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Paratuberculosis is an important disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Early detection is crucial for successful infection control, but available diagnostic tests are still dissatisfying. Methods allowing a rapid, economic, and reliable identification of animals or herds affected by MAP are urgently required. This explorative study evaluated the potential of volatile organic compounds (VOCs) to discriminate between cattle with and without MAP infections. Headspaces above fecal samples and alveolar fractions of exhaled breath of 77 cows from eight farms with defined MAP status were analyzed in addition to stable air samples. VOCs were identified by GC–MS and quantified against reference substances. To discriminate MAP-positive from MAP-negative samples, VOC feature selection and random forest classification were performed. Classification models, generated for each biological specimen, were evaluated using repeated cross-validation. The robustness of the results was tested by predicting samples of two different sampling days. For MAP classification, the different biological matrices emitted diagnostically relevant VOCs of a unique but partly overlapping pattern (fecal headspace: 19, alveolar gas: 11, stable air: 4–5). Chemically, relevant compounds belonged to hydrocarbons, ketones, alcohols, furans, and aldehydes. Comparing the different biological specimens, VOC analysis in fecal headspace proved to be most reproducible, discriminatory, and highly predictive.

New findings What is the central question of this study? We modelled the alveolar pathway during breath holding on the hypothesis that it follows a hypoventilation loop on the O2 -CO2 diagram. What is the main finding and its importance? Validation of the model was possible within the range of alveolar gas compositions compatible with consciousness. Within this range, the experimental data were compatible with the proposed model. The model and its characteristics might allow predictions of alveolar gas composition whenever the alveolar ventilation goes to zero; for example, static and dynamic breath holding at the surface or during ventilation/intubation failure in anaesthesia. Abstract According to the hypothesis that alveolar partial pressures of O2 and CO2 during breath holding (BH) should vary following a hypoventilation loop, we modelled the alveolar gas pathways during BH on the O2 -CO2 diagram and tested it experimentally during ambient air and pure oxygen breathing. In air, the model was constructed using the inspired and alveolar partial pressures of O2 ( P I O 2 and P A O 2 , respectively) and CO2 ( P IC O 2 and P AC O 2 , respectively) and the steady-state values of the pre-BH respiratory exchange ratio (RER). In pure oxygen, the model respected the constraint of P AC O 2 = - P A O 2 + P I O 2 . To test this, 12 subjects performed several BHs of increasing duration and one maximal BH at rest and during exercise (30 W cycling supine), while breathing air or pure oxygen. We measured gas flows, P A O 2 and P AC O 2 before and at the end of all BHs. Measured data were fitted through the model. In air, P I O 2 = 150 ± 1 mmHg and P IC O 2 = 0.3 ± 0.0 mmHg, both at rest and at 30 W. Before BH, steady-state RER was 0.83 ± 0.16 at rest and 0.77 ± 0.14 at 30 W; P A O 2 = 107 ± 7 mmHg at rest and 102 ± 8 mmHg at 30 W; and P AC O 2 = 36 ± 4 mmHg at rest and 38 ± 3 mmHg at 30 W. By model fitting, we computed the RER during the early phase of BH: 0.10 [95% confidence interval (95% CI) = 0.08-0.12] at rest and 0.13 (95% CI = 0.11-0.15) at 30 W. In oxygen, model fitting provided P I O 2 : 692 (95% CI = 688-696) mmHg at rest and 693 (95% CI = 689-698) mmHg at 30 W. The experimental data are compatible with the proposed model, within its physiological range.

Although determination of ventilation–perfusion (VA/Q) distribution and/or simultaneous determination of VA/Q and diffusing capacity–perfusion (D/Q) distribution are needed to precisely diagnose gas exchange abnormalities occurring in the lung periphery, these analyses cannot be straightforwardly performed in clinical situation. On the other hand, effective alveolar–arterial PO2 difference (effective AaDO2) and physiological dead space (VD/VT), both of which are appraised as a base of the classical gas exchange theory, can be measured with ease. In classical gas exchange theory, effective alveolar gas compositions (effective PAO2 and PACO2), effective AaDO2, and physiological VD/VT are clinically important while diagnosing gas exchange abnormalities concerning O2 and CO2 in a first approximation. Key assumption allowing classical gas exchange theory to be applied for clinical practice is that effective PACO2 can be replaced with arterial PCO2 (PaCO2) that is measured routinely at bedside. If this assumption is not adopted, measurements of PO2 and PCO2 in mixed venous blood, which are only possible through right heart catheterization, are indispensable for determining representatives of PAO2 and PACO2. When effective PACO2 (= PaCO2) is known, other indicators, including effective PAO2, effective AaDO2, and physiological VD/VT, can be easily decided. Effective AaDO2 functions as the indicator for identifying regions with low VA/Q values, including right-to-left shunt (VA/Q = zero), while physiological VD/VT is useful for detecting regions with high VA/Q values, including alveolar dead space (VA/Q = infinite).

