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On October 24, 1981, Chris Pizzo and Yong Tenzing, members of the American Medical Research Expedition to Mt Everest (AMREE), stood on the highest point on earth and collected 6 alveolar gas samples. These, together with further data collected from the South Col (8050 m), provided the foundations for what is surely one of the most unique field experiments ever undertaken—the calculation of arterial blood gases from a mountaineer on the summit of Mt Everest (8848 m; Table). Without the accurate portable blood gas analyzers that many of us now take for granted, the AMREE team used the ‘‘Bohr Integration,’’ a complex computational method used primarily to calculate the diffusion capacity of oxygen inside the human lungs. By assuming this value, the AMREE team was able to calculate the mean alveolar-capillary PO2 difference and therefore deduce the PO2 of arterial blood. However, to complete this, a long list of measurements and assumptions would need to be made first, and it is this attention to detail that makes ‘‘Pulmonary Gas Exchange on the Summit of Mt Everest’’ such an exceptional piece of work.1 In what Edouard Wyss Dunant, the leader of the unsuccessful 1952 Swiss Expedition to Mt Everest, once described as the ‘‘todeszone’’ or ‘‘death zone,’’ the AMREE team conducted an unparalleled set of tests. Not only did they record the first accurate barometric pressure reading on the summit of Mt Everest, but they were also able to obtain 42 resting alveolar gas samples from various sites above 8000 m (Figure 1). These results showed, for the first time, the dramatic fall in alveolar

The 13C breath test is a method of clarifying the metabolism of loaded substances by administering 13C-labelled materials and calculating the 13CO2 and 12CO2 ratio (13C/12C isotope ratio) in the expired gas. The materials are metabolized and expelled in the expired gas. Because simultaneous continuous measurement of 13CO2 and 12CO2 in expired gas has been difficult up to the present, respective expired gases, including dead space before and after administration, have been sampled to separate sampling bags and 13C/12C has been measured in the bags and changed fraction of 13C/12C after administration (delta) has been used to judge the metabolic process. This method is affected by the contamination of the dead space gas. In the present study, in order to exclude the dead space effect, simultaneous continuous analysis of 12CO2 and 13CO2 of expired gas identifying alveolar gas was applied to the 13C-urea breath test in addition to the conventional sampling bag method. Both isotope detectors were attached to a mass spectrometer. Fifty-six cases receiving stomach health check-ups for Helicobacter pylori were examined. Delta was calculated in the bag or in phase III of continuous gas measurement. Because the bag contains dead space, delta was reduced and sensitivity and specificity with reference to gastric fluoroscopy or Helicobacter pylori IgG antibody were reduced. Decreasing the dead space contamination is important in reducing the measurement error in the 13C breath test and simultaneous continuous measurement is a good tool for this purpose.

BACKGROUND: Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSMmanoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer.OBJECTIVE: To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity.PARTICIPANTS AND DESIGN: Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates.METHODS: Both smokers and nonsmokers performed SBWSMmanoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix).RESULTS: For SBWSM, DIwas increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DIwith breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVCmanoeuvres, there were no differences due to smoking in Sn or Emix, but DIwas increased in smokers and correlated with age and smoking pack-years, but not with Sn.CONCLUSIONS: For SBWSMmanoeuvres the increase in DIin smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DIreflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVCmanoeuvres, the increase in DIin smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DIduring this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

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.

The sections in this article are: 1 Barometric Pressure 2 Pulmonary Gas Exchange 2.1 Alveolar Gas Composition 2.2 Blood Gases and Acid-Base Status 3 Maximal Oxygen Consumption 4 Cardiovascular System 5 Other Features 5.1 Central Nervous System 5.2 Sleep 5.3 Metabolic Changes

Conventional methods of measuring the single breath diffusing capacity of the lung for carbon monoxide (DLcoSB) are based on the Krogh equation, which is valid only during breath holding. Rigid standardization is used to approximate a pure breath hold manoeuvre, but variations in performing the manoeuvre cause errors in the measurement of DLcoSB. The authors previously described a method of measuring DLcoSBusing separate equations describing carbon monoxide uptake during each phase of the manoeuvre: inhalation, breath holding and exhalation. The method is manoeuvre-independent, uses all of the exhaled alveolar gas to improve estimates of mean DLcoSBand lung volume, and is more accurate and precise than conventional methods. A slow, submaximal, more physiological single breath manoeuvre can be used to measure DLcoSBin patients who cannot achieve the flow rates and breath hold times necessary for the standardized manoeuvre. The method was initially implemented using prototype equipment but commercial systems are now available that are capable of implementing this method. The authors describe how to implement the method and discuss considerations to be made in its use.

