Convection- and diffusion-dependent ventilation maldistribution in normal subjects

We performed multiple-breath N2 washouts (MBNW) with tidal volumes of 1 liter at 8-16 breaths/min and constant flow rates in six normal subjects. For each breath we computed the slope of the alveolar plateau, normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), an index analogous to the Fowler dead space (V50), and the normalized slope of phase II (S2). In four subjects helium (He) and sulfur hexafluoride (SF6) were washed out after equilibration with a 5% gas mixture of each tracer. The Sn for He and SF6 increased in consecutive breaths, but the difference (delta Sn) increased only over the first five breaths, remaining constant thereafter. In all six subjects Sn, VDB, and V50 increased progressively in consecutive breaths of the MBNW, the increase in Sn being the greatest, approximately 290% from the first to the 23-25th breath. In contrast, S2 was unchanged initially and decreased after the sixth breath. The results indicate that after the fifth breath the increase in Sn during a MBNW is diffusion independent and may constitute a sensitive index of convection-dependent inhomogeneity (CDI). Subtraction of this component from the first breath suggests that Sn in a single-breath washout is largely due to a diffusion-dependent mechanism. The latter may reflect an interaction of convection and diffusion within the lung periphery, whereas CDI may comprise ventilation inequality among larger units, subtended by more centrally located branch points.     

Model simulations of gas mixing and ventilation distribution in the human lung

A new lung model that incorporates intra-acinar diffusion- and convection-dependent inhomogeneities (DCDI) and interregional and intraregional convection-dependent inhomogeneities (CDI) is described. The model is divided into two regions, each containing two subunits. Each of the four subunits in the model consists of a multi-branch-point structure, based on the anatomic data from Haefeli-Bleuer and Weibel (Anat. Record 220: 401-414, 1988). The subunit turnover (TO), i.e., the ratio of subunit tidal to resting volume, and the flow sequences (FS) between the subunits are used as model parameters. The model simulates the normalized alveolar slope (Sn), Fowler and Bohr dead space (VDF and VDB), and alveolar mixing efficiency (AME) as a function of breath number (n) during a multiple-breath N2 washout (MBNW). For the first breath of the MBNW, these indexes are poorly sensitive to the TO distribution or FS between the subunits. However, as the washout proceeds, the n dependence of both Sn and VDB becomes markedly distinct for simulations with different TO and FS. VDF increases only slightly with n during the MBNW for a large range of TO and FS combinations, and AME is independent of FS. Comparison of published experimental observations with model simulations gave a consistent picture of ventilation maldistribution in the human lung. MBNW simulations in conditions of weightlessness, which will be performed shortly in Spacelab, suggest that it will be possible to evaluate quantitatively the intraregional elastic inhomogeneities in the human lung.     

Effect of airway closure on ventilation distribution

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.     

Multiple-breath washout experiments in rat lungs.

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.     

AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study

Background

Alveolar volume measured according to the American Thoracic Society-European Respiratory Society (ATS-ERS) guidelines during the single breath diffusion test can be underestimated when there is maldistribution of ventilation. Therefore, the alveolar volume calculated by taking into account the ATS-ERS guidelines was compared to the alveolar volume measured from sequentiallly collected samples of the expired volume in two groups of individuals: COPD patients and healthy individuals. The aim of this study was to investigate the effects of the maldistribution of ventilation on the real estimate of alveolar volume and to evaluate some indicators suggestive of the presence of maldistribution of ventilation.

Methods

Thirty healthy individuals and fifty patients with moderate-severe COPD were studied. The alveolar volume was measured either according to the ATS-ERS guidelines or considering the whole expired volume subdivided into five quintiles. An index reflecting the non-uniformity of the distribution of ventilation was then derived (DeltaVA/VE).

Results

Significant differences were found when comparing the two measurements and the alveolar volume by quintiles appeared to have increased progressively towards residual volume in healthy individuals and much more in COPD patients. Therefore, DeltaVA/VE resulted in an abnormal increase in COPD.

Conclusion

The results of our study suggest that the alveolar volume during the single breath diffusion test should be measured through the collection of a sample of expired volume which could be more representative of the overall gas composition, especially in the presence of uneven distribution of ventilation. Further studies aimed at clarifying the final effects of this way of calculating the alveolar volume on the measure of DLCO are needed. DeltaVA/VE is an index that can help assess the severity of inhomogeneity in COPD patients.     

Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fast real-time moment-ratio analysis of multibreath nitrogen washout in children

To apply real-time moment-ratio analysis to multibreath N2-washout curves (MBNW) from children, a new processor-controlled device was constructed. Flow and fractional N2 concentration (FN2) were each sampled by 200 Hz. An electromagnetic triple-valve system, with an instrumental dead space of 36 ml and a valve resistance of 0.3 cmH2O . l-1 . s, was connected in series with a pneumotachograph and an N2 analyzer (Ohio 720) placed next to the mouthpiece. A FORTRAN/MACRO program on a PDP 11/23 computer enabled measurement of inspiratory and expiratory flow and FN2 sampling by a 12-bit analog-to-digital converter. The fast real-time digital processing of the N2 and flow signals incorporated filtering, delay compensation, and corrections for the effects of changes in gas composition and temperature. MBNW dynamics of the lungs were studied in 17 healthy and 28 asthmatic children and in 16 patients with cystic fibrosis, evaluating the moment ratios of the washout curves as indices of the ventilation characteristics. Intrasubject variability of the moment ratios (m1/m0, m2/m0) and determination of functional residual capacity (FRC) varied between 6.3 and 14.7% (depending on which parameter is considered) and was comparatively lower than other indices previously investigated in adults. In addition, the sensitivity of the moment ratios for discriminating different stages of ventilation inhomogeneity was superior to other indices. m2/m0 is closely related to the simultaneously measured airway resistance, and the ratio between cumulative expired volume and FRC is correlated with the ratio between residual volume and total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas mixing in dog lungs studied by single-breath washout of He and SF6

