area of the gills of exposed animals was determined. These results support that gills parameters of freshwater fish are sensitive morphological biomarkers for glyphosate exposure.

The effect of age and training status on oxygen uptake kinetics in women

We examined the effect of age and training status on the oxygen uptake (V˙ O2) kinetics of untrained and recreationally trained women. Young (20–35yr), middle-age (40–55yr) and older (58–71yr) recreationally trained (YTR, n = 10; MTR, n = 12; OTR, n = 9) and untrained (YUT, n = 12; MUT, n = 10; OUT, n = 9) women participated in this crossectional study. Breath-by-breath V˙ O2 and near-infrared-spectroscopy-derived (NIRS) muscle deoxygenation [HHb] were monitored continuously during increasing and constant walking exercises. On-transition V˙ O2 and [HHb] responses to moderate intensity walking were modeled as mono-exponential. The data were normalized for each subject (0%–100 %), and [HHb]/ V˙ O2 ratio was calculated as the average [HHb]/ V˙ O2 during the 20- to 120-s period after the onset of moderate intensity walking exercise. The time constant of V˙ O2 (τ V˙ O2) was longer in OUT(23.8 ± 2.4), MUT(25.4 ± 5.1), YUT(23.1 ± 3.4) than in YTR(16.2 ± 2.0), MTR(16.7 ± 3.9), OTR(16.3 ± 2.8) women (p < 0.05). The [HHb]/ V˙ O2 ratio in OUT (1.31 ± 0.18) was higher than in YTR(1.08 ± 0.05), MTR(1.13 ± 0.09), YUT(1.12 ± 0.09) (p < 0.05). It is concluded that recreationally trained women had faster V˙ O2 kinetics along with better matching of O2 delivery and utilization at the site of gas exchange in the exercising muscles.

Bronchioalveolar stem cells: the crossroads of lung regeneration

Mammalian lungs are encased in dense endothelial cell networks to support systemic delivery of oxygen to vital organs (1-3), and to provide host pathogen defense by physical or chemical removal of foreign bodies (3,4). The evolutionary-refined architecture of mammalian lungs is primarily comprised of endoderm-derived epithelial cell populations (5); however, the lungs also harbour mesoderm-derived cells which contribute to the renin-angiotensin axis (6), innate immunity (3,4), and platelet production (7). Oronasal to parenchymal, the respiratory system is organized from the trachea, bronchi, bronchioles to the alveoli; the primary site of gas exchange (1,2).

Changes in pulmonary oxygen uptake and muscle deoxygenation kinetics during cycling exercise in older women performing walking training for 12 weeks.

This study examined the hypothesis that walking training (WT) could accelerate the slowed time constant (τ) of phase II in pulmonary oxygen uptake ([Formula: see text]O2) on-kinetics in older women. Also, we aimed to demonstrate that O2 delivery and O2 utilization were better matched at the site of gas exchange in exercising muscles when τ[Formula: see text]O2 was shortened. 20 recreationally active older women underwent WT sessions of approximately 60min, 3-4 times a week for 12 weeks. We assessed [Formula: see text]O2, heart rate (HR) and deoxygenated-hemoglobin concentration ([HHb]) kinetics during a constant-load exercise test before training (0 week-Pre), and at 6 and 12 weeks (6 weeks-Mid, 12 weeks-Post) throughout the training period. Maximal oxygen uptake ([Formula: see text]O2max) was unchanged throughout the training program. τHR tended to decline at Mid (58.6 ± 22.0s), and was significantly shorter at Post (51.7 ± 21.7s, p = 0.01) compared to Pre (67.1 ± 23.8s). τ[Formula: see text]O2 significantly decreased from 38.9 ± 8.6s for Pre, to 31.5 ± 7.9s for Mid (p = 0.02), and 32.3 ± 10.5s for Post (p = 0.03). The normalized [HHb] to [Formula: see text]O2 ratio (Δ[HHb]/Δ[Formula: see text]O2) at Pre (1.32 ± 0.93) gradually approached the perfectly matched value (= 1.0) at Mid (1.15 ± 0.61) and Post (1.07 ± 0.52). The restoration to baseline (≒ 30s) of the slower τ[Formula: see text]O2 due to WT, which may reflect better matching of O2 delivery and O2 utilization at the site of gas exchange, suggests that a longer period of WT could be a useful tool for improving exercise tolerance in older individuals.

