Application of respiratory heat exchange for the measurement of lung water.

A noninvasive method for measuring pulmonary blood flow and lung mass (called airway thermal volume), based on the measurements of lung heat exchange with environment, is described. The lungs function as a steady-state heat exchange system, having an inner heat source (pulmonary blood flow) and an external heat sink (ventilation). Sudden changes in the steady-state condition, such as caused by hyperventilation of dry air, lead to a new steady state after a few minutes. The expired air temperature difference between the initial and final steady states is proportional to pulmonary blood flow, whereas the rate at which the new steady state is achieved is proportional to airway thermal volume. The method was tested in 20 isolated dogs lungs, 9 perfused goat lungs, and 27 anesthetized sheep. The expired air temperature fall during hyperventilation was inversely proportional to the perfusion rate of the isolated lungs, and half-time of the temperature fall was proportional to the lung tissue mass. Experiments in anesthetized sheep showed that the measured airway thermal volume is close to the total mass of the excised lungs, including its residual blood (r = 0.98). Pulmonary edema and fluid instillation into the bronchial tree increased in the measured lung mass.     

Oxygen consumption in the lungs of dogs with external hemorrhage and after reinfusion of blood

In experiments on 10 dogs with external blood loss and reinfusion it was demonstrated, that in hemorrhagic and posthemorrhagic periods oxygen consumption by the organism is determined not only by O2 demands of the large circulation tissues, but to a great extent by demands in O2 in the system of lesser circulation, what is being evidenced by activation of the metabolic function of the lungs. It turned out that in pathogenesis of postinfusion respiratory insufficiency reactions of lipid oxidation in the lungs play a significant role.     

Coupled evolution of digestive,respiratory, circulatory,and excretory systems: A model investigation

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems as the single system. The model is realized on the basis of the language STEL-LA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.     

Coupled evolution of digestive, respiratory, circulatory, and excretory systems: a model investigation

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems at the single system. The model is realized on the basis of the language STELLA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases of the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.     

从肺肠关系探讨肠道菌群与儿童哮喘的关系

儿童哮喘是一种肺部疾病,肠道菌群在其免疫和代谢等诸多方面扮演着重要角色,肺肠之间微妙的关系可能是影响疾病发生、发展及预后的潜在机制。通过分析肺与肠的结构和功能,发现从中医学和现代医学角度均可证实肺肠具有表里同源关系。津液/黏液是肺肠之间的重要物质,影响哮喘儿童痰的生成及变化。肺肠之间的微生物可随津液/黏液定植,且菌群结构的变化又与儿童哮喘密切相关。基于肺肠结构关系及二者间物质的沟通作用,发现哮喘患儿不仅存在肠道菌群失衡,且肠道菌群与免疫应答和肠道代谢之间的关系,可能是防治儿童哮喘的新途径,值得进一步探索。

     

Demonstration of prostaglandin activity in lungs of the rainbow lizard (Agama agama) by bioassay

Extracts and perfusate effluents of lungs of the rainbow lizard (Agama agama) were assayed for prostaglandin-like activity. Results of differential bioassay and thin-layer chromatography suggested that the prostanoid was predominantly PGE2-like. The mean PGE2-like content of 10 lizard lung extracts was 2.9 micrograms g-1 wet weight compared with 146 ng g-1 in rat lungs. Mechanical pressure applied to the lung during perfusion through the pulmonary vasculature provoked the release of large quantities of PGE2-like material. This release was blocked by fatty acid cyclooxygenase inhibitors. Compared with guinea-pig and rat lungs, lizard lungs exhibited a markedly low capacity for inactivating PGE2. In view of an apparently high prostaglandin-forming and a low inactivating capacity, we speculate that under certain circumstances, lizard lungs may release vasoactive substances into the circulation.     

Pulmonary complications of smoked substance abuse.

After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cells in the lungs'' immune defense system. In addition, the available evidence strongly suggests that regularly smoking marijuana may predispose to the development of cancer of the respiratory tract. "Crack" smoking has become increasingly prevalent in our society, especially among habitual smokers of marijuana. New evidence is emerging implicating smoked cocaine as a cause of acute respiratory tract symptoms, lung dysfunction, and, in some cases, serious, life-threatening acute lung injury. A strong physician message to users of marijuana, cocaine, or both concerning the harmful effects of these smoked substances on the lungs and other organs may persuade some of them, especially those with drug-related respiratory complications, to quit smoking.     

