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1
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Lew VL. The circulatory dynamics of human red blood cell homeostasis: Oxy-deoxy and PIEZO1-triggered changes. Biophys J 2023; 122:484-495. [PMID: 36588342 PMCID: PMC9941722 DOI: 10.1016/j.bpj.2022.12.038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/14/2022] [Accepted: 12/30/2022] [Indexed: 01/02/2023] Open
Abstract
The vital function of red blood cells (RBCs) is to mediate the transport of oxygen from lungs to tissues and of CO2 from tissues to lungs. The gas exchanges occur during capillary transits within fractions of a second. Each oxygenation-deoxygenation and deoxygenation-reoxygenation transition on hemoglobin triggers sharp changes in RBC pH, leading to downstream changes in ion fluxes, membrane potential, and cell volume. The dynamics of these changes during the variable periods between capillary transits in vivo remains a mystery inaccessible to study by current methodologies, a knowledge gap on a fundamental physiological process that is the focus of the present study. The use of a computational model of human RBC homeostasis of tested accreditation enabled a detailed investigation of the expected RBC changes during intercapillary transits, with results advancing novel insights and predictions. The predicted rates of relative RBC volume change on oxygenation-deoxygenation (oxy-deoxy) and deoxygenation-reoxygenation transitions were about 1.5%/min and -0.9%/min, respectively, far too slow to allow the cells to reach steady states in the intervals between capillary transits. The amplitude of the oxy-deoxy-reoxygenation volume fluctuations varied in proportion with the duration of the intercapillary transit intervals. Upon capillary entry, oxy-deoxy-induced changes occur concurrently with deformation-induced PIEZO1 channel activation, both processes affecting cell pH, membrane potential, and cell volume during intertransit periods. The model showed that the effects were strictly additive as expected from processes operating independently on the cell's homeostatic fabric. Analysis of the mechanisms behind these predictions revealed, for the first time, the complex interactions between oxy-deoxy and ion transport processes that ensure the long-term homeostatic stability of RBCs for optimal gas transport in physiological conditions and how these may become altered in diseased states. Possible designs of microfluidic devices to test the model predictions are discussed.
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Affiliation(s)
- Virgilio L Lew
- Physiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, United Kingdom.
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Ferretti G, Fagoni N, Taboni A, Vinetti G, di Prampero PE. A century of exercise physiology: key concepts on coupling respiratory oxygen flow to muscle energy demand during exercise. Eur J Appl Physiol 2022; 122:1317-1365. [PMID: 35217911 PMCID: PMC9132876 DOI: 10.1007/s00421-022-04901-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 01/25/2022] [Indexed: 12/26/2022]
Abstract
After a short historical account, and a discussion of Hill and Meyerhof's theory of the energetics of muscular exercise, we analyse steady-state rest and exercise as the condition wherein coupling of respiration to metabolism is most perfect. The quantitative relationships show that the homeostatic equilibrium, centred around arterial pH of 7.4 and arterial carbon dioxide partial pressure of 40 mmHg, is attained when the ratio of alveolar ventilation to carbon dioxide flow ([Formula: see text]) is - 21.6. Several combinations, exploited during exercise, of pertinent respiratory variables are compatible with this equilibrium, allowing adjustment of oxygen flow to oxygen demand without its alteration. During exercise transients, the balance is broken, but the coupling of respiration to metabolism is preserved when, as during moderate exercise, the respiratory system responds faster than the metabolic pathways. At higher exercise intensities, early blood lactate accumulation suggests that the coupling of respiration to metabolism is transiently broken, to be re-established when, at steady state, blood lactate stabilizes at higher levels than resting. In the severe exercise domain, coupling cannot be re-established, so that anaerobic lactic metabolism also contributes to sustain energy demand, lactate concentration goes up and arterial pH falls continuously. The [Formula: see text] decreases below - 21.6, because of ensuing hyperventilation, while lactate keeps being accumulated, so that exercise is rapidly interrupted. The most extreme rupture of the homeostatic equilibrium occurs during breath-holding, because oxygen flow from ambient air to mitochondria is interrupted. No coupling at all is possible between respiration and metabolism in this case.
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Affiliation(s)
- Guido Ferretti
- Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Brescia, Italy.
- Département d'Anesthésiologie, Pharmacologie et Soins Intensifs, Université de Genève, Genève, Switzerland.
| | - Nazzareno Fagoni
- Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Brescia, Italy
| | - Anna Taboni
- Département d'Anesthésiologie, Pharmacologie et Soins Intensifs, Université de Genève, Genève, Switzerland
| | - Giovanni Vinetti
- Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Brescia, Italy
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Hamedani H, Kadlecek S, Ruppert K, Xin Y, Duncan I, Rizi RR. Ventilation heterogeneity imaged by multibreath wash-ins of hyperpolarized 3 He and 129 Xe in healthy rabbits. J Physiol 2021; 599:4197-4223. [PMID: 34256417 DOI: 10.1113/jp281584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 06/30/2021] [Indexed: 12/20/2022] Open
Abstract
KEY POINTS Multibreath imaging to estimate regional gas mixing efficiency is superior to intensity-based single-breath ventilation markers, as it is capable of revealing minute but essential measures of ventilation heterogeneity which may be sensitive to subclinical alterations in the early stages of both obstructive and restrictive respiratory disorders. Large-scale convective stratification of ventilation in central-to-peripheral directions is the dominant feature of observed ventilation heterogeneity when imaging a heavy/less diffusive xenon gas mixture; smaller-scale patchiness, probably originating from asymmetric lung function at bronchial airway branching due to the interaction of convective and diffusive flows, is the dominant feature when imaging a lighter/more diffusive helium gas mixture. Since detecting low regional ventilation is crucial for characterizing diseased lungs, our results suggest that dilution with natural abundance helium and imaging at higher lung volumes seem advisable when imaging with hyperpolarized 129 Xe; this will allow the imaging gas to reach slow-filling and/or non-dependent lung regions, which might otherwise be impossible to distinguish from total ventilation shunt regions. The ability to differentiate these regions from those of total shunt is worse with typical single-breath imaging techniques. ABSTRACT The mixing of freshly inhaled gas with gas already present in the lung can be directly assessed with heretofore unachievable precision via magnetic resonance imaging of signal build-up resulting from multiple wash-ins of a hyperpolarized (HP) gas. Here, we used normoxic HP 3 He and 129 Xe mixtures to study regional ventilation at different spatial scales in five healthy mechanically ventilated supine rabbits at two different inspired volumes. To decouple the respective effects of density and diffusion rates on ventilation heterogeneity, two additional studies were performed: one in which 3 He was diluted with an equal fraction of natural abundance xenon, and one in which 129 Xe was diluted with an equal fraction of 4 He. We observed systematic differences in the spatial scale of specific ventilation heterogeneity between HP 3 He and 129 Xe. We found that large-scale, central-to-peripheral convective ventilation inhomogeneity is the dominant cause of observed heterogeneity when breathing a normoxic xenon gas mixture. In contrast, small-scale ventilation heterogeneity in the form of patchiness, probably originating from asymmetric lung function at bronchial airway branching due to interactions between convective and diffusive flows, is the dominant feature when breathing a normoxic helium gas mixture, for which the critical zone occurs more proximally and at an imageable spatial scale. We also showed that the existence of particular underventilated non-dependent lung regions when breathing a heavy gas mixture is the result of the density of that mixture - rather than, for example, its diffusion rate or viscosity. Finally, we showed that gravity-dependent ventilation heterogeneity becomes substantially more uniform at higher inspired volumes for xenon gas mixtures compared to helium mixtures.