It has recently been shown that the acinus can have a reduced efficiency due to a “screening effect” governed by the ratio of oxygen diffusivity to membrane permeability, the gas flow velocity, as well as the size and configuration of the acinus. We present here a top to bottom calculation of the functioning of a machine acinus at exercise that takes this screening effect into account. It shows that, given the geometry and the breathing dynamics of real acini, respiration can be correlated to a single equivalent parameter that we call the integrative permeability. In particular we find that both V ˙ O 2 ,max and P A O 2 depend on this permeability in a non-linear manner. Numerical solutions of dynamic convection–diffusion equations indicate that only a narrow range of permeability values is compatible with the experimental measurements of P A O 2 and V ˙ O 2 ,max . These permeability values are significantly smaller than those found in the literature. In a second step, we present a new type of evaluation of the diffusive permeability, yielding values compatible with the top to bottom approach, but smaller than the usual morphometric value.

The carbon dioxide (CO2) trace versus time (time capnography) is convenient and adequate for clinical use. This is the method most commonly utilized in capnography. However, the current terminology in time capnography has not yet been standardized and is, therefore, a potential source of confusion. Standard terminology that is based on convention and logic to represent the various phases of a time capnogram is essential. The time capnogram should be considered as two segments: an inspiratory segment and an expiratory segment. The inspiratory segment is termed as phase ); the expiratory segment is divided into phases I, II, III, and, occasionally, IV. Phase I represents the CO2-free gas from the airways (anatomical dead space); phase II consists of a rapid S-shaped upswing on the tracing due to mixing of dead space gas with alveolar gas; and phase III, the alveolar plateau, represents CO2-rich gas from the alveoli. The physiologic basis of phase IV, the terminal upswing at the end of phase III, which is observed in capnograms recorded under certain circumstances (such as in pregnant subjects and obese subjects) is discussed in detail. The clinical implications of the alpha angle, which is the angle between phases II and III, and the beta angle, which is the angle between phases III and the descending limb of phase 0, are outlined. The subtle but important limitations of time capnography are reviewed; its current status as well as its future potential are explored.

In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

The presence of differences in physiological response to a lowered inspired Po2 mediated by hypobaric hypoxia (HH) or normobaric hypoxia (NH) is controversial. This review examines the brief, acute, and subacute respiratory, cardiovascular, and subjective symptom response to intermediate and severe hypoxic exposure in NH and HH. Brief exposures lead to similar physiological responses; this is not the case in acute/subacute exposures. Extrapolating data from NH studies to HH in longer exposures is inappropriate as physiological responses to hypoxia seem to be influenced by the prevailing ambient pressure, especially in chronic exposures where acute mountain sickness severity is greater in HH than NH. Explanations for the discrepancy between the two modalities include differences in ventilatory patterns, alveolar gas disequilibrium, and dissimilar acute hypoxic ventilatory responses. Awareness and consideration of these key differences between NH and HH is essential to their proper application to kinesiology, altitude, and aviation medicine.

Halothane minimum alveolar concentration (MAC)-sparing response is preserved in rats rendered tolerant to the action of dexmedetomidine. It has been shown that halothane and isoflurane act at different sites to produce immobility. The authors studied whether there was any difference between halothane and isoflurane MAC-sparing effects of dexmedetomidine in rats after chronic administration of a low dose of this drug. Twenty-four female Wistar rats were randomly allocated into four groups of six animals: two groups received 10 μg/kg intraperitoneal dexmedetomidine for five days (treated groups) and the other two groups received intraperitoneal saline solution for five days (naive groups) prior to halothane or isoflurane MAC determination (one treated and one naive group of halothane and one treated and one naive group of isoflurane). Halothane or isoflurane MAC determination was performed before (basal) and 30 min after an intraperitoneal dose of 30 μg/kg of dexmedetomidine (post-dex) from alveolar gas samples at the time of tail clamp. Administration of an acute dose of dexmedetomidine to animals that had chronically received dexmedetomidine resulted in a MAC-sparing effect that was similar to that seen in naive animals for halothane; however, the same treatment increased the MAC-sparing response of dexmedetomidine for isoflurane. Isoflurane but not halothane MAC-sparing response of acutely administered dexmedetomidine is enhanced in rats chronically treated with this drug.

