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The Bohr model of the lung is examined, and all assumptions involved are specified. The weakest assumptions are those required to produce constant alveolar gas concentrations, e.g., simultaneous inhalation and exhalation; these lead to a “static” model. With more realistic assumptions we arrive at a dynamic version of the Bohr two-compartment model. Computed solution of the equations of this model demonstrates two phenomena, i.e., cardiogenic oscillations and increasing carbon dioxide/decreasing oxygen tension in the exhaled gas, not shown by the static model. Experimental results for the changes in exhaled gas concentration are in fair agreement with the model results. It is interesting to observe that the alveolar gas concentrations computed with this lumped parameter model are very similar to the corresponding curves from the distributed parameter model presented by Flumerfelt and Crandall [3].

Physiologic dead space has been measured in five cases of the Hamman-Rich syndrome using arterial carbon dioxide tension for alveolar carbon dioxide tension. At rest physiologic dead space was increased in three cases, sometimes grossly. The dead space/tidal volume ratio was elevated in all cases. On exercise physiologic dead space increased greatly; its ratio to tidal volume showed no appreciable change from the resting ratio and was excessive in all cases. The increase was too great to be accounted for by errors in the method or an artefact caused by venous admixture. It is attributed to the development of focal emphysema. Increase in dead space correlates well with, and is believed to account partially for, clinical severity. In this condition the dead space is too high at rest and on exercise for one to obtain "alveolar air" by end tidal sampling. Similarly the assumption of a dead space is unjustified. The meaning of "physiologic dead space" is discussed. Attention is drawn to the fact that it must be defined in terms of blood gas and not alveolar gas tensions, since the term itself implies our inability to choose any sample of air as representative of alveolar air.

The first part of this paper reviews two recent methods for obtaining mixed venous blood gas tensions. In the first ( Kim et al., 1966), Pvco2 is obtained from analysis of the change in alveolar gas composition during a single expiration. In the second ( Cerretelli et al., 1966a), both PvO2 and PvcO2 are obtained by rebreathing. Both techniques are well suited to study during exercise. When the Pv values thus obtained are used to calculate pulmonary blood flow (cardiac output in the normal man during steady state), it is necessary to know the alveolar gas tensions, the alveolararterial tension differences and the blood dissociation curves for the subject under study. The sources of error in this procedure are reviewed.

Oxygen capture in the lung results from the intimate dynamic interaction between the space- and time-dependent oxygen partial pressure that results from convection-diffusion and oxygen extraction from the alveolar gas and the space and time dependence of oxygen trapping by the red blood cells flowing in the capillaries. The complexity of the problem can, however, be reduced due to the fact that the systems obey different time scales: seconds for the gas phase transport and tenths of seconds for oxygen trapping by blood. This results first from a dynamical study of gas transport in a moving acinus and second from a new theory of dynamic oxygen trapping in the capillaries. The global solution can be found only through a self-consistent iterative approach linking the two systems. This has been accomplished and used to quantify oxygen capture in various situations: at rest, during exercise, ventilation–perfusion mismatching, high altitude and pulmonary edema.

Using glass electrode catheters, a decrease in blood plasma pH was found in four dogs when the electrode at the tip of the catheter was passed from central to more peripheral sites of the arterial system. This findings can at least in part be explained by assuming that in the lung capillaries erythrocytes and plasma equilibrate separately with alveolar gas.

In two normal subjects, the effect of changing lung volume on the uniformity of pulmonary diffusion (uniformity of Dl/Vl) was studied using the breath-holding and equilibration methods. Nonuniformity of diffusion, as indicated by deviation from a true exponential in the disappearance of carbon monoxide from alveolar gas, was seen to increase with increasing lung volume. Over-all Dl increased significantly with increasing lung volume. When lung volume was controlled, equilibration and breath-holding diffusion methods yielded similar over-all Dl and similar variation in Dl/Vl throughout the lung. Submitted on January 29, 1959

Transitory contact of ethanol with the mucous membranes of the mouth or nasal passages, or both, is sufficient to drastically alter measurements of concentrations of ethanol in so-called "alveolar" gas for more than 20 minutes after such contact. Various concentrations of ethanol were taken into the mouth by human subjects and were expectorated. Readings of so-called "blood alcohol" were then taken at short intervals by means of the Breathalyzer(R) and were continued up to 1 hour after exposure. These readings were compared with blood-alcohol concentrations measured by quantitative chemical analysis of venous blood. When true concentrations of blood alcohol were at or close to zero (plus possible error of 0.0001 gram per 100 milliliters), readings of greater than 0.40 gram per 100 milliliters were obtained on the Breathalyzer. Repeated mouth washing and gargling with water, changes in the nature of the solvent, and stomach loading each had only a slight effect in diminishing these errors.