Four normal subjects used a partial rebreathing procedure to deliver frequent alveolar gas samples during breath holding with air. In breath holding during mild exertion, O2 uptake declined steadily while CO2 transfer dropped abruptly and later ceased entirely as alveolar Pco2 reached a virtual plateau. Application of estimated instantaneous values of R provided an indication of mixed venous blood values and permitted interpretation in terms of the changing venous-alveolar-arterial relationships. Arterial Pco2 very early equaled mixed venous Pco2 and then exceeded it increasingly. The plateau of alveolar Pco2 was due in part to the fall in alveolar Po2 since decreasing O2 uptake lessened the CO2-concentrating effect of lung-volume reduction while the Pco2-elevating effect of blood oxygenation was also diminishing. However, an important slowing of the rise in mixed venous CO2 content and Pco2 was also noted and remains unexplained. Submitted on October 17, 1962

Capture of CO and NO by blood requires molecules to travel by diffusion from alveolar gas to haemoglobin molecules inside RBCs and then to react. One can attach to these processes two times, a time for diffusion and a time for reaction. This reaction time is known from chemical kinetics and, therefore, constitutes a unique physical clock. This paper presents a time-based bottom-up theory that yields a simple expression for DLCO and DLNO that produces quantitative predictions which compare successfully with experiments. Specifically, when this new approach is applied to DLCO experiments, it can be used to determine the value of the characteristic diffusion time, and the value of capillary volume (Vc). The new theory also provides a simple explanation for still unexplained correlations such as the observed proportionality between the so-called membrane conductance DM and Vc of Roughton and Forster’s interpretation. This new theory indicates that DLCO should be proportional to the haematocrit as found in several experiments.

In this paper, we model breathing at the level of a human alveolus by developing a novel mathematical framework that links pulmonary mechanics and gas exchange. Unlike previous models, the developed alveolar model comprises the alveolar gas mixture, capillaries perfused in the alveolar wall, pulmonary surfactant lining the alveolus and the pleural cavity. The inclusion of the multiple compartments affords interested researchers the chance to study the effect of several respiratory factors on breathing. Here, we investigate the effect of holding breath, breathing at different altitudes and frequencies, and varying cardiac output. The important role of pulmonary surfactant in breathing is also highlighted. In addition, we propose a new method to model the transport of oxygen and carbon dioxide between the alveolus and perfused capillaries, and provide a Lagrangian description of surfactant dynamics. Finally, the mechanical work of breathing at the level of the alveolus is derived and implemented to compare the required breathing effort in different scenarios. Numerical results are consistent with published experimental and computational work.

The pros and cons of different algorithms developed for estimating breath-by-breath (B-by-B) alveolar O2 transfer (\( {\dot{\text{V}}} \)O2A) will be detailed and discussed. \( {\dot{\text{V}}} \)O2,A is the difference between O2 uptake at the mouth and changes in alveolar O2 stores (∆VO2,si), which, for any given breath, are equal to the alveolar volume change at constant \( {\text{F}}_{{{\rm AO}_{2} }} \left[ {\left( {{\text{F}}_{{{\rm A}i{\text{O}}_{2} }} \times \, \Delta {\text{V}}_{{{\rm A}i}} } \right)} \right] \) plus the O2 alveolar fraction change at constant alveola volume \( [{\text{V}}_{{{\rm A}i - 1}} \times \left( {{\rm F}_{{{\text{A}}i}} {-}{\rm F}_{{{\text{A}}i - 1}} } \right)_{{{\text{O}}_{2} }} ] \), where VAi−1 is the alveolar volume at the beginning of a breath. Therefore, \( {\dot{\text{V}}} \)O2,A can be determined B-by-B if VAi−1 is: (i) set equal to the subject’s FRC (algorithm of Auchincloss, A) or to zero; (ii) measured (optoelectronic plethysmography, OEP); (iii) selected according to a procedure that minimises B-by-B variability (algorithm of Busso and Robbins, BR). Alternatively, the respiratory cycle can be redefined as the time between equal FO2 in two subsequent breaths (algorithm of Gronlund, G), making any assumption of VAi−1 unnecessary. All the above methods allow an unbiased estimate of \( {\dot{\text{V}}} \)O2,A at steady state, albeit with different precision. However, the algorithms “per se” affect the parameters describing the B-by-B kinetics during exercise transitions. Among these approaches, BR and G, by increasing the signal to noise ratio of the measurements, reduce the number of exercise repetitions necessary to study \( {\dot{\text{V}}} \)O2,A kinetics, compared to A approach. OEP and G (though technically challenging and conceptually still debated), thanks to their ability to track ∆VO2s changes during the early phase of exercise transitions, appear rather promising for investigating B-by-B gas exchange.