The main function of the lung is to exchange respiratory gases, oxygen and carbon dioxide. In order to achieve this it has a huge surface area (equivalent to the size of a tennis court in the fully mature adult) and a remarkably thin barrier between the capillary blood and alveolar gas. 1 However the entrance to this large exchanging surface is relatively small z and it is obstruction to the conducting airways that causes most respiratory morbidity in childhood. When a respiratory problem is clinically obvious or is suspected, the measurement of lung function has a role in (a) identifying or characterising the problem, (b) assessing the disease severity and (c) assessing disease progression and response to treatment. Measurements of lung function have also improved our understanding of the growth and development of the respiratory system. 3'4

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 (Po2) in alveolar air within the acinus. Indirect measurements of alveolar air Po2 could theoretically mask significant heterogeneity if intra-acinar perfusion is well matched to Po2. 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 O2 distribution that cannot be measured directly. Temporal and spatial variations in Po2 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 O2 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 O2-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 Po2 heterogeneity. All regions of the model acinus, including the peripheral generations, maintain a Po2 >100 mmHg. Heterogeneity increases slightly when the acinus is stressed by exercise. However, even during exercise the acinus retains a reasonably homogeneous gas phase.

A common method for analyzing a multibreath nitrogen washout (MBNW) is to perform moment analysis and derive the mean dilution number (MDN). A homogeneously mixed alveolar space with zero series dead space (VD = 0) will always result in a MDN = 1, regardless of breathing pattern. A higher MDN implies more inhomogeneity. But, if VD greater than 0, the MDN can become sensitive (artificially high) to VD/VT ratios. We present an alveolar-based mean dilution number (AMDN) that uses the cumulative expired alveolar volume. Unlike the MDN, the AMDN for a homogeneously mixed alveolar space is unity, regardless of VD or VT, and hence should be a more appropriate index of inhomogeneity at the alveolar level. Two sets of experiments were used to compare the AMDN with the MDN. First, a MBNW was performed by five healthy subjects at spontaneous VD/VT and at a low VD/VT achieved by a controlled increase in VT. Here, the MDN decreased from 1.98 +/- 0.1 to 1.79 +/- 0.06, whereas the AMDN was essentially unchanged (1.42 +/- 0.04 to 1.38 +/- 0.06). Second, MBNW values from seven healthy subjects, five with cystic fibrosis, and 10 asthmatic subjects (before and after bronchodilation) were analyzed. Compared with the MDN, the AMDN showed a significantly wider separation between clinical groups. Also, the AMDN demonstrated an increased variability within both sick groups versus a decrease in the healthy group. We conclude that the AMDN is superior to the MDN because of its decreased sensitivity to breathing pattern but increased sensitivity to degree of disease.

The lumped six-element model of the respiratory system proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) has often been used to analyze respiratory system impedance (Zrs) data. This model predicts a resonance (relative minimum in Zrs) at fr between 6 and 10 Hz and an antiresonance (relative maximum in Zrs) at far at higher frequencies (greater than 64 Hz). The far is due to the lumped tissue inertance (Iti) and the alveolar gas compression compliance (Cg). An fr and far have been recently reported in humans, but the far was shown to be not related to Iti and Cg, but instead it is the first acoustic antiresonance of the airways due to their axial dimensions). Zrs data to frequencies high enough to include the far have not been reported in dogs. In this study, we measured Zrs in dogs for frequencies between 5 and 320 Hz and found an fr at 7.5 +/- 1.6 Hz and two far at 97 +/- 13 and 231 +/- 27 Hz (far,1 and far,2, respectively). When breathing 80% He-20% O2, the fr shifted to 14 +/- 2 Hz, far,1 did not change (98 +/- 9 Hz), and far,2 increased to greater than 320 Hz. The behavior of fr and far,1 is consistent with the structure-function implied by the six-element model. However, the presence of an far,2 is not consistent with this model, because it is the airway acoustic antiresonance not represented in the model. These results indicate that, for frequencies that include the fr and far,1, the six-element model can be used to analyze Zrs data and reliable estimates of the model's parameters can be extracted by fitting the model to the data. However, more complex models must be used to analyze Zrs data that include far,2.