SummaryCO2 elimination of anesthetized dogs was temporarily reduced after injection of carbonic anhydrase inhibitor. Reduction was greater for dogs in which ventilation was held constant than for dogs ventilating spontaneously. Results indicate that increased gradient for Pco2 from tissues to the alveolar gas is essential for reestablishing a steady state of CO2 elimination when carbonic anhydrase is inhibited. The required increase in this gradient can be produced by means of augmented ventilation, by increased tissue Pco2, or by combination of these 2 factors.

The concentration of acetone in arterial blood may be determined by vapor phase chromatographic analysis of alveolar gas. Alveolar gas may be considered as a biological specimen preferable to blood. It is easily obtained, does not require anticoagulant or refrigeration for storage, and analysis by vapor phase chromatography is speedily and easily achieved.

When pulmonary diffusing capacity for O2 is to be determined in lungs with unequal distribution of alveolar ventilation to pulmonary perfusion it is common practice to correct arterial PO2 for the shunt effect and the end-tidal PO2 for alveolar dead space ventilation. The latter correction is based on the assumption that PCO2 in end-capillary blood is in equilibrium with alveolar gas (Riley and Cournand, 1949). It appears to follow from this assumption that in conditions of no gas exchange, such as rebreathing, PCO2 in alveolar gas should be equal to that in arterial blood. Thus the finding of negative blood-to-gas PCO2 differences during rebreathing in dogs (Gurtner et al., 1969) and in man (Jones et al., 1969, 1972; Denison et al., 1971) has challenged the fundamental concepts of pulmonary gas exchange. However, these results could not be reproduced by others (Scheid et al., 1972).

Three commonly employed anesthesia circle systems were tested to determine what effect the placement of the inflow port, overflow valve, and inspiratory and expiratory valves, as well as inflow rate, had on the rate of rise of anesthetizing alveolar concentrations of halothane. System efficiency was evaluated on the basis of whether alveolar gases, containing low concentrations of halothane, or fresh and deadspace gases, containing higher concentrations of halothane, were eliminated through the overflow valve. Small potentially significant differences in efficiency were found: greatest efficiency (greatest ejection of alveolar gas) occurred when inspiratory and expiratory valves were close to the endotracheal tube and the overflow valve was immediately distal to the expiratory valve. Increasing inflow rate from 1 to 3 L/min had a large impact on the rate of rise of alveolar halothane concentration. A further increase to 5 L/min had a relatively small effect.

By studying the behavior of various tracer species in the lungs, one can assess many important characteristics which distinguish normal and abnormal function. Quantitative evaluation of function depends on the use of an appropriate model in conjunction with experimental data. A multi-compartment model is derived from mass balances to describe dynamic as well as (breath-averaged) steady-state transport processes between the environment and pulmonary capillary blood. The breathing cycle is divided into three time periods (inspiration, expiration, and pause) so that the model equations are discrete in time. No other model of tracer species transport in the lungs deals simultaneously with species dynamics, variable breathing pattern, distribution inhomogeneities, and non-equilibrium between alveolar gas and capillary blood. Models currently in the literature are shown to be special cases of the model presented here.

A mathematical model has been implemented for evaluation of methods for estimating breath-to-breath alveolar gas exchange during exercise in humans. This model includes a homogeneous alveolar gas exchange compartment, a dead space compartment, and tissue spaces for CO2 (alveolar and dead space). The dead space compartment includes a mixing portion surrounded by tissue and an unmixed (slug flow) portion which is partitioned between anatomical and apparatus contributions. A random sinusoidal flow pattern generates a breath-to-breath variation in pulmonary stores. The Auchincloss algorithm for estimating alveolar gas exchange (Auchincloss et al., J. Appl. Physiol. 21: 810-818, 1966) was applied to the model, and the results were compared with the simulated gas exchange. This comparison indicates that a compensation for changes in pulmonary stores must include factors for alveolar gas concentration change as well as alveolar volume change and thus implies the use of end-tidal measurements. Although this algorithm yields reasonable estimates of breath-to-breath alveolar gas exchange, it does not yield a “true” indirect measurement because of inherent error in the estimation of a homogeneous alveolar gas concentration at the end of expiration.