To check whether the evolution of alveolar pressures of O2 (PAO2) and CO2 (PACO2) explains the cardiovascular responses to apnoea, eight divers performed resting apnoeas of increasing duration in air and in O2. We measured heart rate (fH), arterial pressure (AP), and peripheral resistances (TPR) beat-by-beat, PAO2 and PACO2 at the end of each apnoea. The three phases of the cardiovascular response to apnoea were observed. In O2, TPR increase (9 ± 4 mmHg min l−1) and fH decrease (-11 ± 8 bpm) were lower than in air (15 ± 5 mmHg min l−1 and -28 ± 13 bpm, respectively). At end of maximal apnoeas in air, PAO2 and PACO2 were 50 ± 9 and 48 ± 5 mmHg, respectively; corresponding values in O2 were 653 ± 8 mmHg and 55 ± 5 mmHg. At end of phase II, PAO2 and PACO2 in air were 90 ± 13 mmHg and 42 ± 4 mmHg respectively; corresponding values in O2 were 669 ± 7 mmHg and 47 ± 6 mmHg. The PACO2 increase may trigger the AP rise in phase III.

Measurement of the gas exchange efficiency of the lung is often required in the practice of pulmonary medicine and in other settings. The traditional standard is the values of the PO2, PCO2, and pH of arterial blood. However arterial puncture requires technical expertise, is invasive, uncomfortable for the patient, and expensive. Here we describe how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency. The new procedure is noninvasive, well tolerated by the patient, and takes only a few minutes. It could be particularly useful when repeated measurements of pulmonary gas exchange are required. One product of the procedure is the difference between the PO2 of end-tidal alveolar gas and the calculated PO2 of arterial blood. This measurement is related to the classical alveolar-arterial PO2 difference based on ideal alveolar gas. However that traditional index is heavily influenced by lung units with low ventilation-perfusion ratios, whereas the new index has a broader physiological basis because it includes contributions from the whole lung.

Alveolar recruitment maneuvers in the control of lung atelectasis ABSTRACT: The partial or total collapse of the lung or a lung lobe called atelectasis is one of the major complications of patients assisted with mechanical ventilation in the intensive care unit and in the peri-operative period. The main factors which come into atelectasis in alveoli are: pulmonary tissue compression, alveolar gas absorption, and loss of alveolar surfactant function. To counteract atelectasis, several maneuvers for alveolar recruitment are used which aim to reopen

Introduction We tested the hypothesis that the alveolar gas composition at the transition between the steady phase II (φ2) and the dynamic phase III (φ3) of the cardiovascular response to apnoea may lay on the physiological breaking point curve (Lin et al., 1974). Methods Twelve elite divers performed maximal and φ2-interrupted apnoeas, in air and pure oxygen. We recorded beat-by-beat arterial blood pressure and heart rate; we measured alveolar oxygen and carbon dioxide pressures (P A O 2 and P A CO 2 , respectively) before and after apnoeas; we calculated the P A CO 2 difference between the end and the beginning of apnoeas (ΔP A CO 2 ). Results Cardiovascular responses to apnoea were similar compared to previous studies. P A O 2 and P A CO 2 at the end of φ2-interrupted apnoeas, corresponded to those reported at the physiological breaking point . For maximal apnoeas, P A CO 2 was less than reported by Lin et al. (1974). ΔP A CO 2 was higher in oxygen than in air. Conclusions The transition between φ2 and φ3 corresponds indeed to the physiological breaking point . We attribute this transition to ΔP A CO 2 , rather than the absolute P A CO 2 values, both in air and oxygen apnoeas.

After Rahn and Fenn published A Graphical Analysis of the Respiratory Gas Exchange in 1955, understanding of the importance of ventilation-perfusion matching to pulmonary gas exchange grew rapidly. Rahn and Fenn highlighted that alveolar gas concentrations were intimately related to the associated ventilation-perfusion (\( {\dot{V}}_A/\dot{Q} \)) ratio. Riley and Cournand expanded this into the three-compartment lung model with shunt, ideal, and deadspace compartments. This early work was important since the multiple inert gas technique (MIGET) uses the same principles of mass conservation. MIGET also built on the work of Kety, who showed that the fractional retention of an inert gas in arterial blood was function of solubility and \( {\dot{V}}_A/\dot{Q} \) ratio. Later, Farhi and Yokoyama devised a method for measuring retention of inert gases during washout, from which a two-compartment model of \( {\dot{V}}_A/\dot{Q} \) inequality was derived. Lenfant and Okubo exploited the fact that arterial partial pressure of oxygen (\( {P}_{{\mathrm{O}}_2} \)) response to inspired O2 depended on the \( {\dot{V}}_A/\dot{Q} \) ratio and modeled a continuous distribution of \( {\dot{V}}_A/\dot{Q} \) ratios to compute the underlying \( {\dot{V}}_A/\dot{Q} \) ratios explaining the response. Using computer algorithms to solve the gas exchange equations of these pioneering investigators and to quantify the O2 and CO2 dissociation curves, Kelman, Olszowka, and West studied complex gas exchange behavior by taking theoretical \( {\dot{V}}_A/\dot{Q} \) distributions and evaluating the effect on O2 and CO2 exchange. Wagner and West working with Saltzman realized that by using the inert gas approach of Farhi and Yokoyama, and measuring the elimination, simultaneously, of several inert gases of widely varying solubility, continuous distributions of \( {\dot{V}}_A/\dot{Q} \) could be measured. This is what gave rise to the multiple inert gas elimination technique.