Although the Oxford Conferences began in 1978 as a result of the inspiration of Dan Cunningham and others at the University Laboratory of Physiology in Oxford, the roots of the meetings can be traced to John Scott Haldane (1860-1936) and his colleagues at the turn of the century. Indeed, the Laboratory (or its predecessor) has had an exemplary persistence (some might say an obsession) with the role of oxygen and, particularly, carbon dioxide in the control of breathing for over 100 years. An early key paper was that by Haldane and J.G. Priestley in 1905, "The regulation of the lung ventilation," where careful measurements of the Pco2 in alveolar gas under a variety of conditions showed its critical role in control. But, Haldane was a man of very wide interests and enormous energy, and he made many other contributions, some of which are discussed here. On the one hand, he had an intense interest in very practical issues, for example, the dangers of mine gases and, on the other, he had a distinctly philosophical, vitalist bent which colored his views of physiology.

A capnogram measures the concentration of carbon dioxide in the inspired and expired gas (in mmHg, kPa or vols %). For descriptive purposes it is often represented in an idealised form in text books. Figure 1 charts the theoretical changes in carbon dioxide (COz) concentration with time over a respiratory cycle. The almost vertical line PQ denotes the sudden increase in CO2 that occurs as alveolar gas enters the capnograph and the nearly horizontal plateau QR represents the CO2 concentration in the alveolar gas. The concentration at R is termed the end-tidal partial pressure of COz (&co~). At some time, just before or at R, inspiration begins and the flow in the breathing system changes direction. The exact time at which inspiration begins cannot be determined from the capnogram without a simultaneous flow signal or a knowledge of the circuit geometry because the first part of the inspired breath which passes the sampling site may well be alveolar gas from the end of expiration. Under these conditions the ‘plateau’ level of expired gas continues to be recorded even though inspiration is occurring. Once inspiration has started fresh gas soon replaces the alveolar gas at the sampling port and the concentration of COz falls rapidly to S. The horizontal line SP represents the concentration of CO:! in the inspired gas (P$oz). At some point between S and P inspiration ends, the flow reverses, and expiration begins. A flow signal is always required for the precise identification of the end of inspiration

BackgroundIt has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC.MethodsForty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MACISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg).ResultsThe control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MACISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively.ConclusionsThe administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MACISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.

Conway (1985) described the geometry of the Mapleson classification and the behaviour of the breathing systems under conditions of spontaneous and controlled respiration. The Mapleson A (Magill) system (Figure 48) has the fresh gas inlet remote from the subject while the expiratory valve is near the subject. Dead space is shown as the shaded area. This makes the system particularly economic to use during spontaneous respiration . Figure 49 shows the hypothetical pressure and flow inside the Mapleson A system during expiration. Flow during expiration, which is usually a passive process, is maximal at the beginning of expiration, and it falls off exponentially. Pressure inside the system rises exponentially but at a faster rate than the expiratory flow falls because of accumulation of fresh gas in the system; this rise in pressure is cut off when the expiratory valve opens at 5–6 kPa and this pressure is then maintained until end-expiration. Areas under the flow curve give expired volumes (see the chapter on flow and volume measurement); dead space gas ( V D ), which is identical in composition to fresh gas is expired first until point A on the graph. When the expiratory valve opens at point B, alveolar gas ( V A ) beyond that point is vented out. Furthermore, alveolar gas that was deposited inside the system between points A and B (start of alveolar gas expiration and opening of expiratory valve) is after the opening of expiratory valve being pushed out by the fresh gas inflow ( V F ).

Background Climbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later. Results A preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m – 4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO2 4.0 kPa (30 mmHg), PCO2 1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO2 +0.3 to +0.4 kPa (+2 to +3 mmHg), PCO2 0 to +0.13 kPa (+1 mmHg), pH -0.02 to -0.04, base excess -0.7 to -1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO2 is presumably caused mainly by contamination of the blood with air. Conclusion We conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small.

A single compartment model has been used to describe the dynamic respiratory mechanics in 21 newborn infants. The subjects were intubated and studied during mechanical ventilation. A whole-body plethysmograph was used to record the ventilatory flow. The estimated resistance and compliance values of the respiratory system have been compensated for the effect of alveolar gas compression. The average compensated resistance value was 11% lower than the uncompensated value and the average compensated compliance value was 6% higher than the uncompensated value.