1. Atropine is known to diminish broncho-motor tone. In order to investigate the acute effect of atropine on respiration and alveolar gas mixing, a dose of 2.4 mg was given intravenously. 2. Ten normal male volunteers were each studied three times with a nitrogen washout method, once before administration of atropine and then 20 min and 60 min thereafter. 3. After the administration of atropine there was a reduction in tidal volume, a slight increase in frequency of respiration and an increase in series dead space. The tidal mixing volume showed a fall of 25%. In spite of the reduced alveolar dead space the effective mixing volume fell by 29%. Multi-breath alveolar mixing efficiency fell by 3.5%. 4. Multi-breath alveolar mixing efficiency was found to be less with smaller tidal mixing volumes, a fall of 518 ml in the latter causing a reduction of 17.2% in mixing efficiency. 5. A reduction of 100 ml in tidal volume in normal subjects was associated with a decrease of 6.9% in alveolar mixing efficiency. In the subjects receiving atropine tidal volume reduced by 96 ml, but the observed fall in alveolar mixing efficiency was only 3.5%, This suggests an improvement in alveolar mixing of 3.4% due to the administration of atropine. Despite this small improvement, the mixing efficiency is still only 66%. The residual inefficiency of 34% cannot therefore be explained on the basis of broncho-motor tone.

Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT′) with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT′). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT′ occurred during all aerosol challenges and were correlated with decreases in Cdyn (r = 0.84, P less than 0.001). Decreases in VT/VT′ were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT′ was 3.1–4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT′ returned to base line after histamine exposure was stopped. We conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT′ ratio appears to provide a simple noninvasive method of detecting these changes.

The performance of an infra-red analyser (Beckman LB-2) in sampling alveolar gas at ventilatory frequencies and volumes occuring in the human neonate has been examined. The optimum sampling flow rate was found to be 300 ml/min; at this flow the 90% response time of the analyser-catheter system was 140 ms. Correlation of estimated alveolar PCO2 and arterial PCO2 was performed in the rabbit which has a ventilatory rate and tidal volume similar to those of the human neonate. There was a good correlation between maximum end-expired PCO2 (PE'CO2) and arterial PCO2 over a wide range of ventilatory rates (10-100 b.p.m.); maximum PE'CO2 was a better index than mean PE'CO2 or alveolar plateau PE'CO2.

A mechanical alveolar gas sampler using the revolver principle capable of collecting six individual expired gas samples is described. The 0.91-kg sampler collects 19-ml samples in pre-evacuated aluminum ampoules equipped with spring-loaded valves from a sampling chamber equipped with two removable one-way valves. On depression of external handles, one of six ampoules located in a removable cartridge is aligned and advanced into the sampling chamber where its valve is opened and then closed. Releasing the handles removes the ampoule from the sampling chamber and automatically rotates the cartridge through 60 degrees to position a new ampoule in preparation for the next sampling sequence. A lock-out mechanism prevents reexposure of any of the ampoules after six samples have been taken. The performance of the sampler is described including its successful use in the field to collect alveolar gas samples on the summit of Mount Everest.

Respiratory responses to a single breath during which a resistive load was applied were studied in 8 conscious subjects. There was an increase in inspiratory time (TI), an increase in end-tidal PCO2 (PETCO2) and a decrease in end-tidal PO2 (PETO2) on the resisted breath. 12 subjects were given a single inspiration of a mixture of air containing increased CO2 and reduced O2. This gas mixture induced changes in PETCO2 and PETO2 approximately double those seen with the resistive loads. There was no change in tidal volume (VT), TI or expiratory time during the first breath. During the following breath there was a small increase in TI and VT. The results indicate that although resistive loading may cause changes in PETCO2 and PETO2, these changes are unlikely to contribute to the respiratory responses during the first loaded breath.

The purpose of this study was to investigate the mechanism that causes a damped oscillatory response of local pulmonary blood flow to local hypoxia. The left lower lobe (LLL) of 10 anesthetized dogs was ventilated independently but synchronously with the rest of the lungs. Blood flow to the LLL as a proportion of total flow (QLLL/QT) was measured during the on-transient of the hypoxic response when LLL inspirate was changed from O2 to N2. There was a damped oscillatory response of QLLL/QT to hypoxia (34 of 40 trials). In contrast, the off-transient was always monotonic. There was no enhancement of the steady state or dynamic hypoxic response with repeated challenges. Local alveolar hypercapnia caused a damped oscillatory response in the presence of local hypoxia (15 of 20 trials), but there was no response in the presence of local hyperoxia. We conclude that 1) the dynamic pulmonary vascular response to O2 and CO2 are not additive because the response to CO2 is attenuated by hyperoxia and 2) the damped oscillatory response that occurs during hypoxia is the result of changes of local alveolar CO2 per se.