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Affiliation(s)
- Hooman Hamedani
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Penn Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Stephen Kadlecek
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kai Ruppert
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yi Xin
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Penn Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ian Duncan
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Rahim R Rizi
- Department of Radiology, Functional and Metabolic Imaging Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Ortiz-Prado E, Dunn JF, Vasconez J, Castillo D, Viscor G. Partial pressure of oxygen in the human body: a general review. AMERICAN JOURNAL OF BLOOD RESEARCH 2019; 9:1-14. [PMID: 30899601 PMCID: PMC6420699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 12/23/2018] [Indexed: 06/09/2023]
Abstract
The human body is a highly aerobic organism, in which it is necessary to match oxygen supply at tissue levels to the metabolic demands. Along metazoan evolution, an exquisite control developed because although oxygen is required as the final acceptor of electron respiratory chain, an excessive level could be potentially harmful. Understanding the role of the main factors affecting oxygen availability, such as the gradient of pressure of oxygen during normal conditions, and during hypoxia is an important point. Several factors such as anaesthesia, hypoxia, and stress affect the regulation of the atmospheric, alveolar, arterial, capillary and tissue partial pressure of oxygen (PO2). Our objective is to offer to the reader a summarized and practical appraisal of the mechanisms related to the oxygen's supply within the human body, including a facilitated description of the gradient of pressure from the atmosphere to the cells. This review also included the most relevant measuring methods of PO2 as well as a practical overview of its reference values in several tissues.
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Affiliation(s)
- Esteban Ortiz-Prado
- OneHealth Research Group, Universidad De Las AmericasQuito, Ecuador
- Physiology Section, Department of Cell Biology, Physiology and Immunology, Universitat de BarcelonaBarcelona, Spain
| | - Jeff F Dunn
- Cumming School of Medicine, University of CalgaryCalgary, Canada
| | - Jorge Vasconez
- OneHealth Research Group, Universidad De Las AmericasQuito, Ecuador
| | - Diana Castillo
- OneHealth Research Group, Universidad De Las AmericasQuito, Ecuador
| | - Ginés Viscor
- Physiology Section, Department of Cell Biology, Physiology and Immunology, Universitat de BarcelonaBarcelona, Spain
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Bossé Y. The Strain on Airway Smooth Muscle During a Deep Inspiration to Total Lung Capacity. JOURNAL OF ENGINEERING AND SCIENCE IN MEDICAL DIAGNOSTICS AND THERAPY 2019; 2:0108021-1080221. [PMID: 32328568 PMCID: PMC7164505 DOI: 10.1115/1.4042309] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/06/2018] [Indexed: 02/05/2023]
Abstract
The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a growing body of in vitro studies investigating the effect of stretching ASM by different magnitudes on its contractility. The relevance of these in vitro findings remains uncertain, as the real range of strains ASM undergoes in vivo during a DI is somewhat elusive. In order to understand the regulation of ASM contractility by a DI and to infer on its putative contribution to the bronchodilator effect of a DI, it is imperative that in vitro studies incorporate levels of strains that are physiologically relevant. This review summarizes the methods that may be used in vivo in humans to estimate the strain experienced by ASM during a DI from functional residual capacity (FRC) to total lung capacity (TLC). The strengths and limitations of each method, as well as the potential confounders, are also discussed. A rough estimated range of ASM strains is provided for the purpose of guiding future in vitro studies that aim at quantifying the regulatory effect of DI on ASM contractility. However, it is emphasized that, owing to the many limitations and confounders, more studies will be needed to reach conclusive statements.