Capnography, the non-invasive monitoring of the CO2 partial pressure in the exhaled gas provides information on lung ventilation and perfusion. The reference mainstream (MS) method measures CO2 directly at the airway opening. Sidestream (SS) devices analyse a gas sample aspirated through a tube, distorting the capnogram in an unclarified manner and degree. We investigated the influence of sampling rate on the shape factors of the SS capnogram. Measurements were made simultaneously with MS and SS capnographs, the latter being equipped with adjustable sampling flow in 6 anaesthetised, ventilated patients. Phase 2 and 3 slopes (S2 and S3) were derived from time capnograms. S2 describes the transition between the emptying of bronchial and alveolar gas, S3 reflects the heterogeneity of alveolar ventilation. To assess the effects of sampling flow on capnogram shape, we analysed correlations between the sampling flow and the difference of SS and MS parameters (S2diff, S3diff). By increasing sampling flow from 100 to 400 ml/min in 3 steps, S2diff exhibited monotonous, linear decrease (R2=0.47, p Our results highlight that changes in sampling flow rate bias the shape factors derived from SS capnogram. Increasing the sampling flow from 200 to 400-500 ml/min improves the accuracy of SS capnographic parameter estimations, approaching those obtained by the MS method. In clinical practice, however, the feasibility of increasing the sampling flow is limited by the loss of tidal volume, which is of great importance in paediatric patients. Supported by OTKA grant K115253.

MRI of hyperpolarized (129)Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T2* and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo-time sequence was introduced, and its feasibility to quantitatively assess emphysema-like pulmonary tissue destruction by a combination of dissolved- and gas-phase (129)Xe lung MRI was investigated. The ultrashort echo-time has made it possible to acquire dissolved (129)Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm(2) and to obtain T2* of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of (129)Xe magnetization that diffused into the septa relative to the gas-phase magnetization F was regionally evaluated. The mean F value of elastase-treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface-to-volume ratio.

The single-breath carbon monoxide diffusing capacity (DL(CO)) is the product of two measurements during breath holding at full inflation: (1) the rate constant for carbon monoxide uptake from alveolar gas (kco [minute(-1)]) and (2) the "accessible" alveolar volume (Va). kco expressed per mm Hg alveolar dry gas pressure (Pb*) as kco/Pb*, and then multiplied by Va, equals Dl(CO); thus, Dl(CO) divided by Va (DL(CO)/Va, also called Kco) is only kco/Pb* in different units, remaining, essentially, a rate constant. The notion that DL(CO)/Va "corrects" DL(CO) for reduced Va is physiologically incorrect, because DL(CO)/Va is not constant as Va changes; thus, the term Kco reflects the physiology more appropriately. Crucially, the same DL(CO) may occur with various combinations of Kco and Va, each suggesting different pathologies. Decreased Kco occurs in alveolar-capillary damage, microvascular pathology, or anemia. Increased Kco occurs with (1) failure to expand normal lungs to predicted full inflation (extrapulmonary restriction); or (2) increased capillary volume and flow, either globally (left-to-right intracardiac shunting) or from flow and volume diversion from lost or damaged units to surviving normal units (e.g., pneumonectomy). Decreased Va occurs in (1) reduced alveolar expansion, (2) alveolar damage or loss, or (3) maldistribution of inspired gases with airflow obstruction. Kco will be greater than 120% predicted in case 1, 100-120% in case 2, and 40-120% in case 3, depending on pathology. Kco and Va values should be available to clinicians, as fundamental to understanding the clinical implications of DL(CO). The diffusing capacity for nitric oxide (DL(NO)), and the DL(NO)/DL(CO) ratio, provide additional insights.