Maximal expiratory flow rate (Vmax) was measured at 20, 35, 50, 65, and 80% vital capacity in 4 young healthy subjects breathing air, SF6/O2, and He/O2 mixtures. The flows of SF6/O2 and He/O2 were corrected to normal alveolar gasflow by means of only the density of the gases. The values for normal alveolar gasflow and corrected SF6/O2 flow were identical at 35% VC and larger volumes while the values for normal alveolar gasflow and corrected He/O2 flow were not. The results indicate that in young healthy subjects it is possible to correct Vmax at lung volumes above 359: VC for the changes induced by an increase in density of the gas breathed, provided viscosity is not much changed. Without correction, Vmax after O2-breathing will be underestimated by about 6%, compared with Vmax for normal alveolar gas, whereas a change in alveolar CO2 concentrations between 3 and 9% only causes a 1 % decrease of V max.

This review describes the transport of oxygen from ambient air to mitochondria in the cells. Using simple equations and diagrams, the presentation illustrates the variables which determine the magnitude of each of the three major steps in the partial pressure of O2 along the passage, from: (i) ambient air to alveolar gas; (ii) arterial blood to venous blood; and (iii) capillary blood to tissue. The emphasis is on steps (ii) and (iii), and how they are modified from the normoxic case by ischemia, anemia, hypoxia, and increased VO2. The basic context of step (iii) is the Krogh model. This model, despite its limitations, is proposed as conceptually useful in analyzing whole-body or tissue O2 transport.

We have compared the results of gas analysis by respiratory mass spectrometry using long (30 m) sampling probes with those obtained using conventional short (1.3 m) probes, examining both static gas mixtures and respired gas at the mouth during manoeuvres designed to make the concentrations of inspired marker gases change in a complex way within a breath. The experiments showed that no important errors were introduced by using the long probes, both for estimates of gas tensions and for derived physiological variables. A slight reduction in signal for a water-soluble component was noted when sampling a moist gas mixture with a long probe, but again this was of no practical significance. Ways in which the use of long sampling probes increase the versatility of the respiratory mass spectrometer are discussed. In essence they enable a greater range of subjects to be studied, they allow simultaneous events to be examined sequentially and they permit a single instrument to be shared between several patients or laboratories.

Expiratory pressure-volume curves and maximal expiratory flow-volume curves were obtained in 74 healthy subjects (49 males 25 females) aged between 20 and 64. Maximal expiratory flowstatic recoil (MEFSR) curves were then constructed. Aging was associated with loss of lung recoil and reduction in maximal expiratory flow measured between 80 and 50% total lung capacity (TLC), in both males and females, with the slope of the MEFSR curve becoming steeper. In subjects less than 40 yr old the conductance of the upstream segment increased from 80 to 50% TLC, whereas in older subjects it decreased. We also studied the effects of alveolar gas compression artifacts on MEFSR curves in 12 additional subjects and 10 patients with chronic obstructive lung disease; consistent changes were found, but the subsequent shift of the MEFSR curve toward the left was only mild. These changes are interpreted as reflecting the net effects of an increase in the unstressed dimensions of the airways together with a decrease in intraparenchymal airways diameter, probably due to loss of parenchymal airways diameter, probably due to loss of parenchymal support. It was also concluded that the analysis of the MEFSR curve did not allow a quantitative estimate of the chantes in airways compressibility with aging.

A new method of artificial ventilation, intermittent high frequency ventilation (IHFV), is described in which high frequency ventilation (HFV) is intermittently interrupted so that short periods of ventilation and pauses in ventilation occur in sequence several times a minute. During the pauses in ventilation the increase in lung volume, which occurs during the short periods of HFV, is either exhaled completely or to a predetermined level which prevents sustained hyperinflation of the lungs but allows the maintenance of PEEP if required. The volume of gas expired during the ventilation pauses, i.e. gas retained during the periods of HFV, is measured. When this trapped gas is exhaled completely, the mean airway and compliance pressures are reduced by up to 50% compared to continuous HFV at the same frequency, inspiration:expiration (I:E) ratio and low tidal volume (VT). The alveolar CO2 concentration was measured in gas expired towards the end of the pauses in ventilation. CO2 elimination was improved, especially at high frequencies of ventilation, which allowed a further reduction in inflation pressures while maintaining a constant Paco2.