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Affiliation(s)
- Ynuk Bossé
- Université Laval, Faculty of Medicine, Department of Medicine, IUCPQ, M2694, Pavillon Mallet, Chemin Sainte-Foy, Québec, QC G1V 4G5, Canada e-mail:
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Yamaguchi K, Tsuji T, Aoshiba K, Nakamura H, Abe S. Anatomical backgrounds on gas exchange parameters in the lung. World J Respirol 2019; 9:8-29. [DOI: 10.5320/wjr.v9.i2.8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 11/11/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023] Open
Abstract
Many problems regarding structure-function relationships have remained unsolved in the field of respiratory physiology. In the present review, we highlighted these uncertain issues from a variety of anatomical and physiological viewpoints. Model A of Weibel in which dichotomously branching airways are incorporated should be used for analyzing gas mixing in conducting and acinar airways. Acinus of Loeschcke is taken as an anatomical gas-exchange unit. Although it is difficult to define functional gas-exchange unit in a way entirely consistent with anatomical structures, acinus of Aschoff may serve as a functional gas-exchange unit in a first approximation. Based on anatomical and physiological perspectives, the multiple inert-gas elimination technique is thought to be highly effective for predicting ventilation-perfusion heterogeneity between acini of Aschoff under steady-state condition. Changes in effective alveolar PO2, the most important parameter in classical gas-exchange theory, are coherent with those in mixed alveolar PO2 decided from the multiple inert-gas elimination technique. Therefore, effective alveolar-arterial PO2 difference is considered useful for assessing gas-exchange abnormalities in lung periphery. However, one should be aware that although alveolar-arterial PO2 difference sensitively detects moderately low ventilation-perfusion regions causing hypoxemia, it is insensitive to abnormal gas exchange evoked by very low and high ventilation-perfusion regions. Pulmonary diffusing capacity for CO (DLCO) and the value corrected for alveolar volume (VAV), i.e., DLCO/VAV (KCO), are thought to be crucial for diagnosing alveolar-wall damages. DLCO-related parameters have higher sensitivity to detecting abnormalities in pulmonary microcirculation than those in the alveolocapillary membrane. We would like to recommend four categories derived from combining behaviors of DLCO with those of KCO for differential diagnosis on anatomically morbid states in alveolar walls: type-1 abnormality defined by decrease in both DLCO and KCO; type-2 abnormality by decrease in DLCO but increase in KCO; type-3 abnormality by decrease in DLCO but restricted rise in KCO; and type-4 abnormality by increase in both DLCO and KCO.
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Affiliation(s)
- Kazuhiro Yamaguchi
- Department of Respiratory Medicine, Tokyo Medical University, Tokyo 160-0023, Japan
| | - Takao Tsuji
- Department of Respiratory Medicine, Tokyo Medical University, Tokyo 160-0023, Japan
| | - Kazutetsu Aoshiba
- Department of Respiratory Medicine, Tokyo Medical University, Ibaraki Medical Center, Ibaraki 300-0395, Japan
| | - Hiroyuki Nakamura
- Department of Respiratory Medicine, Tokyo Medical University, Ibaraki Medical Center, Ibaraki 300-0395, Japan
| | - Shinji Abe
- Department of Respiratory Medicine, Tokyo Medical University, Tokyo 160-0023, Japan
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Arai TJ, Horn FC, Sá RC, Rao MR, Collier GJ, Theilmann RJ, Prisk GK, Wild JM. Comparison of quantitative multiple-breath specific ventilation imaging using colocalized 2D oxygen-enhanced MRI and hyperpolarized 3He MRI. J Appl Physiol (1985) 2018; 125:1526-1535. [PMID: 30161004 PMCID: PMC6295484 DOI: 10.1152/japplphysiol.00500.2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 08/08/2018] [Accepted: 08/20/2018] [Indexed: 11/22/2022] Open
Abstract
Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-1H) and hyperpolarized 3He (HP-3He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for 1H configured with the 3He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3 × 3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-1H: 0.28 (0.08) and HP-3He: 0.32 (0.14)], SVwidths [OE-1H: 0.28 (0.08) and HP-3He: 0.27 (0.10)], and SVslopes [OE-1H: -0.016 (0.006) cm-1 and HP-3He: -0.013 (0.007) cm-1]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized 3He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.
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Affiliation(s)
- Tatsuya J Arai
- POLARIS, Academic Unit of Radiology, University of Sheffield , Sheffield , United Kingdom
- Pulmonary Imaging Laboratory, University of California, San Diego, La Jolla, California
| | - Felix C Horn
- POLARIS, Academic Unit of Radiology, University of Sheffield , Sheffield , United Kingdom
| | - Rui Carlos Sá
- Pulmonary Imaging Laboratory, University of California, San Diego, La Jolla, California
| | - Madhwesha R Rao
- POLARIS, Academic Unit of Radiology, University of Sheffield , Sheffield , United Kingdom
| | - Guilhem J Collier
- POLARIS, Academic Unit of Radiology, University of Sheffield , Sheffield , United Kingdom
| | - Rebecca J Theilmann
- Pulmonary Imaging Laboratory, University of California, San Diego, La Jolla, California
| | - G Kim Prisk
- Pulmonary Imaging Laboratory, University of California, San Diego, La Jolla, California
| | - Jim M Wild
- POLARIS, Academic Unit of Radiology, University of Sheffield , Sheffield , United Kingdom
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8
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Updating a gas dynamics model using estimates for California sea lions (Zalophus californianus). Respir Physiol Neurobiol 2016; 234:1-8. [PMID: 27562522 DOI: 10.1016/j.resp.2016.08.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 07/24/2016] [Accepted: 08/21/2016] [Indexed: 11/22/2022]
Abstract
Theoretical models are used to predict how breath-hold diving vertebrates manage O2, CO2, and N2 while underwater. One recent gas dynamics model used available lung and tracheal compliance data from various species. As variation in respiratory compliance significantly affects alveolar compression and pulmonary shunt, the current study objective was to evaluate changes in model output when using species-specific parameters from California sea lions (Zalophus californianus). We explored the effects of lung and dead space compliance on the uptake of N2, O2, and CO2 in various tissues during a series of hypothetical dives. The updated parameters allowed for increased compliance of the lungs and an increased stiffness in the trachea. When comparing updated model output with a model using previous compliance values, there was a large decrease in N2 uptake but little change in O2 and CO2 levels. Therefore, previous models may overestimate N2 tensions and the risk of gas-related disease, such as decompression sickness (DCS), in marine mammals.