A comparison of the antigenic characteristics of rat and human Pneumocystis carinii by immunoblotting

The antigenic characteristics of rat Pneumocystis carinii obtained from infected lungs and grown in tissue culture were compared with the properties of human P. carinii obtained from the lungs of AIDS and non-AIDS patients by the immunoblotting technique, using different sources of antibody. Major immunoreactive bands of 45, 50, and 116 kd were found in both lung and tissue culture-derived rat P. carinii, suggesting the organism retains its antigenic characteristics in short-term culture. The principal immunoreactive bands in human P. carinii included a band of 40 kd, and to a lesser extent, a band of 66 kd; these antigens were found in the lungs of six and seven AIDS patients but in only one of eight non-AIDS patients with pneumocystosis. The rat and human P. carinii antigens reacted with sera from immunized rabbits, from rats with pneumocystosis and prolonged environmental exposure to the organism, from AIDS and non-AIDS P. carinii patients, and from healthy blood donors. Reactivity of these antigens could be removed by adsorption of antisera with P. carinii-infected lungs but not with normal lungs or lungs infected with bacteria and fungi. We conclude that rat and human P. carinii have shared, as well as species-specific, antigenic determinants, which should be useful for a variety of studies with this organism.     

Function of alveoli as a result of evolutionary development of respiratory system in mammals

Reaction of hemoglobin oxygenation is known to occur for 40 femtoseconds (40 × 10^?15 s). However, the process of oxygen diffusion to hemoglobin under physiologic conditions decelerated this reaction approximately billion times. In mammalian lungs, blood is moving at a high rate and in a relatively high amount. The human lung mass is as low as 600 g, but the complete cardiac output approaches 6 l/min. In rat, from 20 to 40 ml of blood is passed for one minute through the lung whose mass is about 1.5 g. Such blood flow rate is possible, as in lungs of high animals there exists a dense network of relatively large microvessels with diameter from 20 to 40 μm and more. In spite of a large volume and a high blood flow rate hampering oxygen diffusion, the complete blood oxygenation occurs in lung alveoli. This is due to peculiar mechanisms that facilitate markedly the oxygen diffusion and that developed in alveoli of mammals in the course of many million years of evolution of their respiratory system. Thus, alveolus is not a bubble with air, but a complex tool of fight with inertness of diffusion. It is interesting that in lungs of the low vertebrates, neither such system of blood vessels nor alveoli exist, and their blood flow rate is much lower than in mammals.     

Structural aspects of gas exchange

The lung is composed of several million small air spaces, lined by a delicate tissue membrane separating air from capillary blood. The design features of the gas exchange region in the lung are optimal for gaseous diffusion, by having a very extensive contact surface but with a minimal tissue barrier composed of an epithelial and endothelial layer separating an interstitial layer. The extent of the gas exchange surface in adult lungs is determined by general maturation which in turn is influenced by metabolic requirements of the organism. Environmental factors can modulate the pattern of ultimate lung development. Lung inflation causes air spaces to expand mainly by a process of tissue unfolding beneath an extremely thin layer of alveolar surfactant. This ensures cellular integrity during extreme deformations while at the same time providing a reserve of gas exchange surface so that functional diffusion capacity at all lung volumes is less than the structural maximum.     

Determination of the inequality of ventilation by the helium mixing time in a spirograph--lung system

The dependence of the time of He mixing in the lung-spyrograph system upon the factors influencing its value was taken into consideration. Cases of equal lung ventilation of the lungs were graphically illustrated; the "ideal" mixing time was determined with the aid of these diagrams. It is suggested that the inequality of the lung ventilation can be judged by the value by which the mixing time obtained in the examination of the patient's respiration exceeded the "ideal" one found by the diagram in the same patient.     