The volume of O2 exchanged at the mouth during a breath (Vo2,m) is equal to that taken up by pulmonary capillaries (Vo2,A) only if lung O2 stores are constant. The latter change if either end-expiratory lung volume (EELV), or alveolar O2 fraction (FaO2) change. Measuring this requires breath-by-breath (BbB) measurement of absolute EELV, for which we used optoelectronic plethysmography combined with measurement of O2 fraction at the mouth to measure Vo2,A = Vo2,m - (ΔEELV·FaO2 + EELV·ΔFaO2), and divided by respiratory cycle time to obtain BbB O2 consumption (V̇o2) in seven healthy men during incremental exercise and recovery. To synchronize O2 and volume signals, we measured gas transit time from mouthpiece to O2 meter and compared V̇o2 measured during steady-state exercise by using expired gas collection with the mean BbB measurement over the same time period. In one subject, we adjusted the instrumental response time by 20-ms increments to maximize the agreement between the two V̇o2 measurements. We then applied the same total time delay (transit time plus instrumental delay = 660 ms) to all other subjects. The comparison of pooled data from all subjects revealed r2 = 0.990, percent error = 0.039 ± 1.61 SE, and slope = 1.02 ± 0.015 (SE). During recovery, increases in EELV introduced systematic errors in V̇o2 if measured without taking ΔEELV·FaO2+EELV·ΔFaO2 into account. We conclude that optoelectronic plethysmography can be used to measure BbB V̇o2 accurately when studying BbB gas exchange in conditions when EELV changes, as during on- and off-transients.

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 ± 18%) than for LP (5 ± 4%) and NP (1 ± 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 ± 0.09) than for LP (0.96 ± 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 ± 0.26) than for LP (0.05 ± 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.

Alveolar gas transfer over a given breath (i) was determined in ten subjects at rest and during steady-state cycling at 60, 90 or 120 W as the sum of volume of gas transferred at the mouth plus the changes of the alveolar gas stores. This is given by the gas fraction (FA) change at constant volume plus the volume change (ΔVAi) at constant fraction i.e. VAi-1(FAi-FAi-1)+FAi·ΔVAi, where VAi–1 is the end-expiratory volume at the beginning of the breath. These quantities, except for VAi–1, can be measured on a single-breath (breath-by-breath) basis and VAi–1 set equal to the subject's functional residual capacity (FRC, Auchincloss model). Alternatively, the respiratory cycle can be defined as the interval elapsing between two equal expiratory gas fractions in two successive breaths (Gronlund model G). In this case, \( F_{t_{\rm 1} } = F_{t_{\rm 2} } \) and thus the term VAi–1 (FAi–FAi–1) vanishes. In the present study, average alveolar O2 uptake (\( \mathop V\limits^ \bullet {\rm O}_{{\rm 2}{\rm ,A}} \) ) and CO2 output (\( \mathop V\limits^ \bullet {\rm CO}_{{\rm 2}{\rm ,A}} \) ) were equal in both approaches whereby the mean signal-to-noise ratio (S/N) was 40% larger in G. Other approaches yield steady state S/N values equal to that obtained in G, although they are based on the questionable assumption that the inter-breath variability of alveolar gas transfer is minimal. It is concluded that the only promising approach for assessing "true" single-breath alveolar gas transfer is that originally proposed by Gronlund.

Preoperative analgesics are being increasingly used to provide analgesia in the intraoperative and postoperative period. Opioids reduce anaesthetic requirements, although the effect varies with the different drug and species. The aim of this work was to determine whether buprenorphine reduces the minimum alveolar concentration (MAC) of isoflurane in a dose-related fashion, and whether this effect is similar to morphine when clinical doses of both drugs are used in the rat. Thirty-six male Wistar rats were anaesthetized with isoflurane, and MAC was determined before and after the administration of either buprenorphine or morphine. MAC of isoflurane was determined from alveolar gas samples when a standard noxious stimulus, in the form of a tail clamp, was applied. The duration and degree of reduction of the MAC of isoflurane were recorded. Basic cardiovascular and respiratory measurements were also recorded. Buprenorphine (10, 30 and 100 μg/kg) and morphine (1, 3 and 10 mg/kg) reduced in a dose-dependent fashion the MAC of isoflurane by 15%, 30% and 50%, respectively. Buprenorphine resulted in less cardiovascular and respiratory depression and had a longer-lasting action than morphine. In conclusion, buprenorphine has a dose-related isoflurane sparing effect in the rat similar to that caused by morphine at clinical doses of both drugs.