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10
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Robertson HT. Dead space: the physiology of wasted ventilation. Eur Respir J 2014; 45:1704-16. [PMID: 25395032 DOI: 10.1183/09031936.00137614] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 09/29/2014] [Indexed: 11/05/2022]
Abstract
An elevated physiological dead space, calculated from measurements of arterial CO2 and mixed expired CO2, has proven to be a useful clinical marker of prognosis both for patients with acute respiratory distress syndrome and for patients with severe heart failure. Although a frequently cited explanation for an elevated dead space measurement has been the development of alveolar regions receiving no perfusion, evidence for this mechanism is lacking in both of these disease settings. For the range of physiological abnormalities associated with an increased physiological dead space measurement, increased alveolar ventilation/perfusion ratio (V'A/Q') heterogeneity has been the most important pathophysiological mechanism. Depending on the disease condition, additional mechanisms that can contribute to an elevated physiological dead space measurement include shunt, a substantial increase in overall V'A/Q' ratio, diffusion impairment, and ventilation delivered to unperfused alveolar spaces.
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Affiliation(s)
- H Thomas Robertson
- Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA
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11
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Butler JP, Tsuda A. Transport of gases between the environment and alveoli--theoretical foundations. Compr Physiol 2013; 1:1301-16. [PMID: 23733643 DOI: 10.1002/cphy.c090016] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The transport of oxygen and carbon dioxide in the gas phase from the ambient environment to and from the alveolar gas/blood interface is accomplished through the tracheobronchial tree, and involves mechanisms of bulk or convective transport and diffusive net transport. The geometry of the airway tree and the fluid dynamics of these two transport processes combine in such a way that promotes a classical fractionation of ventilation into dead space and alveolar ventilation, respectively. This simple picture continues to capture much of the essence of gas phase transport. On the other hand, a more detailed look at the interaction of convection and diffusion leads to significant new issues, many of which remain open questions. These are associated with parallel and serial inhomogeneities especially within the distal acinar units, velocity profiles in distal airways and terminal spaces subject to moving boundary conditions, and the serial transport of respiratory gases within the complex acinar architecture. This article focuses specifically on the theoretical foundations of gas transport, addressing two broad areas. The first deals with the reasons why the classical picture of alveolar and dead space ventilation is so successful; the second examines the underlying assumptions within current approximations to convective and diffusive transport, and how they interact to effect net gas exchange.
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Affiliation(s)
- James P Butler
- Harvard School of Public Health, Boston, Massachusetts, USA.
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Abstract
As early as the 6th century B.C. the Greeks speculated on a substance pneuma that meant breath or soul, and they argued that this was essential for life. An important figure in the 2nd century A.D. was Galen whose school developed an elaborate cardiopulmonary system that influenced scientific thinking for 1400 years. A key concept was that blood was mixed with pneuma from the lung in the left ventricle thus forming vital spirit. It was also believed that blood flowed from the right to the left ventricle of the heart through pores in the interventricular septum but this view was challenged first by the Arab physician Ibn al-Nafis in the 13th century and later by Michael Servetus in the 16th century. The 17th century saw an enormous burgeoning of knowledge about the respiratory gases. First Torricelli explained the origin of atmospheric pressure, and then a group of physiologists in Oxford clarified the properties of inspired gas that were necessary for life. This culminated in the work of Lavoisier who first clearly elucidated the nature of the respiratory gases, oxygen, carbon dioxide and nitrogen. At that time it was thought that oxygen was consumed in the lung itself, and the fact that the actual metabolism took place in peripheral tissues proved to be a very elusive concept. It was not until the late 19th century that the issue was finally settled by Pflüger. In the early 20th century there was a colorful controversy about whether oxygen was secreted by the lung. During and shortly after World War II, momentous strides were made on the understanding of pulmonary gas exchange, particularly the role of ventilation-perfusion inequality. A critical development in the 1960s was the introduction of blood gas electrodes, and these have transformed the management of patients with severe lung disease.
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Affiliation(s)
- John B West
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623, USA.
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Sonne C. Inequality of ventilation of different parts of the lung as a source of error in respiratory-physiological experiments. ACTA ACUST UNITED AC 2012. [DOI: 10.1111/j.1748-1716.1936.tb01560.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Swan AJ, Tawhai MH. Evidence for minimal oxygen heterogeneity in the healthy human pulmonary acinus. J Appl Physiol (1985) 2010; 110:528-37. [PMID: 21071589 DOI: 10.1152/japplphysiol.00888.2010] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
It has been suggested that the human pulmonary acinus operates at submaximal efficiency at rest due to substantial spatial heterogeneity in the oxygen partial pressure (Po(2)) in alveolar air within the acinus. Indirect measurements of alveolar air Po(2) could theoretically mask significant heterogeneity if intra-acinar perfusion is well matched to Po(2). To investigate the extent of intra-acinar heterogeneity, we developed a computational model with anatomically based structure and biophysically based equations for gas exchange. This model yields a quantitative prediction of the intra-acinar O(2) distribution that cannot be measured directly. Temporal and spatial variations in Po(2) in the intra-acinar air and blood are predicted with the model. The model, representative of a single average acinus, has an asymmetric multibranching respiratory airways geometry coupled to a symmetric branching conducting airways geometry. Advective and diffusive O(2) transport through the airways and gas exchange into the capillary blood are incorporated. The gas exchange component of the model includes diffusion across the alveolar air-blood membrane and O(2)-hemoglobin binding. Contrary to previous modeling studies, simulations show that the acinus functions extremely effectively at rest, with only a small degree of intra-acinar Po(2) heterogeneity. All regions of the model acinus, including the peripheral generations, maintain a Po(2) >100 mmHg. Heterogeneity increases slightly when the acinus is stressed by exercise. However, even during exercise the acinus retains a reasonably homogeneous gas phase.