Tracheal and alveolar gas composition was studied by mass spectrometry in a patient with severe ARDS treated by low frequency positive pressure ventilation/extracorporeal CO2-removal (LFPPV-ECCO2R). Measured alveolar gas concentrations were compared with values derived from standard respiratory equations. As a result we found that during LFPPV-ECCO2R with a constant endotracheal O2-flow, alveolar gas composition cannot be predicted reliably from standard equations. The reasons for this finding are discussed. We conclude that monitoring of alveolar gas composition by mass spectrometry is of great value during LFPPV-ECCO2R if PAO2, P(A-a)O2 and Qva/Qt are to be determined correctly.

Three experimental studies were undertaken in our laboratory with the aim of reproducing and checking previous experimental findings which had indicated that blood-gas CO2 equilibration in lungs led to a condition in which \({{\text{P}}_{C{O_2}}}\) in alveolar gas was higher than in blood.

290 22nd ASPEN LUNG CONFERENCE CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT 4 Knudson RJ, Armet DB, Lebowitz MD: Reevaluation of tests of small airways function. Chest 77:284, 1980 5 McCarthy DS, Spencer R, Greene R, et al: Measurement of “closing volume” as a simple and sensitive test for early detection of small airway disease. Am J Med 52:747-753, 1972 6 Cherniack RM, McCarthy DS: Reversibility of abnormalities of pulmonary function. In The Lung in the Transition between Health and Disease, Chapter 15 (Lung Biology in Health and Disease, Vol 12) (Macklem P. Permutt S, eds) New York, Marcel Dekker, 1979, pp 329-342

Ethane quantitated in the expired alveolar gas is a noninvasive measure of free radical activity. This method has been criticized for lack of control of minute ventilation (VE) in spontaneously breathing animals, although ethane, which is poorly soluble in tissues, should not be affected by changes in VE. We measured ethane elimination rates in six strain 13 guinea pigs (GP13) during spontaneous room air breathing and in six room air breathing, pentobarbital-anesthetized, tracheostomized, externally warmed, mechanically ventilated GP13s at various levels of VE. In the ventilated animals, weight0.75/VE (metabolic activity corrected for VE) was a linear function of arterial CO2 tension (PaCO2) drawn from arterial line (r = 0.72, P less than 0.005). However, weight0.75/VE did not correlate with ethane elimination rates (r = 0.12, not significant). The mean (+/- SD) ethane elimination rates in the spontaneously breathing animals was 3.15 +/- 0.96 pmol.min-1.100 g-1 and was not significantly different from the mean rate in the mechanically ventilated animals (3.11 +/- 1.37) over a range of VE's. These data demonstrate that ethane elimination rates are not affected by changes in VE and are unaffected by pentobarbital anesthesia.

We evaluated the usefulness of end-tidal CO (ETCO) as an internal standard for reducing the error in end-tidal H2 (ETH2) measurements due to contamination of repeated breath samples with nonalveolar gas. Triplicate end-tidal samples were drawn from 12 healthy premature infants in small (less than 1 cc) increments through a posterior nasopharyngeal catheter at end-expiration, determined from the infant's chest wall movement. CO and H2 determinations were made on each sample by a reduction gas detector capable of determining CO and H2 concentrations to +/- 0.001 and 0.010 ppm, respectively. Respiratory breath samples were corrected for ambient CO and H2 concentrations. Since the alveolar gas fraction has the highest CO concentration of all tidal gases, the end-tidal sample with the highest CO peak was assumed to be most representative of uncontaminated alveolar gas. The other samples were "corrected" using a factor that was the ratio of the patient's highest CO peak to the given sample's CO value. The use of ETCO to correct ETH2 from samples deliberately contaminated with ambient air can significantly reduce the variability of ETH2 values. However, such correction is probably not necessary when comparing groups of infants using a standard collection technique. For individual infants, correction may reveal more marked short-term fluctuations in true alveolar H2 concentration.

After overnight-fasting, the concentration of dimethyl sulfide in expired alveolar gas (alv-DMS) was determined serially following ingestion of 2 g of DL-methionine in normal subjects and patients with liver diseases. Alv-DMS rose to a peak in 30 to 90 min, declined markedly within 3 h, and then decreased gradually. Half-disappearance times (T 1/2) (mean +/- S.E. min) in each experimental group were: normal (N = 9) 61.7 +/- 4.7, acute hepatitis (N = 6) 62.5 +/- 6.8, chronic hepatitis (N = 10) 84.0 +/- 13.0, and liver cirrhosis (N = 13) 159.2 +/- 30.4, respectively. Cirrhotics had a T 1/2 significantly longer than that of the other three groups: vs. normal P less than 0.02, vs. acute hepatitis P less than 0.05, and vs. chronic hepatitis P less than 0.05. T 1/2 of alv-DMS following ingestion of DL-methionine seems to be of clinical interest.