2011 marks the 100th anniversary of one of the most important early research expeditions to high altitude. The principal participants were J.S. Haldane and C.G. Douglas from Oxford, Y. Henderson from Yale, and E.C. Schneider from Colorado College. Pikes Peak just outside Colorado Springs proved to be an excellent venue because of its substantial altitude of 4300 m, convenient access via a cog railway, and comfortable living accommodation. The expedition had a classical design with measurements made first at sea level, then on the summit for five weeks, and then at sea level again. The extensive scientific program included descriptions of acute mountain sickness, many measurements of partial pressures in alveolar gas and arterial blood, changes in ventilation including periodic breathing, exercise measurements, and a large number of blood studies. One error was the conclusion that the arterial PO2 could considerably exceed the alveolar value implying oxygen secretion by the lung, but this should not detract from the other important advances. Mabel FitzGerald was invited to be a member of the expedition but did not join the men on the summit. Instead she visited various mining camps in Colorado at somewhat lower altitudes and carried out classical studies of alveolar gas partial pressures and hemoglobin values. Indeed her results of alveolar PO2 and PCO2 are frequently cited today. The Pikes Peak expedition was a model and it had an extensive influence on later studies.

This chapter will discuss the transport of carbon monoxide (CO) from the environment to the tissues of the body and physiological effects on blood-borne cells and perivascular tissues. It will review the physiology of CO exchange between alveolar gas and pulmonary capillary blood, dynamics of hemoglobin transport, the effects of CO on blood elements, and the effects of CO on extravascular tissues at the capillary bed. Effects of CO from exogenous and endogenous sources on the activities of different proteins will be reviewed. Because CO binds competitively to heme-containing proteins its effects depend on CO concentration relative to alternative ligands. Therefore, some discussion is devoted to how nitric oxide and hydrogen sulfide influence CO effects.

Increased end-tidal oxygen (ET-O(2)) and decreased end-tidal carbon dioxide (ET-CO(2)) gas tensions are noninvasively measurable correlates of ventilatory inefficiency, leading to increased ventilatory requirements relative to gas exchange among patients with chronic heart failure (CHF). We investigated the prognostic value of ET-O(2) and ET-CO(2) as predictors of CHF mortality.We measured resting ET-O(2) and ET-CO(2) electrochemically in 134 patients with symptomatic CHF in the supine position. We used Kaplan-Meier analysis, Cox proportional hazard models, and receiver operating characteristic curves to test our hypothesis.At a median follow-up of 16.5 months, 32 patients had died. ET-O(2) levels were increased (P = .001) and ET-CO(2) levels decreased (P = .002) with increased New York Heart Association class (I-IV). Survivors showed lower ET-O(2) (121 vs 118 mm Hg; P = .021) and higher ET-CO(2) (33.2 vs 32.1 mm Hg; P = .032) levels than nonsurvivors. Patients with ET-O(2) values ≥121 mm Hg and/or ET-CO(2) values31 mm Hg had an increased risk of death with hazard ratios of 2.93 (95% confidence interval [CI], 1.43-6.01) and 2.47 (95% CI, 1.23-4.97), respectively. Kaplan-Meier estimates for follow-up mortality with ET-O(2) ≥121 mm Hg and/or ET-CO(2)31 mm Hg were 83.8% (vs 60.1%; P = .0014) and 80.3% (vs 60.2%; P = .0061), respectively. Areas under the receiver operating characteristic curves for prediction of death with ET-O(2) and ET-CO(2) were both significant and similar to that of echocardiographic left ventricular function.In CHF, high levels of ET-O(2) and low levels of ET-CO(2) are associated with increased mortality. We suggest that the measurements may be useful prognostic markers for risk stratification.

The primary objective of the American Medical Research Expedition to Everest was to obtain information on human physiology at the highest possible altitude, including the Everest summit. An important data point was the barometric pressure on the summit, because this determines the inspired P(O(2)). The first measurement ever taken was 253.0 mmHg. Because modeling studies had shown that extreme hyperventilation was essential to reach these great altitudes, 34 alveolar gas samples were collected above an altitude of 8000 m, including 4 on the summit. These showed that hyperventilation reduced the alveolar P(CO(2)) to between 7 and 8 mmHg in one climber. An important finding was that alveolar P(O(2)) was defended at a value of about 35 mmHg by the increasing hyperventilation as the climbers ascended higher. Venous blood samples collected on two summiters gave a mean base excess of -7.2 meq.L(-1). Using the alveolar P(CO(2)) value, this gave an arterial pH of over 7.7, indicating an extreme degree of respiratory alkalosis. While climbing at an altitude of 8300 m, one summiter showed a respiratory frequency of 86 breaths.min(-1) and tidal volume of 1.26 L, indicating very rapid shallow breathing. Maximal oxygen consumption for the summit was derived by having well-acclimatized subjects exercise maximally at an altitude of 6300 m while breathing 14% oxygen. The V(O(2)) was just over 1 L.min(-1), which is sufficient to explain how exceptional humans can reach the summit without supplementary oxygen. In addition to the measurements at altitudes over 8000 m, data were obtained at two camps at 5400- and 6300-m altitude. These gave information on the control of ventilation, periodic breathing, blood physiology, cerebral function, and metabolism.