一种猪模型的体外肺灌注系统的建立

目的:体外肺灌注技术(Ex vivo lung perfusion, EVLP)对于肺移植的实施意义重大,但成本昂贵。本文采用国产经济材料建立猪模型的EVLP系统,以探索保证系统性能的同时降低移植费用。方法:我们首先依据国产材料配置肺灌注液,并组装管道、连接仪器以建立EVLP系统;之后通过外科手段获得3头家猪的肺脏,并灌注肺灌注液,低温保存6小时;最后我们将肺脏连接到EVLP系统,通过血气分析和肺功能检查来评估肺脏随时间变化的状况。结果:离体并在低温保存6小时的猪肺脏,通过我们建立的相对经济的EVLP系统,可以在2小时内维持良好的氧合功能和肺生理指标:肺动脉压、气道峰压、平台压力、肺动脉氧气分压和二氧化碳分压和左心房的氧气分压和二氧化碳分压都保持稳定,同时肺脏具有正常的颜色和弹性,没有明显水肿和功能损害。结论:我们建立的EVLP系统可以有效地维护离体猪肺的生理功能,且降低了成本,从而为肺移植体外肺灌注技术的优化应用提供了研究基础。     

A gross and microscopic study of the respiratory anatomy of the Antarctic Weddell seal, Leptonychotes weddelli.

Four species of Phocidae, or true seals, inhabit the waters surrounding the Antarctic continent. These animals are thought to have different diving capabilities. The Weddell seal, Leptonychotes weddelli, is known to be capable of attaining depths up to 600 meters. The respiratiory system of the Weddell seal shows the usual adaptations to an aquatic environment characteristic of other marine. These include lungs that undergo compression acollapse at depths greater than 70 meters; hyaline cartilage in the tracheo-bronchial tree as far as the terminal bronchioles; and large amounts of smooth muscle surrounding the distal-most bronchioles. The collapsible lungs provide a mechanism by which air is forced from the alveoli adjacent to the pulmonary capillary beds thereby preventing the absorption of nitrogen gas into the bloodsteam. The presence of hyaline cartilage throughout most of the tracheo-bronchial tree increases the effective dead air space that accommodates most of the air forced from the collapsed lungs. The smooth muscle surrounding the respiratory bronchioles prevents their collapse while under the pressures of a deep dive. Collapse of the respiratory bronchioles not supported by cartilage would trap air in the lung alveoli during a dive. In addition, large- sac-like "diverticulae" are found in the submucosa throughout the tracheo-bronchial tree. These diverticulae, which open directly into the lumen of the tree, appear to be modified glands whose cells, in most cases, do not appear to be specialized for secretory function. They are most numerous in the more distal bronchi and terminal bronchioles where they are situated on both the luminal and adventitial sides of the hyaline cartilage supporting the walls of the air passages. Diverticulae are not found in the respiratory bronchioles or in the respiratory portion of the lungs.     

High blood pressure,antihypertensive medication and lung function in a general adult population

Background

Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population.

Methods

Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function.

Results

High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R²: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R²: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R²: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R²: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too.

Conclusion

Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult population.     

Effect of proteolytic enzymes on transepithelial solute transport

The effects of proteases on air-space clearance (AC) of small ([14C]sucrose, 342 daltons) and large (125I-neutral dextran, 70,000 daltons) solutes were studied in isolated, fluid-filled hamster lungs that were perfused in a nonrecirculating system. When instilled into the air spaces, porcine pancreatic elastase (0.1-0.4 mg/ml) and bovine pancreatic trypsin (BPT) (0.5-2.0 mg/ml), but neither Clostridium histolyticum collagenase (5.0 mg/ml) nor phenylmethylsulfonyl fluoride-inactivated BPT caused large increases in the AC of both tracer molecules. BPT-induced solute clearance was further characterized functionally and morphologically. The functional characteristics of solute AC under steady-state conditions did not indicate that transepithelial transport was diffusion-limited. Inhibition by millimolar concentrations of Zn2+ and by lung cooling, along with electron microscopic studies employing horseradish peroxidase as a macromolecule tracer, were consistent with epithelial solute transport by a vesicular mechanism (transcytosis). Solute transport from the interstitial compartment to the lung exterior was shown to occur via two pathways. By unknown mechanisms BPT caused small amounts of water to flow through an incompletely identified, extravascular pathway. In BPT-exposed lungs efflux of 125I-dextran 70 occurred almost exclusively through this pathway, whereas [14C]sucrose was transported to the lung exterior partly through this same pathway and partly through the vasculature. The large differences in the diffusion coefficients of the two tracers may have accounted for these observed patterns of solute efflux from the lung. The possible significance of our findings to the pathogenesis of experimental emphysema are discussed.     