The single path model of airway gas transport was incorporated into each of the seven parallel regions model of Cruz (Cruz, J. C. Respir. Physiol. 86:1–14, 1991). Thus, the effect of time on the predicted gas fractions in and out of the lung could be evaluated. Two experimental maneuvers were simulated: (1) fast inhalation of an argon–oxygen mixture from a functional residual capacity and fast exhalation to residual volume, including inspiratory breath holdings of 5–20 s, and (2) the standard single-breath nitrogen washout test. Expired argon and nitrogen are predicted within a ±3% error of the experimental data with no breath holding. Breath holding predictions were at variance with experimental results because the solution of the diffusion-convection equation produced even mixing in the alveoli at the end of inspiration. The minimum square of the difference between the experimental data (standard single-breath nitrogen washout test) and those provided by the model was 0.0016. This model is capable of generating a nitrogen expirogram with four phases when a vital capacity of oxygen is inhaled. However, the model failed to produce a sharp distinction between phase 3 and phase 4. Thus, we conclude that uneven emptying of parallel regions generates any expirogram (a fast or slow expiratory maneuver). The alveolar gas stratification that is created during inspiration disappears at the end of the inspiratory maneuver. As a result, breath holding maneuvers cannot be predicted in the anatomical model used. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8710+e

the structure of the pulmonary blood to alveolar gas barrier represents a compromise between conflicting functional requirements: thin enough for adequate oxygen exchange, yet strong enough to resist the mechanical stress imposed as vascular volume and/or alveolar volume is expanded. The thinness of

Capnography permits recognition of CO2 concentration changes in the patient’s airway during the respiratory cycle. The capnogram represents total CO2 eliminated by the lungs, given that no gas exchange occurs in the airways. Expired gas contains CO2 from three sequential compartments: phase I contains gas from apparatus and anatomic dead space, phase II represents increasing CO2 concentration resulting from progressive emptying of alveoli, and phase III represents essentially alveolar gas. The highest point is the end-tidal PCO2 [1–4].

In the course of studying gas exchange during partial liquid ventilation (PLV) in healthy and injured piglets, we noted a reversal in the profile of exhaled CO2 (PECO2) versus time. Rather than a positive slope, the CO2 expirogram often reached a peak early in expiration and fell toward the end of the breath. In addition to a change in sign, the absolute value of the slope was very large. The change in profile led us to question the generally accepted practice of using “end-tidal” PECO2 to represent average alveolar PACO2 during PLV. Given the steep rate of change of PECO2 over a breath, the use of a single point on the CO2 expirogram to represent alveolar gas during PLV seemed in error. We hypothesized that a combination of increased ventilation heterogeneity and diffusion limitation could account for the reversal in sign and exaggeration of the slopes. To further investigate this problem we explicitly measured PECO2 vs. exhaled volume in two additional experiments and compared these findings to 40 previously studied animals.

Recent anecdotal reports that some synchronized swimmers have become dizzy or disorientated towards the end of their performance, and in the worst cases fainted underwater, have caused concern. However, the rules of synchronized swimming encourage slow performance of compulsory figures, and an analysis of the competition placings and duration of underwater sequences showed that the highest rankings were gained by slowly performed compulsory figures and free programmes containing a long underwater sequence. The combination of breath-holding and the vigorous exercise involved suggests that some of the symptoms complained of by the swimmers might be due to hypoxia. We therefore studied the alveolar gas tensions in nine members of the Great Britain National Squad immediately following the performance of set figures and the initial underwater sequence of their free routine in a swimming-bath. All were cyanosed after the underwater sequences of the free routine and reported being mildly confused. The mean(s.d.) alveolar PO2 at this stage was 5.07(1.1) KPa, while three girls had an alveolar PO2 below 4 KPa, the lowest being 3.67 KPa. These gas tensions suggest that potentially dangerous levels of hypoxia may develop during competitive synchronized swimming and that prolonged underwent sequences should not be encouraged.

During inhalation anaesthesia the breathing system serves to control the composition of the alveolar gas mixture. As shown in Fig. 1, the breathing system has a crucially important place in a very complex system composed of many subsystems. The breathing system is the interface between the patient and the anaesthesia system, and therefore it should be properly designed and adequately monitored.