When Edmund Hillary and Tenzing Norgay reached the summit of Mt. Everest in 1953, it was the culmination of many attempts beginning in 1921. Alexander Kellas had actually predicted as early as 1920 that the mountain could be climbed, but the extreme altitude of 8848 m with the consequent oxygen deprivation had foiled previous attempts. One reason for the success of the 1953 expedition was the work done by the British physiologist Griffith Pugh in 1952 when he studied many of the physiological factors at high altitude including the oxygen requirements. Seven years later, Pugh and Hillary teamed up again for the Silver Hut Expedition in 1960–1961 that elucidated many of the problems of very high altitude. A group of physiologists spent several months at an altitude of 5800 m in a prefabricated hut and studied many aspects of exercise, pulmonary gas exchange, control of ventilation, and blood changes. Maximal exercise was measured as high as 7440 m and raised anew the question of whether Everest could ever be climbed without supplementary oxygen. The answer was shown to be yes in 1978 by Messner and Habeler, and 3 years later the American Medical Research Expedition to Everest clarified the physiological adaptations that allow humans to reach the highest point on earth. Five people reached the summit, the barometric pressure there was measured for the first time, and alveolar gas samples from the summit showed the critical importance of the extreme hyperventilation. However, the maximal oxygen consumption for the summit inspired PO2 of 43 mmHg was shown to be only about 1 l min−1. In other words, the highest point on earth is very close to the limit of human tolerance to oxygen deprivation. As we celebrate the anniversary of Charles Darwin, it would be nice to have an evolutionary explanation for this, but in fact it is a cosmic coincidence.

We determined the oxygen isotope fractionation degree for oxygen utilized (delta(U)) in expired alveolar gas relative to inspired air in patients with chronic obstructive lung disease (COPD) and, for comparison, in two groups of healthy subjects, old and young. In addition, we determined Delta(rel)R(vent) and Delta(rel)R(tot). These determinants of delta(U) (=Delta(rel)R(tot)-Delta(rel)R(vent)) are related to the oxygen isotope fractionation which occurs in the first part of the O(2) pathway by ventilation of alveolar gas (Delta(rel)R(vent)) and by O(2) transport and utilization in the rest of the O(2) pathway from the alveolar space (Delta(rel)R(tot)). Mean delta(U) values for the three groups of subjects were close: 9.0, 9.0 and 9.9 per thousand, respectively, with no significant differences between groups. Mean Delta(rel)R(vent) for patients with COPD was substantially larger than for young, healthy subjects, 4.0 per thousand versus 0.94 per thousand, with P10(-3). This result indicates that the contribution of intrapulmonary gas transport by diffusion to Delta(rel)R(vent) is larger for patients with COPD than for young, healthy subjects. Mean Delta(rel)R(tot) for patients with COPD was also larger than for young, healthy subjects, 13.0 per thousand versus 10.84 per thousand, but this difference was not significant (P=0.06). Further, Delta(rel)R(tot) was much larger than Delta(rel)R(vent) for all groups of subjects (P10(-7)).

The aim of this study is to propose a new approach to estimate non-invasively arterial carbon dioxide partial pressure ( P a C O 2 ) . This approach was based on the reconstruction of alveolar gas composition over each breath from a tidally ventilated lung model ( P M C O 2 ) . Eight healthy young subjects were studied during a ramp exercise test on a cycle ergometer. Arterial samples were drawn at rest and every minute during the exercise test for determination of P a C O 2 . P a C O 2 was compared with indirect estimates of P C O 2 : P M C O 2 , end-tidal P C O 2 ( P E T C O 2 ) and an empirical equation involving P E T C O 2 and tidal volume ( P J C O 2 ) . The difference between estimated and measured P a C O 2 on the whole ramp exercise was −0.3 ± 1.9 mmHg for P M C O 2 , 1.0 ± 2.2 mmHg for P E T C O 2 and −1.7 ± 1.7 mmHg for P J C O 2 . P E T C O 2 and P J C O 2 were significantly different from actual P a C O 2 ( P P a C O 2 than the two other indirect methods during ramp exercise.

Respiratory mass spectrometers involve electron bombardment ion sources and for mass separation magnetic sector fields or flight time measurement. The ions are detected by DC amplifiers. The inlet system should have the same conductivity for gases and vapors or eliminate changes in water vapor concentration. The different stable O2 isotopes can be measured with sufficient sensitivity to show their different exchange between alveolar gas and blood. The interpretation of mass spectra or mono isotopic analyses has to take into account possible interferences between different ions of the same mass.