Lack of change in the composition of fetal lamb lung surfactant during gestation

Fetal surfactant from lamb lung fluids collected daily from day 114 to day 146 of gestation, was isolated by centrifugation (pellet material) and further purified by sucrose density gradient centrifugation. The concentration of the pellet material from lung fluid (crude surfactant) increased from day 125 till day 135 and fluctuated strongly from that period onwards, whereas lung fluid secretion increased linearly until a few days before parturition. The pellet phospholipid composition changed with gestational age, suggesting biochemical maturation of the surfactant-producing system. The purified surfactant fraction, of which approximately 85% was phosphatidylcholine, did not change however from day 122 onwards except for a small increase in the percentage of phosphatidylglycerol. Alveolar wash surfactant or the lamellar body material, isolated from fetal lungs at different gestational ages had the same composition as surfactant from lung fluids. Only the composition of lamellar bodies of '125 day' lungs differed slightly from that of the lung fluid surfactant. The similar characteristics of all purified surfactant fractions throughout gestation indicate that, in the fetal lamb, lung maturation is associated with an increase in surfactant production no significant changes in phospholipid composition.     

Pulmonary clearance of inhaled 99mTc-DTPA: effects of surfactant depletion by lung lavage

The influence of surfactant depletion on clearance from the lungs of inhaled technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was studied in rabbits. Surfactant was removed by repeated lung lavage with isotone saline. To minimize structural damage to the lungs, pressure generated insufflation with short expiration was utilized. Aerosolized 99mTc-DTPA was administered via a bag-in-bottle system. Radioactivity was measured with a gamma camera and time-activity curves were obtained over the base of the right lung. Six nonlavaged rabbits served as controls. In six lavaged rabbits clearance of 99mTc-DTPA was significantly faster than in controls. In three rabbits given natural surfactant into the trachea after lung lavage, 99mTc-DTPA was eliminated faster than in controls but slower than in surfactant-depleted animals. The results indicate a role of surfactant on clearance rate of 99mTc-DTPA from rabbit lungs. Measurements of 99mTc-DTPA clearance may be useful in studying the function of the surfactant system in different lung disorders.     

Utilization of data obtained in pilot acute experiments for practical hygienic assessment of a chemical substance

A large number of the chemical substances and preparations (compositions) that are incorporated into the national economy cannot be subjected to long-term and detailed testing for toxicity and safety. There are simple methods on the acute experimental level which can serve as a basis for working out the necessary prophylactic measures in introducing new substances into the industry. Determination of LD50 upon intragastric administration, intravenous administration (model of rapid penetration into the organism), static inhalatory treatment under saturated concentration, determination of the primary local effect of the skin and mucous membranes, together with careful observation of the behaviour of the experimental animals, signs of their intoxication and their death, as well as comparison of the physico-chemical properties of the substance and its already familiar structural analogues may serve as the ground for predicting the biological significance of the new substance even at longer terms of contact with the organism and making toxicological and hygienic assessments under concrete technological conditions.     

肠道菌群在机体免疫调节功能中的作用

肠道菌群被称为是人体的一个重要"器官",具有数量庞大、种类繁多等特点,对人体具有重要的生理与病理意义。肠道菌群对机体免疫功能的影响日益受到广泛关注。本文主要就肠道菌群对肠道形态及功能、肠道黏膜免疫系统以及肠道外免疫系统三个方面的影响进行综述。     

Pulmonary and gastric surfactants. A comparison of the effect of surface requirements on function and phospholipid composition

Surfactant is present in the alveoli and conductive airways of mammalian lungs. The presence of surface active agents was, moreover, demonstrated for avian tubular lungs and for the stomach and intestine. As the surface characteristics of these organs differ from each other, their surfactants possess distinct biochemical and functional characteristics. In the stomach so-called 'gastric surfactant' forms a hydrophobic barrier to protect the mucosa against acid back-diffusion. For this purpose gastric mucosal cells secrete unsaturated phosphatidylcholines (PC), but no dipalmitoyl-PC (PC16:0/16:0). By contrast, surfactant from conductive airways, lung alveoli and tubular avian lungs contain PC16:0/16:0 as their main component in similar concentrations. Hence, there is no biochemical relation between gastric and pulmonary surfactant. Alveolar surfactant, being designed for preventing alveolar collapse under the highly dynamic conditions of an oscillating alveolus, easily reaches values of <5 mN/m upon cyclic compression. Surfactants from tubular air-exposed structures, however, like the conductive airways of mammalian lungs and the exclusively tubular avian lung, display inferior compressibility as they only reach minimal surface tension values of approximately 20 mN/m. Hence, the highly dynamic properties of alveolar surfactant do not apply for surfactants designed for air-liquid interfaces of tubular lung structures.