We know that the alveoli and the capillaries around the alveoli play an important role in gas exchange. It is also known that alveolar and capillary compliance contribute a major part to the total lung compliance. If these structures have a great compliance it must be possible to exert an influence on the alveolar gas compartment (inflating of ventilatory gases), which has an immediate effect on the capillary blood circulation. On the other hand, if the capillaries around the alveoli (the capillary meshwork) have a great compliance they must exert an influence on the alveolar gas compartment during right ventricular contraction, which fills the capillaries with blood, increasing the total interalveolar volume. The increase in interalveolar blood volume should lead to displacement of alveolar gases.

A computer program to measure breath by breath alveolar pressure (PA) and alveolar to arterial difference (AaD) for O2 and CO2, by a mass-spectrometer has been implemented. The program allows the determination of alveolar gas by different methods: 1. Bohr's equation (BE); 2. ideal alveolar air equation for O2 (IDO2); 3. end-tidal (ET); 4. by the Rahn's definition of 'mean alveolar gas', i.e., alveolar pressures are defined when instantaneous respiratory exchange ratio (IRQ) equals mean respiratory exchange ratio (MRQ). This automated technique has been used in 16 patients with chronic obstructive lung disease (COLD) and 15 patients with pulmonary embolism (APE). In both groups of patients it was always possible to find in each breath the point where IRQ = MRQ and therefore to measure AaD by RD. IDO2 was significantly lower than PAO2 by the other methods. Also ET values of O2 and CO2 were significantly different from RD and BE in both groups of patients, however the difference was consistently higher in COLD patients. The different shape of the expirograms (steeper expirograms in COLD) is responsible for this different result. RD and BE AaD characterize gas exchange more precisely than ET, because the contribution of high VA/Q units is also evaluated. This is particularly important in COLD patients. Consideration on dead space measurements are also reported both for COLD and APE patients. In conclusion this automated technique provides the assessment of gas exchange for the use in clinical respiratory physiology and for the monitoring of gas-exchange in critically ill patients.

Cyclic rebreathing of a soluble inert gas can be used to estimate lung tissue volume (Vt) and pulmonary blood flow (Qc). A recently proposed method for analyzing such cyclic data (Respir. Physiol. 48: 255–279, 1982) mathematically assumes that ventilation is a continuous process. However, neglecting the cyclic nature of ventilation may prevent the accurate estimation of Vt and Qc. We evaluated this possibility by simulating the uptake of soluble inert gases during rebreathing using a cyclic model of gas exchange. Under cyclic uptake conditions alveolar gases follow an oscillating time course, because gas concentrations tend to increase during inspiration and to decrease during expiration. We found that neglecting these alveolar gas oscillations leads to the underestimation of soluble gas uptake by blood, particularly during the early rebreathing breaths. When continuous ventilation is assumed Vt and Qc are overestimated unless rapid rebreathing rates, large tidal volumes, and gases of moderately low solubility are used. Under these conditions the amplitude of the cyclic oscillations is minimized, the alveolar time course more closely resembles that expected from continuous ventilation, and the resulting errors are minimized. Alternatively, when the effect of oscillating alveolar gas concentrations on mass transfer are considered, these estimation errors can be eliminated without restricting rebreathing rate or gas solubility. We conclude that failure to consider the effect of cyclic rebreathing on the time course of alveolar gas concentrations may result in significant errors when evaluating rebreathing data for Vt and Qc.

Mouth breathing in response to an impaired nasal airway is thought to have clinical consequences. Physiologically, mouth breathing occurs whenever the body senses that nasal resistance is inappropriately high. In physical terms mouth breathing is a response that enlarges the upper airway and, by doing so, reduces airway resistance. In the past measurements of nasal resistance have been used as an index of airway impairment. Recently, we introduced a technique that estimates cross-sectional size of the airway, a variable that directly determines the magnitude of airway resistance. The purpose of the present study was to determine the precise effects of nasal airway size on nasal airway resistance so that the relationship between the two could be described in mathematic terms. There were two phases to the study--one involving a model and simulated breathing, and the other involving 100 subjects demonstrating normal and impaired nasal airways. The pressure-flow technique for estimation of nasal airway size and nasal airway resistance was used. The following equation was generated from the data: Resistance = 1.9 + (Formula: see text). The relationship between the two variables is nonlinear--that is, size of the airway has its greatest effect on resistance when the airway is less than 0.4 cm2 and a much lesser effect at larger airway sizes. The study also showed that nasal airway resistance generally does not fall very much below 1.9 cm H2O/L/S during breathing even when the airway is very large. This probably relates to the need to maintain an adequate level of airway resistance for alveolar gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