Background: A crucial issue in the analysis of exhaled breath is the collection of gaseous samples. The analysis of pure alveolar gas is the method of choice if contamination of samples is to be minimized. Monitoring of expired CO_{2} can be used to identify alveolar gas. The purpose of this study was to evaluate a bed side version of this technique using visual CO_{2} control by means of a capnometer. Methods: 22 mechanically ventilated patients of an ICU were enrolled into the study. Alveolar and mixed expiratory gas, and arterial blood were sampled. PCO_{2} in blood and gas was determined in a blood gas analyzer. End tidal PCO_{2} was monitored in all patients by a fast responding main stream capnometry. Taking the gaseous samples was visually synchronized with the expired CO_{2}. Results: Alveolar CO_{2} contents measured during two different respiratory cycles were identical (p 0.86). The variation of the CO_{2} content during 10 measurements in one patient was lower than 4%. Arterial PCO_{2}, PCO_2 in alveolar gas and end tidal PCO_{2} showed positive correlation. Conclusions: The visually CO_{2}-controlled sampling technique of alveolar gas is a reliable and reproducible method. It represents an important step in simplifying and standardizing breath analysis.

Equations governing oxygen transport from alveolar gas to red blood cells flowing through pulmonary capillaries are written down. Some analytical predictions are made on factors affecting the rate at which this process takes place. Numerical simulations are carried out to investigate the effect of red blood cell shape, capillary dimensions, haematocrit and choice of oxygen dissociation curve on pulmonary oxygen transport. These factors all have an effect on pulmonary transport, with the effect being much more marked for simulations with low oxygen levels, typical of those seen in some subjects with respiratory disease.

Background Analyzing propofol concentration in expired alveolar gas (cPA) may be considered as a convenient, noninvasive method to follow the propofol concentration in plasma (cPPL). In the current study, the authors established procedures to measure cPA and cPPL for the assessment of their relation in two animal models during anesthesia. Methods Expired alveolar gas and mixed venous and arterial blood were simultaneously sampled during continuous application of propofol for general anesthesia to three goats and three pigs. Propofol infusion rates were varied to modify plasma concentrations. cPA, sampled cumulatively over several respiratory cycles, was quantified by thermal desorption gas chromatography-mass spectrometry. cPPL was determined using reversed phase high-performance liquid chromatography with fluorescence detection. Results cPA ranged from 0 to 1.4 and from 0 to 22 parts per billion in goats and pigs, respectively, at cPPL of 0-8 microg/ml. The relation between cPA and cPPL was linear; however, the slopes of the regression lines varied between animals. Conclusion Propofol can be quantified in expired alveolar gas. The results stress the role of marked species-specific variability.

Changes in heart rate (f(H)) and cloacal ventilation frequency (f(C)) were investigated in the Fitzroy turtle, Rheodytes leukops, under normoxic (17.85 kPa) and hypoxic (3.79 kPa) conditions at 25 degrees C. Given R. leukops' high reliance on aquatic respiration via the cloacal bursae, the objective of this study was to examine the effect of varying aquatic PO(2) levels upon the expression of a bradycardia in a freely diving, bimodally respiring turtle. In normoxia, mean diving f(H) and f(C) for R. leukops remained constant with increasing submergence length, indicating that a bradycardia failed to develop during extended dives of up to 3 days. Alternatively, exposure to aquatic hypoxia resulted in the expression of a bradycardia as recorded by a decreasing mean diving f(H) with increasing dive duration. The observed bradycardia is attributed to a hypoxic-induced metabolic depression, possibly facilitated by a concurrent decrease in f(C). Results suggest that R. leukops alters its strategy from aquatic O(2) extraction via cloacal respiration in normoxia to O(2) conservation when exposed to aquatic hypoxia for the purpose of extending dive duration. Upon surfacing, a significant tachycardia was observed for R. leukops regardless of aquatic PO(2), presumably functioning to rapidly equilibrate blood and tissue gas tensions with alveolar gas to reduce surfacing duration.