Inflammatory responses in the initiation of lung repair and regeneration: their role in stimulating lung resident stem cells.

The lungs are the primary organs for respiration, the process by which carbon dioxide and oxygen are exchanged. The alveolus, which is the site of gas exchange in the lungs, consists of multiple cell types including alveolar epithelial cells, lung capillary endothelial cells and fibroblasts. Because of their complexity, lung parenchymal cells including epithelial lineage have been thought to have a lower rate of cellular turnover in adult lung. However, accumulating observations suggest that the turnover of parenchymal cells in adult lungs is essential for maintaining homeostasis during the steady state as well as for the repair and regeneration after lung injury. After lung injury by harmful pathogens, inflammation occurs to protect the host. Although excessive inflammation damages lung tissue, inflammatory cells are essential for regeneration because they remove harmful pathogens as well as debris derived from apoptotic and necrotic cells. In addition, subsets of inflammatory cells, especially phagocytic monocytes, produce cytokines and growth factors to resolve inflammation and promote tissue regeneration by stimulating tissue-resident stem cells. Recent advances in the biology of lung-resident stem cells, especially those addressing epithelial lineage, have revealed that there are several cellular populations capable of self-renewal that can differentiate into airway and/or alveolar epithelial cells. A part of these populations does not exist in the steady state but emerges after lung injury, suggesting that signals induced by inflammation may play an important role in initiating the proliferation and differentiation of lung stem or progenitor cells. Understanding the interaction between inflammatory responses and tissue-resident stem cells would help elucidate the pathogenesis of inflammatory lung diseases and promote the discovery of new therapeutic targets.

Effects of glyphosate and the glyphosate based herbicides Roundup Original® and Roundup Transorb® on respiratory morphophysiology of bullfrog tadpoles

Glyphosate-based herbicides are widely used in agriculture and are commonly found in water bodies. Roundup Original® (RO) contains an isopropylamine glyphosate (GLY) salt containing the surfactant POEA, while Roundup Transorb R® (RTR) contains a potassium salt of GLY with unknown surfactants. Both contain different compositions of so-called “inert” ingredients, more toxic than glyphosate. Amphibian tadpoles often experience variations in O2 availability in their aquatic habitats; an ability to tolerate hypoxia can condition their survival and fitness. We evaluated the impacts of sublethal concentrations of GLY (1 mg L−1), RO (1 mg L−1 GLY a.e) and RTR (1 mg L−1 GLY a.e) on metabolic rate (V·O2 – mLO2 Kg1 h−1) of bullfrog tadpoles during normoxia and graded hypoxia, and related this to morphology of their skin, their major site of gas exchange. In control (CT) V·O2 remained unaltered from normoxia until 40 mmHg, indicating a critical O2 tension between 40 and 20 mmHg. GLY significantly reduced V·O2, possibly due to epidermal hypertrophy, which increased O2 diffusion distance to O2 uptake. In contrast, RTR increased V·O2 during hypoxia, indicating an influence of “inert” compounds and surfactants. V·O2 of RO did not differ from CT, suggesting that any increase in V·O2 caused by exposure was antagonized by epidermal hypertrophy. Indeed, all herbicides caused marked alterations in skin morphology, with cell and epithelium wall presenting hyperplasia or hypertrophy and chromatid rupture. In summary, GLY, RO and RTR exert different effects in bullfrog tadpoles, in particular the surfactants and inert compounds appear to influence oxygen uptake.

Hagfish: Champions of CO2 tolerance question the origins of vertebrate gill function.