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Affiliation(s)
- Annalisa J Swan
- Auckland Bioengineering Institute, The Univ. of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
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Lundsgaard C, Van Slyke DD. STUDIES OF LUNG VOLUME. I : RELATION BETWEEN THORAX SIZE AND LUNG VOLUME IN NORMAL ADULTS. ACTA ACUST UNITED AC 2010; 27:65-86. [PMID: 19868197 PMCID: PMC2125957 DOI: 10.1084/jem.27.1.65] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Affiliation(s)
- C Lundsgaard
- Hospital of The Rockefeller Institute for Medical Research
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Lundsgaard C. STUDIES OF OXYGEN IN THE VENOUS BLOOD : II. STUDIES OF THE OXYGEN UNSATURATION IN THE VENOUS BLOOD OF A GROUP OF PATIENTS WITH CIRCULATORY DISTURBANCES. ACTA ACUST UNITED AC 2010; 27:179-97. [PMID: 19868200 PMCID: PMC2125935 DOI: 10.1084/jem.27.2.179] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
1. Thirty-one determinations of the total oxygen-combining power and the oxygen in the venous blood from vena mediana cubiti of sixteen resting patients are reported. 2. The difference between the total oxygen capacity of the hemoglobin and the oxygen in the venous blood, the oxygen unsaturation, is calculated. 3. In twelve patients with compensated heart lesions the unsaturation was found within normal limits, between 2.5 and 8 volume per cent. 4. In four patients with incompensated heart disease the values for the unsaturation were all above the normal limit, from 9.7 to 15.2 volume per cent. 5. A general discussion of the problem of interpreting the results is given. 6. A comparison is drawn between the oxygen consumption calculated from direct determination of the blood flow on a normal subject (the writer) and the oxygen unsaturation determined 4 years later on the same subject. A close agreement between the two series of values exists.
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Affiliation(s)
- C Lundsgaard
- Hospital of The Rockefeller Institute for Medical Research
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ROELSEN EJNAR. Fractional analysis of alveolar air after inspiration of hydrogen as a method for the determination of the distribution of inspired air in the lungs. ACTA ACUST UNITED AC 2009. [DOI: 10.1111/j.0954-6820.1938.tb16399.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Tsuda A, Henry FS, Butler JP. Gas and aerosol mixing in the acinus. Respir Physiol Neurobiol 2008; 163:139-49. [PMID: 18396469 DOI: 10.1016/j.resp.2008.02.010] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2008] [Revised: 02/17/2008] [Accepted: 02/18/2008] [Indexed: 12/30/2022]
Abstract
This review is concerned with mixing and transport in the human pulmonary acinus. We first examine the current understanding of the anatomy of the acinus and introduce elements of fluid mechanics used to characterize the transport of momentum, gas and aerosol particles. We then review gas transport in more detail and highlight some areas of current research. Next we turn our attention to aerosol transport and in particular to mixing within the alveoli. We examine the factors influencing the level of mixing, review the concept of chaotic convective mixing, and make some brief comments on how mixing affects particle deposition. We end with a few comments on some issues unique to the neonatal and developing lung.
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Affiliation(s)
- Akira Tsuda
- Molecular and Integrative Physiological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
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Lindhard J. Circulation after cessation of work, with some remarks on the calculation of circulation rate experiments according to the nitrous oxide method. J Physiol 2007; 57:17-30. [PMID: 16993595 PMCID: PMC1405447 DOI: 10.1113/jphysiol.1922.sp002038] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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Sonne C. On the possibility of mixing the air in the lungs with foreign air, especially as it is used in Krogh and Lindhard's nitrous oxide method. J Physiol 2007; 52:75-87. [PMID: 16993413 PMCID: PMC1402697 DOI: 10.1113/jphysiol.1918.sp001822] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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Barcroft H. A source of error in measurement of the circulation rate by henderson and haggard's method. J Physiol 2007; 63:162-74. [PMID: 16993877 PMCID: PMC1514929 DOI: 10.1113/jphysiol.1927.sp002392] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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Darling RC, Cournand A, Richards DW, Domanski B. STUDIES ON INTRAPULMONARY MIXTURE OF GASES. V. FORMS OF INADEQUATE VENTILATION IN NORMAL AND EMPHYSEMATOUS LUNGS, ANALYZED BY MEANS OF BREATHING PURE OXYGEN. J Clin Invest 2006; 23:55-67. [PMID: 16695084 PMCID: PMC435317 DOI: 10.1172/jci101473] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- R C Darling
- Research Service, First Division, Welfare Hospital, New York City
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Hurtado A, Fray WW, Kaltreider NL, Brooks WD. STUDIES OF TOTAL PULMONARY CAPACITY AND ITS SUBDIVISIONS. V. NORMAL VALUES IN FEMALE SUBJECTS. J Clin Invest 2006; 13:169-91. [PMID: 16694200 PMCID: PMC435989 DOI: 10.1172/jci100576] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- A Hurtado
- Department of Medicine of the School of Medicine and Dentistry of the University of Rochester, Rochester, New York
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Abstract
This essay looks at the historical significance of an APS classic paper that is freely available online: Fowler WS. Lung function studies. II. The respiratory dead space. Am J Physiol 154: 405-416, 1948. ( http://ajplegacy.physiology.org/cgi/reprint/154/3/405 ).
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Loeppky JA, Caprihan A, Altobelli SA, Icenogle MV, Scotto P, Vidal Melo MF. Validation of a two-compartment model of ventilation/perfusion distribution. Respir Physiol Neurobiol 2005; 151:74-92. [PMID: 16024300 DOI: 10.1016/j.resp.2005.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2005] [Revised: 05/24/2005] [Accepted: 06/01/2005] [Indexed: 11/23/2022]
Abstract
Ventilation (V (A)) to perfusion (Q ) heterogeneity (V (A)/Q ) analyses by a two-compartment lung model (2C), utilizing routine gas exchange measurements and a computer solution to account for O(2) and CO(2) measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V (A)/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V (A)/Q distributions (SD(V (A)/Q )) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(V (A)/Q ) values. SD(V (A)/Q ) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V (A)/Q ) weighted by V (A) was closer to MC at higher values because the V (A)-weighted SD(V (A)/Q ) is related to blood-to-gas PCO(2) differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V (A)/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O(2) diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V (A)/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible.
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Affiliation(s)
- Jack A Loeppky
- Cardiology Section 111B, VA Medical Center, 1501 San Pedro Dr SE, Albuquerque, NM 87108, USA.
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Affiliation(s)
- John B West
- Department of Medicine, University of California San Diego, La Jolla, California, 92093-0623, USA.