The idea of measuring the specific diffusing capacity of the lungs for carbon monoxide (DL/VA) as an index of the condition of the “alveolar-capillary membrane” was introduced in 1915 by M. Kroghl. She showed that during short periods of breath-holding with the glottis open the removal of CO from alveolar gas by the hemoglobin was a first order reaction and proposed that the time constant of the exponential decay of alveolar CO during breath-holding be used as a measure of the size of the “alveolar capillary membrane”. This time constant $$=\frac{1}{t}~~.1n{{\frac{{{F}_{{{A}_{CO}}}}}{{{F}_{{{A}_{CO}}^{\prime \prime }}}}}^{\prime }}~\frac{1}{B-47}~~where~t~~is~the$$ period of breath-holding,\({{F}_{{{A}_{CO}}}}^{\prime }\)is the alveolar CO concentration at the beginning of the period of breath-holding,\({{F}_{{{A}_{CO}}}}^{\prime }\)is the alveolar CO concentration at the end of the breath-holding period and B is barometric pressure. The term specific diffusing capacity (DL/VA) was introduced by Ayers et al in 19752. It is directly proportional to Krogh’s time constant i.e. $${{F}_{{{A}_{CO}}}}^{\prime }$$ But the use of DL/VA or Krogh’s time constant in this manner assumes that the time required for CO to combine chemically with hemoglobin is negligible compared to the time required for CO to diffuse across the alveolar-capillary membrane. In 1957 it was shown that the rates of the two processes, diffusion and chemical combination with hemoglobin are of the same order of magnitude3. Consequently DL/VA is only an index of the condition of the membrane, not an actual measurement.

With modern methods of measuring carbon monoxide in air, or in workers themselves, now widely available and well tested, it should be mandatory that these techniques be applied wherever carbon monoxide exposure is likely to be frequent in the work place. The relative merits of area, personal, and individual biological monitoring of exposure are discussed. While continuously recording area monitors and portable or personal samplers are useful, supplementation of these techniques by alveolar gas or blood measurements is often necessary.

This is an experimental and theoretical analysis of the Mapleson D (Bain) circuit. A bench model was used to determine the effects of breathing rate, tidal volume, and fresh gas flow on the simulated alveolar gas composition when a commercial Bain breathing circuit is used. In addition, an effort was made to derive mathematical equations that describe the CO2-profile in the expiratory limb of the Bain circuit, the amount of CO2 rebreathed, and the effect of this rebreathing on the alveolar gas composition. Data obtained with the bench model and with the equations were compared to data from the literature. The effect of the Bain circuit on gas exchange was compared to that of an equivalent dead space.

Changes in expired alveolar O2 and CO2 were measured breath-by-breath in six healthy male subjects (mean age 30 yr, mean weight 80 kg) at rest, 600 kpm/min, and 1,200 kpm/min. Changes were expressed in relation to expired volume (liters) and time (s) and separated into an initial dead-space component using the Fowler method applied to expired CO2 and O2, and alveolar slope. The alveolar slopes with respect to time (dPACO2, dPAO2, Torr/s) increased in relation to CO2 output (VCO2, 1/min, STPD) and O2 intake (VO2, 1/min, STPD) but were reduced by increasing tidal volume (VT, liters, BTPS): dPACO2 = 2.7 + 4.6(VCO2) - 1.9(VT) (r = 0.97); and dPAO2 = 2.3 + 5.5(VO2) - 1.9(VT) (r = 0.96). From the alveolar slopes, tidal volume, and airway dead-space volume, mean expired alveolar PO2 and PCO2 (PAO2, PACO2) were calculated. There was no change in arterialized capillary PCO2 (PaCO2) between rest (38.9 +/- 0.66 Torr) and heavy exercise (38.2 +/- 2.18 Torr), but mean PACO2 rose from 36.7 +/- 0.55 to 40.8 +/- 1.67 Torr during heavy exercise. There was no change in arterialized capillary (mean = 84.3 +/- 0.7 Torr) or alveolar (mean = 107.2 +/- 1.03 Torr) PO2. Exercise increases the fluctuations in alveolar gas composition leading to discrepancies between the PCO2 in mean alveolar gas and arterial blood to an extent that is dependent on VCO2 and VT.

studies of the high-altitude natives in the South American Andes focused attention for the first time on aspects of respiratory adaptation that were different from those of sojourners at the same high altitude (4, 9, 12, 28; see also 7, 14, 15). Previously it was thought that the level of adaptation in the fully acclimatized sojourners would be the same as in the native high-altitude residents (1; see also 9). To understand high-altitude adaptation, researchers at the Andean Institute of Biology in Peru compared sea-level natives and high-altitude natives in their own respective environments. Recently respiratory control has gained particular attention because of the striking observation that the adult natives of high altitude ventilate less at a given resting metabolic rate so that their partial pressure of carbon dioxide in alveolar gas (PaCO2) is higher and partial pressure of oxygen in alveolar gas (PaO2) lower (4, 13, 14). It was also established that hyperpnea of exercise was less in the high-altitude natives than in the sojourners (14, 15).