The gill is widely accepted to have played a key role in the adaptive radiation of early vertebrates by supplanting the skin as the dominant site of gas exchange. However, in the most basal extant craniates, the hagfishes, gills play only a minor role in gas exchange. In contrast, we found hagfish gills to be associated with a tremendous capacity for acid-base regulation. Indeed, Pacific hagfish exposed acutely to severe sustained hypercarbia tolerated among the most severe blood acidoses ever reported (1.2 pH unit reduction) and subsequently exhibited the greatest degree of acid-base compensation ever observed in an aquatic chordate. This was accomplished through an unprecedented increase in plasma [HCO3−] (>75 mM) in exchange for [Cl−]. We thus propose that the first physiological function of the ancestral gill was acid-base regulation, and that the gill was later co-opted for its central role in gas exchange in more derived aquatic vertebrates.

Intrapulmonary shunt and SCUBA diving: another risk factor?

Laboratory and field investigations have demonstrated that intrapulmonary arteriovenous anastomoses (IPAVA) may provide an additional means for venous gas emboli (VGE) to crossover to the arterial circulation due to their larger diameter compared to pulmonary microcirculation. Once thought to be the primary cause of decompression sickness (DCS), it has been demonstrated that, even in large quantities, their presence does not always result in injury. Normally, VGE are trapped in the site of gas exchange in the lungs and eliminated via diffusion. When VGE crossover takes place in arterial circulation, they have the potential to cause more harm as they are redistributed to the brain, spinal column, and other sensitive tissues. The patent foramen ovale (PFO) was once thought to be the only risk factor for an increase in arterialization; however, IPAVAs represent another pathway for this crossover to occur. The opening of IPAVAs is associated with exercise and hypoxic gas mixtures, both of which divers may encounter. The goal of this review is to describe how IPAVAs may impact diving physiology, specifically during decompression, and what this means for the individual diver as well as the future of commercial and recreational diving. Future research must continue on the relationship between IPAVAs and the environmental and physiological circumstances that lead to their opening and closing, as well as how they may contribute to diving injuries such as DCS.

Histopathological alteration in gill of channagachua exposed to an organophosphate

Channa gachua (family channidae) is an air breathing fish which live in oxygen depleted muddy water. The gill of fish is main site of gas exchange, ion regulation and nitrogen waste excretion .When fish exposed to sub-lethal concentration of Profenofos, an organophosphate pesticide, this pesticide enters into fish mainly through gills. The histopathological changes in the gills, due to exposure of Profenofos for 10 days, 15 days and 20 days include: curling and fusion in secondary lamellae, Hyperplasia, reduction in the respiratory surface area of filaments, fusion at the tip of the lamellae, sub- lamellar and sub epithelial space occur.

Using corrosion casts to understand oxygen delivery in the grasshopper leg

The light‐weight, air‐filled tracheal system has allowed insects to be the most evolutionary successful animals on the planet. Oxygen enters through spiracular openings before passing down tracheal tubes that branch into successively smaller tubes that eventually become tracheoles, which serve as the site of gas exchange. Depending on the species and life history stage, oxygen delivery down the tracheae may occur via diffusion, convection, or both. While adult Schistocerca americana grasshoppers use abdominal pumping and convection to drive oxygen through their head, thorax, and abdomen, it is less clear how oxygen delivery occurs down the metathoracic leg. We cannulated the tracheal system of an adult grasshopper and injected a low viscosity resin under vacuum, to create a corrosion cast of the major tracheal branches of the metathoracic leg. After the low viscosity resin had solidified, grasshopper tissue was digested leaving only the tracheal cast. Using light microscopy, we measured the radii of the main tracheae and their subsequent branches. These tracheal dimensions followed Murray's Law, suggesting that the network provided convective oxygen delivery. We will examine the casts using scanning electron microscopy to visualize tracheal branching patterns and estimate oxygen flow patterns throughout the metathoracic leg. This research has been supported by funding from Union College.