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Mai VM, Liu B, Polzin JA, Li W, Kurucay S, Bankier AA, Knight-Scott J, Madhav P, Edelman RR, Chen Q. Ventilation-perfusion ratio of signal intensity in human lung using oxygen-enhanced and arterial spin labeling techniques. Magn Reson Med 2002; 48:341-50. [PMID: 12210943 DOI: 10.1002/mrm.10230] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
This study investigates the distribution of ventilation-perfusion (V/Q) signal intensity (SI) ratios using oxygen-enhanced and arterial spin labeling (ASL) techniques in the lungs of 10 healthy volunteers. Ventilation and perfusion images were simultaneously acquired using the flow-sensitive alternating inversion recovery (FAIR) method as volunteers alternately inhaled room air and 100% oxygen. Images of the T(1) distribution were calculated for five volunteers for both selective (T(1f)) and nonselective (T(1)) inversion. The average T(1) was 1360 ms +/- 116 ms, and the average T(1f) was 1012 ms +/- 112 ms, yielding a difference that is statistically significant (P < 0.002). Excluding large pulmonary vessels, the average V/Q SI ratios were 0.355 +/- 0.073 for the left lung and 0.371 +/- 0.093 for the right lung, which are in agreement with the theoretical V/Q SI ratio. Plots of the V/Q SI ratio are similar to the logarithmic normal distribution obtained by multiple inert gas elimination techniques, with a range of ratios matching ventilation and perfusion. This MRI V/Q technique is completely noninvasive and does not involve ionized radiation. A limitation of this method is the nonsimultaneous acquisition of perfusion and ventilation data, with oxygen administered only for the ventilation data.
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Affiliation(s)
- Vu M Mai
- Department of Radiology, Evanston Hospital, Evanston Northwestern Healthcare, Illinois, USA.
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DiCarlo SE, Bishop VS. Central baroreflex resetting as a means of increasing and decreasing sympathetic outflow and arterial pressure. Ann N Y Acad Sci 2001; 940:324-37. [PMID: 11458690 DOI: 10.1111/j.1749-6632.2001.tb03688.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The arterial baroreflex has two important functions. First, the arterial baroreflex is a negative feedback reflex that regulates arterial pressure around a preset value called a set or operating point. Second, the arterial baroreflex also establishes the prevailing systemic arterial pressure when the operating point is reset. That is, modulating the response of barosensitive neurons in the central nervous system (CNS) establishes the operating point or prevailing systemic arterial pressure. Therefore, the operating point of the arterial baroreflex is not fixed, but is variable over a wide range of pressures and is determined by a variety of inputs from the peripheral and central nervous systems. At the onset of dynamic exercise, heart rate (HR) and sympathetic nerve activity (SNA) increase abruptly and dramatically. The initial increase in HR and SNA is mediated by central command. Central command operates by resetting the operating point of the arterial baroreflex to a higher pressure. In this situation, the operating point of the arterial baroreflex is above the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by activating SNA and inhibiting parasympathetic nerve activity, which increases cardiac output and peripheral resistance and, consequently, arterial pressure. After exercise, loss of central command and enhanced activity of the cardiopulmonary reflex resets the operating point of the arterial baroreflex to a lower pressure. In this situation, the operating point of the arterial baroreflex is below the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by inhibiting SNA, which decreases peripheral resistance and consequently arterial pressure. In these situations, central resetting of the arterial baroreflex is a means of increasing and decreasing sympathetic outflow and arterial pressure.
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Affiliation(s)
- S E DiCarlo
- Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
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Abstract
Claude Gordon Douglas was born in Leicester on 26 February 1882, the son of Claude Douglas, F.R.C.S., Honorary Surgeon to the Leicester Royal Infirmary, and Louisa Bolitho Peregrine of London. His elder brother, J. S. G. Douglas, D.M., was Professor of Pathology at the University of Sheffield. Douglas was unmarried and for the last part of his life he lived with his younger sister, Miss Margaret Douglas, who died in 1960. Besides his father, both grandfathers and one great-grandfather were in medical practice and another great-grandfather was a keen student of natural history. From Arlington House, his preparatory school in Brighton, he won open scholarships in classics to Radley College, which he did not accept, and to Wellington College, which he accepted. He left Wellington College at the age of sixteen in order to study science at Wyggeston Grammar School, Leicester. In 1900 he went up to New College, Oxford, with an open exhibition in Natural Science (Biology) but in his first term won an open demyship in the same subject at Magdalen College, whither he migrated for the remainder of his time as an undergraduate. As an undergraduate he owed much to the personal friendship and encouragement of Professor Francis Gotch, F.R.S., and from an early stage he was especially influenced by the teaching of Dr J. S. Haldane, F.R.S. His undergraduate friendships with G. R. Girdlestone, later the eminent orthopaedic surgeon, and with A. S. (later Sir Arthur) MacNalty, were maintained throughout his life. MacNalty recounts how he provided notes on the professor’s five o’clock lectures for Douglas and Girdlestone when they were delayed on the golf course.
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Roca J, Wagner PD. Contribution of multiple inert gas elimination technique to pulmonary medicine. 1. Principles and information content of the multiple inert gas elimination technique. Thorax 1994; 49:815-24. [PMID: 8091330 PMCID: PMC475132 DOI: 10.1136/thx.49.8.815] [Citation(s) in RCA: 103] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
This introductory review summarises four different aspects of the multiple inert gas elimination technique (MIGET). Firstly, the historical background that facilitated, in the mid 1970s, the development of the MIGET as a tool to obtain more information about the entire spectrum of VA/Q distribution in the lung by measuring the exchange of six gases of different solubility in trace concentrations. Its principle is based on the observation that the retention (or excretion) of any gas is dependent on the solubility (lambda) of that gas and the VA/Q distribution. A second major aspect is the analysis of the information content and limitations of the technique. During the last 15 years a substantial amount of clinical research using the MIGET has been generated by several groups around the world. The technique has been shown to be adequate in understanding the mechanisms of hypoxaemia in different forms of pulmonary disease and the effects of therapeutic interventions, but also in separately determining the quantitative role of each extrapulmonary factor on systemic arterial PO2 when they change between two conditions of MIGET measurement. This information will be extensively reviewed in the forthcoming articles of this series. Next, the different modalities of the MIGET, practical considerations involved in the measurements and the guidelines for quality control have been indicated. Finally, a section has been devoted to the analysis of available data in healthy subjects under different conditions. The lack of systematic information on the VA/Q distributions of older healthy subjects is emphasised, since it will be required to fully understand the changes brought about by diseases that affect the older population.