In recent years, a number of investigators have observed that arterial and/or mixed venous \({{\text{P}}_{C{O_2}}}\) can be lower than alveolar \({{\text{P}}_{C{O_2}}}\) during conditions when no CO2 is exchanged in the lung capillaries. The range of values reported for these differences has been exceptionally wide. For example, in one laboratory, careful studies with several different preparations failed to reveal any \({{\text{P}}_{C{O_2}}}\) differences between alveolar gas and blood [7]. Other laboratories have reported that the \({{\text{P}}_{C{O_2}}}\) differences can become quite large during exercise [6] or acidosis [5]. The wide range of reported values probably reflects the many technical difficulties involved in obtaining such data. Several explanations have been proposed for these differences, but none has been entirely accepted to date.

Oxygen moves down a partial pressure gradient from inspired gas, through alveolar gas, arterial blood, systemic capillaries and cells, to reach its lowest level within the mitochondria where it is consumed (Figure 1). The steps by which the Po2 decreases from inspired gas to the mitochondria are known as the oxygen cascade and are of great practical importance. Any one step in the cascade may be increased under pathological circumstances and this may result in hypoxia. Within limits, the effect of certain increased steps in the cascade can be offset by raising the concentration of oxygen in the inspired gas. However, the quantitative relationships are totally different depending on which step in the cascade is abnormal.

A black box and a geometrical approach have been used to deduce the relationships between alveolar oxygen and carbon dioxide concentrations when rebreathing occurs during the use of semi-closed anaesthetic rebreathing systems.

The determination of alveolar to arterial differences (AaD) is a simple and available method to determine the overall efficiency of gas exchange. AaD are strongly related to the measurement of alveolar gas, and the different methods commonly used to measure alveolar gas concentrations are not able to give an estimate of the “mean alveolar gas”.

The behaviour of the anatomical dead space cannot be described by passage of a ‘square’ wave front through the conducting airways, with subsequent diffusion of alveolar gas back up the bronchial tree.

During 16 bronchopulmonary lavages on nine patients, only mild hypoxemia developed. Since blood perfusing the liquid-filled lung is not exposed to alveolar gas, this suggests decreased perfusion of the lavaged lung. During four lavages, the degree of perfusion of the lavaged lung was shown to increase with the difference between the pressure in the pulmonary artery and the hydrostatic pressure of fluid filling the lavaged lung. To increase the safety of bronchopulmonary lavage, one should use high concentrations of inspired oxygen, maintain airway pressure of the lavaged lung above or as close as possible to pulmonary-artery pressure, and closely monitor arterial-blood gases.

The clearance rates of short-lived radioactive gases from defined areas of the lung have been used to measure regional blood flow and gas exchange. The clearance rates are measured by external counting over the chest during a short period of breath holding following a rapid inspiration of the gas. Two processes are necessary for the clearance of any radioactive gas from the counting field, namely, transfer from alveolar gas to pulmonary capillary blood, and subsequent removal of the active gas from the field. Recently it has been shown that oxygen-labeled CO2 is lost from alveolar gas exceedingly rapidly, and it can therefore be used to separate these two clearance rate processes. A theoretical analysis shows how that can be done, and experiments designed to test the theory are described. Although considerable approximations are necessary, the analysis clarifies the factors controlling the clearance rate of any radioactive gas. One consequence is that the large variations in the regional uptake of radioactive CO and O2 previously reported are probably overestimates. Submitted on December 7, 1960

Rebreathing from a bag containing a volume approximating the functional residual capacity of 8–9 % CO 2 in N 2 results in alveolar O 2 and CO 2 tensions which become stable four to eight sec after the beginning of rebreathing and are maintained for approximately six sec. These tensions are believed to reflect mixed venous blood tensions. Ranges at rest are from 35 to 52 mm for P O 2 and 44 to 47 mm for P CO 2 . During exercise, P O 2 decreases and at an oxygen uptake of two 1/min is of the order of 30 mm Hg. Cardiac output values calculated from these data agree well with figures obtained with another method.