A triaxial alveolar gas diagram to depict fractional concentration of oxygen, carbon dioxide and nitrogen is described, in which the R = 1 line is always implicit. Although it is not claimed that this representation leads to new insights into respiratory physiology, a method of plotting on a triaxial coordinate system has been found to be well suited to many applications when a direct display of fractional nitrogen concentration is required.

Heart rate, alveolar gas partial pressures and blood lactate (BLa) concentration were measured during synchronized swimming in six subjects. During upside-down breath-holding lasting 50 s, heart rate fell progressively from 98 +/- 14 to 70 +/- 7 beats min-1 (mean +/- S.D.). While breath-holding during the compulsory figures, the subjects' heart rate increased to 142 +/- 5 beats min-1 and then fell to 72 +/- 10 beats min-1. At the end of breath-holding, alveolar oxygen pressure had fallen significantly (60 mmHg), whereas alveolar carbon dioxide pressure showed only minor changes (48 mmHg). The increase in BLa concentration due to the execution of compulsory figures was approximately 1 mM; in the free routines, BLa concentration increased by 3.4 +/- 0.5 mM. The net energy cost of completing a compulsory figures lasting 45 s was 34.6 kJ.

A cardinal feature of the human lung is that alveolar gas and blood are separated by an extremely thin membrane. This is essential because the respiratory gases pass through it by passive diffusion, and the diffusion resistance is proportional to the thickness of the membrane. However despite the extreme thinness of the blood-gas barrier, maintenance of its integrity is essential for efficient gas exchange. Mechanical failure will cause alveolar edema or even frank alveolar hemorrhage. We, therefore, decided to investigate the strength of the blood-gas barrier by raising the pressure inside pulmonary capillaries and looking for evidence of ultrastructural changes in their walls.

Short-term intraindividual variability of the parameters derived from respiratory transfer impedance (Ztr) measured from 4 to 32 Hz was studied in 10 healthy subjects. The corresponding 95% confidence intervals (CIo) were compared with those computed from a single set of data (CIL) according to Lutchen and Jackson (J. Appl. Physiol. 62: 403-413, 1987). Ztr was analyzed with the six-coefficient model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), which includes airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility (Cg). The lowest variability was seen for Iaw (CIo = 11.1%), closely followed by Raw (14.3%) and Cti (14.8%), and the largest for Rti and Iti (24.6 and 93.6%, respectively). Using a simpler model, where Iti was excluded, significantly decreased the variability of Iaw (P less than 0.01) and Rti (P less than 0.05) but was responsible for a systematic decrease of Raw and Iaw and increase of Rti. Except for Raw with both models and Iaw with the simpler model, CIL was greater than CIo. Whatever the model, a high correlation between both sets of confidence intervals was found for Rti and Iaw, whereas no correlation was seen for Raw. This suggests that the variability of the former coefficients mainly reflects experimental noise, whereas that of the latter is largely due to biological variability.

It is well known that in chronic pulmonary hyperinflation defects in intrapulmo-nary gas mixing and in V/Q ratio are likely to occur.

Most commonly used pulmonary function tests require patients to perform some sort of gymnastic respiratory maneuver such as a forced expiration. These tests are therefore restricted to conscious, cooperative adult humans. Measurements of mechanical, or input acoustic impedance of the respiratory system (Zin) can be made in animals, non-cooperative adults and children, and infants. The first measurements of Zin, made in normal human subjects were reported by Dubois et al. in 1956 [3]. There were certain characteristics of Zin that suggested that the normal respiratory system behaved as though all of the alveoli could be lumped into a single compartment. The single compartment model that they proposed consisted of 6-elements and is illustrated in Fig. 1. If this were the appropriate model and if we could make Zin measurements over the appropriate frequency range, there is the potential of estimates of at least two parameters that are of clinical importance, airway resistance (Raw) and thoracic gas volume which is directly related to alveolar gas compression compliance (Cg). At about the same time that DuBois’ work was published, Otis et al. [18] reported that Zin in patients with diseases of the lung did not behave like a single compartment system. Specifically, they found that the effective compliance of the system was frequency dependent. This implies that there would also be a frequency dependent drop in the real part of Zin (Re) for low frequencies; a characteristic not found in normals and one that is not consistent with the 6-element model. Otis et al. suggested that these phenomena were due to inhomogeneities in the parallel airway/tissue pathways.