Existing controversy on the effect of blood flow, and more specifically red blood cell (RBC) movement, on the alveolar gas diffusion is considered. Contrary to fundamental understanding of flow (convection) effects, there seems to be a consensus in the negligible role blood flow plays on alveolar gas transport. Notwithstanding, experimental evidence indicates an increase in the efficiency of alveolar gas exchange under high cardiac output (exercising), which could be easily explained as a result of increased blood flow. A theoretical analysis of a simplified capillary blood flow configuration, with blood considered as a homogeneous fluid (no RBCs), is presented to demonstrate the strong blood (plasma) flow effect. The analysis is followed by the realistic modeling and numerical simulations of alveolar gas diffusion in a straight capillary under blood flow, with RBCs represented as discrete circles. Results indicate a substantial increase in the gas diffusion efficiency with blood speed, especially under low hematocrit and high blood speed. Der Einfluss der Bewegung roter Blutkorperchen auf die alveolare Gasdiffusion Bestehende Meinungsunterschiede uber den Einfluss des Blutstromes - genauer dem Fluss roter Blutkorperchen (RBC) - auf die alveolare Gasdiffusion werden untersucht. Im Gegensatz zum grundlegenden Verstandnis von Stromungseffekten (Konvektion) scheint ein Konsens uber die vernachlassigbare Rolle des Einflusses des Blutstroms auf den alveolaren Gastransport zu existieren. Dem widersprechend deuten experimentelle Beweise auf einen Anstieg der Effektivitat von alveolaren Gasaustausch mit steigenden Herzzeitvolumen (Antsrengung) hin, was leicht als Ergebnis verstarkten Blutstroms erklart werden konnte. Eine theoretische Analyse eines vereinfachten kapillaren Blutstroms, in welchem Blut als homogene Flussigkeit betrachtet wird (keine RBCs), wird prasentiert um den starken Blut- (Plasma-)Stromungseffekt zu demonstrieren. Der Analyse folgt die realistische Modellierung und numerische Simulation von alveolarer Gasdiffusion in einer geraden Kapillare mit Blutstrom und RBCs, reprasentiert als diskrete Kreise. Die Ergebnisse deuten einen substantiellen Anstieg der Gasdiffusionseffektivitat mit steigender Blutstromungsgeschwindigkeit an, besonders fur niedrige Hamatokritwerte und hohe Blutstromungsgeschwindigkeiten.

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.

Untested assumptions have been made with regard to functional dead space in facemasks, filters and breathing systems used in children for the administration of inhalation anaesthesia. Total functional dead space was measured in various combinations of this equipment applied to a spontaneous ventilation lung model with parameter settings appropriate for infants of 7-8 kg. We found that functional dead space was too large to allow for spontaneous ventilation of the lungs when a breathing filter was fitted. There was minimal relationship between size of the facemask and functional dead space; however, the provision of 22-mm female inlets to facemasks achieved proportionately less functional dead space than with 15-mm male inlets. Regardless of the apparatus used and the magnitude of the dead space, the leak induced when a poorly fitting facemask was used dramatically reduced the dead space of the breathing system - to near optimal conditions - by moving the alveolar gas elimination point to within the facemask itself.

Highland areas 3,000 m above sea level are called plateaus, and air pressure and oxygen partial pressure are relatively lower here than in the plains. Hypoxia occurs when people enter highland areas a short time after living in the plains, or after having originally lived in high altitude regions but stayed in the plains for a period of time. When they return to the highland area, they suffer from headache , dizziness , cardiopalmus, and shortness of breath. Some people even suffer from decreased food appetite, nausea, vomiting, insomnia, fatigue, abdominal distension, tightness of the chest, cyanotic lips, and limb numbness. The pathogenesis involves the slowing of oxygen exchange between the atmosphere and alveolar gas and of oxygen release from the blood, which causes organism hypoxia and high altitude sickness.

Nitric oxide (NO) is a novel indicator gas for investigating alveolar capillary gas exchange conditions. In clinical practice, pulmonary gas uptake is determined by measuring the single-breath diffusing capacity (DL,NO). Different algorithms are employed to calculate DL,NO. To compare the accuracy of those most commonly used, we performed single-breath experiments on 12 artificially ventilated rabbits. In each animal four manoeuvres, executing breath-holds of 2, 4, 6 and 8 s, were carried out. In each case we administered 55 ml of an indicator gas mixture containing 0.05% NO. Alveolar gas was analysed by respiratory mass spectrometry. The two algorithms for calculating DL,NO based on the conventional solution of the breath-holding equation [Ogilvie et al. (1957) J Clin Invest 36:1-17 and Jones and Meade (1961) Q J Exp Physiol 46:131-143], were compared with the three-equation technique [Graham et al. (1980) IEEE Trans Biomed Eng 27:221-227] as the reference. The deviation between DL,NO calculated from the conventional methods and the reference decreased linearly with increasing duration of NO uptake (deltat). The mean deviations declined from 16.6% (Jones and Meade) or 7.7% (Ogilvie) at deltat=4 s to 5.7% (Jones and Meade) or 2.4% (Ogilvie) at deltat=10 s. The larger mean values are due to the conventional solution where three-tenths of the inflation time is subtracted from deltat. These findings qualify the common prediction that the latter method yields DL,NO values of the highest accuracy. We therefore recommend Ogilvie's procedure if the three-equation technique cannot be employed.

We have presented a minimally invasive method based on vascular injection of hyperpolarized 129Xe in saline to generate MR images with contrast driven by pulmonaryperfusion and xenon gas exchange.