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Affiliation(s)
- J Roca
- Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clinic, Barcelona, Spain
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Wagner PD, Rodriguez-Roisin R. Clinical advances in pulmonary gas exchange. THE AMERICAN REVIEW OF RESPIRATORY DISEASE 1991; 143:883-8. [PMID: 2009000 DOI: 10.1164/ajrccm/143.4_pt_1.883] [Citation(s) in RCA: 57] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- P D Wagner
- Department of Medicine, University of California San Diego, La Jolla
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Neufeld GR, Gobran S, Baumgardner JE, Aukburg SJ, Schreiner M, Scherer PW. Diffusivity, respiratory rate and tidal volume influence inert gas expirograms. RESPIRATION PHYSIOLOGY 1991; 84:31-47. [PMID: 1852988 DOI: 10.1016/0034-5687(91)90017-d] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
We modified, and developed software for, a computer-controlled quadrupole mass spectrometer to measure complete breath-by-breath expirograms of helium (He) and sulfur hexafluoride (SF6) exhaled during the infusion of saline saturated with the inert gases. He and SF6 have similar blood solubilities but very different gas phase diffusivities allowing examination of the influence of gas phase diffusivity on steady state inert gas expirograms. We studied six normal human volunteers in nine separate studies and examined the influence of tidal volume (VT) and breathing frequency (f) on the airways dead space (VDaw) and alveolar plateau slope (phase III) for the inert gases and CO2. The experimental data showed a reduction in VDaw with rapid shallow breathing, while phase III slope increased by a factor of two to three. We critically evaluated the data and methodology of these and previously reported studies of continuous and single breath washout of He and SF6. In general the 15 to 20 ml differences in VDaw between He and SF6 were in keeping with previous studies by others. The ratio of phase III slopes of SF6 to He reported by us previously (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988) was 3.13. In the current study, which includes the analysis of more than 400 He and SF6 breaths, the ratio of SF6 to He slope was 1.85. The difference between the two studies was largely related to the improved methodology of the current study, particularly for the measurement of He. The results support the conclusion that diffusivity is an important component of both phase II and phase III of the expirogram. However, the difference in phase III between He and SF6 is somewhat less than previously reported.
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Affiliation(s)
- G R Neufeld
- Department of Anesthesia, School of Medicine, University of Pennsylvania, Philadelphia
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Abstract
The effects of alterations in ventilatory pattern on the simultaneously measured physiologic and anatomic dead-spaces (VDphys and VDan, respectively) and the dead-space to tidal volume ratio (VD-VT) were studied in 17 healthy normal subjects (13 men, four women, ages 21 to 36 years). There were no significant changes in VDan with increases in respiratory frequency (f) or tidal volume (VT). The VDphys increased (mean change +0.153 L, p less than 0.05) with increase in VT (mean increase +0.84 L, p less than 0.01), but did not alter significantly with a twofold increase in f, at control VT. Increase in VT significantly reduced VD/VT (mean change -10.4 percent, p less than 0.05), but increase in f, at control VT, did not significantly alter VD/VT. These results indicate that in normal subjects, increase in VT alters ventilation/perfusion matching in the lungs, whereas an increase in f, at constant VT, has no effect on ventilation/perfusion matching. Increases in VD/VT cannot, therefore, be ascribed to alterations in ventilatory pattern where either VT, or f, or both are increased.
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Affiliation(s)
- R W Baker
- Department of Medicine, University of Kentucky Medical Center, Lexington
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Zwart A, Luijendijk SC, de Vries WR. Excretion-retention data of steady state gas exchange in tidal breathing. II. Dependency on the diffusion coefficient. Pflugers Arch 1986; 407:211-5. [PMID: 3748782 DOI: 10.1007/bf00580678] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The steady state gas transfer properties of the lung can be derived from excretion-retention (E-R) data of inert tracer gases that are infused intravenously. E = PE/Pv and R = Pa/Pv, where PE, Pa and Pv represent the partial pressures of the tracer gases in mixed expired gas, arterial blood and mixed venous blood, respectively. In this paper, we investigate the influence of diffusive gas mixing in the lung on E and R. To that end, E-R data sets were simulated with a lung model that takes into account tidal breathing, the morphometric geometry of the airways, diffusion limited gas mixing in the alveolar space and gas dissolved in superficial lung tissue. The results show a linear relationship between R/E and D-0.5, where D represents the diffusion coefficient of the tracer gases in the alveolar gas mixture. This is in contrast to the results of simulations with a lung model that describes the different gas transport mechanisms, including diffusion, as a constant rate process, where a linear relationship between R/E and D-1 is predicted. It is further shown that E-R data of helium and sulphur hexafluoride cannot be used to demonstrate diffusion limited gas mixing in the lung, in particular, in the presence of a real shunt fraction. For that purpose, excretion data of pairs of tracer gases with different D but equal, medium blood-gas partition coefficients (1 less than lambda less than 30) should be used. For such pairs of tracer gases, the E values may differ by more than 10% when the D values for the two gases are 0.22 and 0.1 cm2s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Abstract
In order to calculate alveolar deadspace, an important measure of ventilation/perfusion mismatching, it is necessary to measure airway or anatomical deadspace (VDaw) and physiological deadspace. VDaw is usually measured graphically or by similar means, but sometimes it is estimated from a formula, based on Christian Bohr's work, in which end-tidal PCO2 is used as a measure of alveolar PCO2. In 58 patients undergoing anaesthesia and positive pressure ventilation, there were large errors in this estimate of VDaw compared to a graphical method. At tidal volumes of 400-500 ml, the median error was 34 ml; at larger tidal volumes, the median error increased to 74 ml (P less than 0.001). The size of the error was correlated to the slope of phase III, the part of the CO2 tracing representing alveolar CO2, at both ventilator settings (P less than 0.01). It is concluded that estimates of VDaw based on end-tidal PCO2 are unreliable, and their use will lead to a large part of the alveolar deadspace being wrongly accredited to VDaw.