Sildenafil Improves Exercise Peak Oxygen Consumption and Ventilation Efficiency by a Synergistic Effect on Endothelial Function and Alveolar Gas Diffusion in Heart Failure Patients Marco Guazzi, Paola Satariano, Fabio Di Marco, Cesare Fiorentini, Gabriele Tumminello1—Department of Cardiology, University of Milano, San Paolo Hospital, Milano, Italy; Respiratory Unit, San Paolo Hospital, Milano, Italy

Accessible online at: www.karger.com/journals/res Many doctors think God erred when he made airway muscles but others, including David Blyth who writes in this issue of Respiration [1], believe airway muscles normally provide more benefit than harm. Studies on the lungs of marine mammals support the latter view, because their airways are reinforced with cartilage and muscle all the way to the alveoli. The puzzle is this: in marine mammals the muscles appear to keep the airway open but, in terrestrial mammals, Dr. Blyth argues their beneficial role is to constrict. Could both statements be true? In terrestrial mammals, including shallow divers such as beavers, otters and hippopotami, the airways are floppier than the alveoli they serve and so collapse before the alveoli are empty [2, 3]. Hence our residual volumes exist and increase as airways are weakened by age or disease. Dr. Blyth in his clear and enjoyable paper claims that the normal, i.e. appropriate, functions of airway muscle are to narrow the airways and so facilitate the expulsion of unwanted material, and to shorten the tracheo-bronchial tree, aiding expiration. Marine mammals come from very diverse evolutionary roots but all have airways that are stronger than the alveoli they serve, ensuring complete alveolar collapse as they dive below a depth of 30 m or so. This shunts alveolar gas away from pulmonary capillary blood, neatly avoiding the risks of nitrogen narcosis, oxygen toxicity and decompression illness, that plague man, the only deep-diving terrestrial mammal. It is possible that both views of appropriate functions are true. Think of the muscles as a cylindrical geodetic mesh, as if designed by Buckminster Fuller. When shortening of the cylinder is opposed the mesh would contract isometrically, strengthening the walls. When shortening of the cylinder is permitted the mesh contracts isotonically, constricting the walls. It is possible that both functions are appropriate and could even be exercised sequentially in a single breath. It is certain that some aspects of airway function are inappropriate in asthma. It may also turn out that the temporally and spatially blunderbuss methods used to study airway muscle function in asthma are inappropriate to the examination of the normal functions Dr. Blyth has elegantly brought to mind.

The frequency dependence of effective compliance, Ceff, and resistance, Reff, are reproduced by means of a two- or four-compartment linear mathematical model with pleural pressure as a sinusoidal input. The model simulates the mechanical properties of lung parenchyma, alveolar gas, bronchial wall, and cheeks, as well as the distribution of gaseous resistances and inertances within the airways. Values, representative for a young healthy adult, are assigned to these various parametersmit appears from this study: 1) that the gas inertance produces a very marked increase of Ceff, noticeable already below 1 cycle/smto obtain a frequency independence of Ceff between 0 and 2 cycles/s, it is necessary to introduce a marked inhomogeneity in the model. 2) Such an inhomogeneity is realized by simulating a pleural pressure difference of 6 cmH2O between the compartments of the bialveolar model. It can be shown that this corresponds to a total pleural pressure difference of about 9 cmH2O in a model consisting of an infinite number of compartments. 3) The influence of the compressibility of alveolar gas and of mechanical properties of the bronchial wall and of the cheeks on Ceff and Reff is small or negligible.

In supplement to a previous study ( Respir. Physiol. 46: 193–201, 1981) further relationships are presented that are particularly suited for comaparing the extent of diffusion and perfusion limitation in alveolar gas transfer.

Our measurements on cat's lung show that pulmonary veins and venules are not collapsible, but remain open when the alveolar gas pressure (PA) exceeds the local blood pressure (Pv). Their compliance constants show no discontinuity as Pv falls below PA. The capillaries, however, do collapse when PA greater than Pv. The explanation of the patency of the veins when PA greater than Pv is the pulling on the blood vessels by tension in the interalveolar septa. Photomicrographs show that each venule (or vein) is pulled radially by three or more interalveolar septa. Capillary sheets, however, are exposed to gas on the lateral sides and can readily collapse when PA greater than Pv. These facts provide the key to the analysis of pulmonary blood flow in zone 2. The “sluicing” gate, i.e., the site of flow limitation, must be located at the junctions of capillary sheets and the first generation of venules. Further, data on the branching pattern and compliance of small pulmonary veins, which are needed in quantitative analysis of pulmonary circulation, are presented.