Roles for claudins in alveolar epithelial barrier function

Terminal airspaces of the lung, alveoli, are sites of gas exchange that are sensitive to disrupted fluid balance. The alveolar epithelium is a heterogeneous monolayer of cells interconnected by tight junctions at sites of cell-cell contact. Paracellular permeability depends on claudin (cldn)-family tight junction proteins. Of over a dozen alveolar cldns, cldn-3, cldn-4, and cldn-18 are the most highly expressed; other prominent alveolar claudins include cldn-5 and cldn-7. Cldn-3 is primarily expressed by type II alveolar epithelial cells, whereas cldn-4 and cldn-18 are expressed throughout the alveolar epithelium. Lung diseases associated with pulmonary edema, such as alcoholic lung syndrome and acute lung injury, affect alveolar claudin expression, which is frequently associated with impaired fluid clearance due to increased alveolar leak. However, recent studies have identified a role for increased cldn-4 in protecting alveolar barrier function following injury. Thus, alveolar claudins are dynamically regulated, tailoring lung barrier function to control the air-liquid interface.

Analysis of cutaneous and internal gill gas exchange morphology in early larval amphibians, Pseudophryne bibronii and Crinia georgiana

This study uses stereological techniques to examine body, internal gill and cardiovascular morphology of two larval amphibians, Pseudophryne bibronii and Crinia georgiana, to evaluate the roles of diffusive and convective gas exchange. Gosner stage 27 specimens were prepared for light microscopy and six parallel sections of equal distance taken through the body as well as a further six through the heart and internal gills. Body, internal gill and heart volume as well as body and internal gill surface areas were determined. The harmonic mean distance across the internal gills was also measured and used to estimate oxygen diffusive conductance, DO₂. The species were of similar body size and surface area, but the heart and internal gills were larger in P. bibronii, which may represent precursors for greater growth of the species beyond stage 27. The much larger surface area of the skin compared to the internal gills in both species suggests it is the main site for gas exchange, with the gills supplementing oxygen uptake. The sparse cutaneous capillary network suggests diffusion is the main oxygen transport mechanism across the skin and directly into deeper tissues. A numerical model that simplifies larval shape, and has an internal (axial vessels) and external oxygen source, confirms that diffusion is able to maintain tissue oxygen with limited convective input.

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

BackgroundDistal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored.MethodIn a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation.ResultsHere, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA.ConclusionOur findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia.

Cutaneous vasoregulation during short- and long-term aerial acclimation in the amphibious mangrove rivulus, Kryptolebias marmoratus

The mangrove rivulus (Kryptolebias marmoratus) is an amphibious fish and evidence suggests that the cutaneous surface is the primary site of gas exchange during emersion. The aim of this study was to determine whether cutaneous blood vessels were regulated in the caudal fin during the initial transition from water to aerial exposure, and after 10 days of aerial acclimation. Acute changes (first 3 min following emersion) in the cutaneous vessels diameter were measured in real-time on live fish using light microscopy. The data show that under control conditions, only arterioles in the caudal fin were vasoactive. During the first 20s of aerial acclimation the arterioles significantly constricted (-2.1 ± 0.4 μm), which was followed immediately by a relaxation (from 40 to 180 s). This vasoconstriction was eliminated with the addition of phentolamine (50 μmoll(-1)), which indicates that the vasoconstriction was mediated by α-adrenoreceptors. Longer-term changes in the cutaneous surface vasculature were determined using fluorescent immunohistochemistry and antibodies for the endothelial marker, CD31. Fish aerially acclimated for 10 days exhibited significantly higher levels of endothelial fluorescence in the caudal fin when compared to control fish in water, indicating endothelial cell production (i.e. angiogenesis). These data combined show that for every emersion episode, there is an initial α-adrenergic mediated vasoconstriction, which is most likely, a stress response. This is then followed by a long-term acclimation involving an upregulation in endothelial cell production, which would subsequently enhance blood perfusion to the cutaneous surface and potentially increase the capacity for gas exchange with the external environment.