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Paiva M, van Muylem A, Ravez P, Yernault JC. Inspired volume dependence of the slope of the alveolar plateau. RESPIRATION PHYSIOLOGY 1984; 56:309-25. [PMID: 6473945 DOI: 10.1016/0034-5687(84)90067-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Two series of experiments were performed in nine healthy subjects. In series I, 96 single breath tests were performed in two subjects. The inspired gas contained 90% O2, 5% He and 5% SF6 and the slope of the alveolar plateau for N2, He and SF6 was computed. The following experimental conditions were considered variable: inspired volume with preinspiratory lung volume equal to residual volume or functional residual capacity (FRC), both with and without 10 sec breath-holding. In series II, each of the other 7 subjects performed 12 single breath N2 tests in which the subject inspired both 1 L and an inspiratory capacity (IC) of O2 from FRC with without 10 sec breath-holding. The main experimental observation is that without breath-holding the absolute value of the slope of the alveolar plateau is larger for 1 L inspiration than for an IC inspiration, whereas this volume dependence was smaller after 10 sec of breath-holding. Based on Milic-Emili model of the lung and on simulations of a multibranch point model of the acinus we concluded that, in so far as these models adequately describe gas distribution in the lung, intraregional parallel units presenting a sequential convective flow play an important role in the genesis of the alveolar plateau.
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D'Alonzo GE, Dantzker DR. Respiratory failure, mechanisms of abnormal gas exchange, and oxygen delivery. Med Clin North Am 1983; 67:557-71. [PMID: 6843220 DOI: 10.1016/s0025-7125(16)31189-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Patients with respiratory failure may have abnormal gas exchange based on a number of mechanisms. Each of these mechanisms may indicate a different underlying pathology and thus suggest different therapeutic interventions. In addition, the ability to monitor changes in physiologic function can be complicated but is achievable when proper protocols are followed. It should be clear that an adequate understanding of the underlying physiology is crucial to the successful management of these very difficult patients.
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Ben Jebria A, Bres M. Computer simulation of ternary diffusion in distal airways of the human lung. INTERNATIONAL JOURNAL OF BIO-MEDICAL COMPUTING 1982; 13:403-19. [PMID: 7129668 DOI: 10.1016/0020-7101(82)90005-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Gaseous diffusion plays a fundamental role in the terminal generations of airways for respiratory physiology. It has been proposed as a prime mechanism underlying stratified inhomogeneity in the alveolar space. Nevertheless, the diffusion phenomenon in the lung has often been studied using Fick's law which is only valid for binary diffusion. Under conditions of more than two gases in a mixture, the appropriate equations for diffusion are those of Stefan. In respiration, diffusion involves at least three gases (O2, CO2 and N2), and in physiological experiments complex mixtures including heavy or light gases (SF6, He) are often added to enhance the effect of diffusion. We present in this paper the features of ternary diffusion and solve the appropriate equations for the non-steady state by a finite difference method. The simulation was performed using two models derived from the anatomical data of Weibel and Hansen-Ampaya. Moreover, four initial conditions most often encountered during current respiratory physiology tests, were used for the computations. Therefore in these four situations, O2-N2-He, O2-N2-Ar, O2-N2-SF6 and O2-N2-CO2 combinations were used. Our results showed that for each case mentioned above the oxygen acted differently in ternary diffusion owing to the specific nature of the components of each mixture. Moreover, the behaviour of each component in ternary diffusion was very different from that of binary diffusion. However, this difference may be negligible when the subject breathed normal air.
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Abstract
We simulated sequential filling and emptying of a lung lobe (Fukuchi et al., 1980) by solving a differential equation for simultaneous convection and diffusion within a solid expansile model of an asymmetrical acinus. For a given degree of asymmetry subtended at a fixed branch point the shorter units are consistently better ventilated (by diffusion) despite homogeneous lung expansion. Thus a helium bolus inhaled at 80% of vital capacity (VC) results in a higher helium concentration (FHe) at full inflation within the shorter units. A bolus inhaled at 20% VC results in relatively greater FHe in longer units. On expiration diffusive interaction between parallel pathways at the branch point results in a range of alveolar plateaus whose slope varies inversely with the volume at which the helium bolus is inhaled. This interdependence of gas transport among parallel pathways contributes to the "first in-last out' pattern observed experimentally. Comparison of radially expansile with axial-radially expansile models does not produce qualitatively significant differences. However, equilibration of gas concentrations during breathholding in the model occurs more rapidly than under experimental conditions indicating that other mechanisms may also contribute to the observed pattern of lung filling and emptying.
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Abstract
We examined the influence of asymmetry on the interaction of convection and gas-phase diffusion within the acinus of the lung. Single breaths of O2 were simulated by solving a differential equation for gas transport in two trumpet shaped units which were joined at a branch point and whose relative lengths and volumes were made to vary. Despite synchronous bulk flow to the from the units, in proportion to their relative volumes, the shorter unit always reached a higher O2 concentration (FO2) at end inspiration. Interdependence of gas transport at the branch point resulted in a falling FO2 within the shorter unit during expiration. The FO2 at the exit of the model therefore decreased progressively throughout expiration, simulating a sloping alveolar plateau. The simulations suggest that despite the relatively short distances separating parallel intra-acinar pathways, convective-diffusive interactions in the presence of asymmetry may produce substantial inhomogeneity in alveolar gas concentrations. Furthermore, the slope of the N2 plateau in the normal mammalian lung is explicable on the basis of the asymmetrical airway anatomy and well defined physical processes.
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Scherer PW, Haselton FR. A network theory of bronchial gas mixing applied to single breath nitrogen washout. Lung 1980; 158:201-20. [PMID: 7464212 DOI: 10.1007/bf02713724] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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