Simultaneously measured helium (He) and sulfur hexafluoride (SF6) single-breath washout was studied in 16 anesthetized paralyzed dogs ventilated with a special hydraulically operated ventilatory servo system. After equilibration of lung gas with 1% He and 1% SF6, the maneuver consisting of inspiration of a test gas-free mixture at constant rate (VI), a variable time of breath holding, and an expiration at constant rate (VE), was performed. Fractional concentrations of He and SF6, recorded against expired volume, were analyzed in terms of slope of the alveolar plateau (S) and series (Fowler) dead space (VD). In control conditions (VI = 0.5 l/s, VE = 0.1 l/s) S was about 10% of alveolar-to-inspired concentration difference per liter expirate both for He and SF6. Both SHe and SSF6 were inversely related to VI and VE, the relative changes being more pronounced with varying VE. SHe/SSF6 was higher or lower than unity depending on VI and VE. Both SHe and SSF6 decreased with increasing preinspiratory lung volume. Breath holding up to 10 s slightly decreased SHe and SSF6 while SHe/SSF6 was unchanged. The contribution of continuing gas exchange to S assessed from comparative measurements using the reversed (single breath washin) technique ranged from 6 to 23% in the various conditions. The VDHe/VDSF6 ratio was 0.84 and was little affected in the various settings. Results indicate that the substantial alveolar gas inhomogeneity in the dog lung and the mechanism accounting for S are little diffusion dependent. By exclusion sequential filling and emptying of lung units is believed to constitute the most important mechanism responsible for the sloping alveolar plateau.     

Effects of acute exposure to high altitude on ventilatory drive and respiratory pattern

To assess changes in ventilatory regulation in terms of central drive and timing, on exposure to high altitude, and the effects of induced hyperoxia at high altitude, six healthy normal lowland subjects (mean age 19.5 +/- 1.64 yr) were studied at low altitude (518 m) and on the first 4 days at high altitude (3,940 m). The progressive increase in resting expired minute ventilation (VE; control mean 9.94 +/- 1.78 to 14.25 +/- 2.67 l/min on day 3, P less than 0.005) on exposure to high altitude was primarily due to a significant increase in respiratory frequency (f; control mean 15.6 +/- 3.5 breaths/min to 23.8 +/- 6.2 breaths/min on day 3, P less than 0.01) with no significant change in tidal volume (VT). The increase in f was due to significant decreases in both inspiratory (TI) and expiratory (TE) time per breath; the ratio of TI to TE increased significantly (control mean 0.40 +/- 0.08 to 0.57 +/- 0.14, P less than 0.025). Mouth occlusion pressure did not change significantly, nor did the ratio of VE to mouth occlusion pressure. The acute induction of hyperoxia for 10 min at high altitude did not significantly alter VE or the ventilatory pattern. These results indicate that acute exposure to high altitude in normal lowlanders causes an increase in VE primarily by an alteration in central breath timing, with no change in respiratory drive. The acute relief of high altitude hypoxia for 10 min has no effect on the increased VE or ventilatory pattern.     

Automated detection of the phase III slope during inert gas washout testing

We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S(acin) and S(cond), from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A sample set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters. We then applied our technique to a test set of 30 subjects (with an even number of subjects in each of the above groups) and compared these results against the manual analysis of a third independent manual interpreter. Indexes of ventilation heterogeneity were determined using both methods and compared. The phase III slopes determined by the automatic technique best matched the manual interpreter when the phase III slope was calculated from the phase II-III transition point plus the addition of 50% of the phase II volume to the end of the expiration. Calculation of the indexes S(acin) and S(cond) showed no overall difference between analysis methods in either S(acin) (P = 0.14) or S(cond) (P = 0.59) when the set threshold was applied to our automated analysis. Our analysis method provides an alternate means for rapid quantification of the MBNW test, removing operator dependence without alteration in either S(acin) or S(cond).     

Physiological dead space and effective parabronchial ventilation in ducks

Gas exchange in avian lungs is described by a cross-current model that has several differences from the alevolar model of mammalian gas exchange [e.g., end-expired PCO2 greater than arterial PCO2 (PaCO2)]. Consequently the methods available for estimating effective ventilation and physiological dead space (VDphys) in alveolar lungs are not suitable for an analysis of gas exchange in birds. We tested a method for measuring VDphys in birds that is functionally equivalent to the conventional alveolar VDphys. A cross-current O2-CO2 diagram was used to define the ideal expired point (PEi) and VDphys was calculated as from the equation, VDphys = [(PEiCO2--PECO2)/PEiCO2]. VT, where VT is tidal volume. In seven Pekin ducks VDphys was 13.8 ml greater than anatomic dead space and measured changes in the instrument dead space volume. VDphys also reflected changes in ventilation-perfusion inequality induced by temporary unilateral pulmonary arterial occlusion. Bohr dead space, calculated by substituting end-expired PCO2 for PEiCO2, was insensitive to such inhomogeneity. Enghoff dead space, calculated by substituting PaCO2 for PEiCO2, is theoretically incorrect for cross-current gas exchange and was often less than anatomic dead space. We conclude that VDphys is a useful index of avian gas exchange and propose a standard definition for effective parabronchial ventilation (VP) analogous to alveolar ventilation (i.e., VP = VE--VDphys, where VE is total ventilation).     

Model of gas transport during high-frequency ventilation

We analyze gas exchange during high-frequency ventilation (HFV) by a stochastic model that divides the dead space into N compartments in series where each compartment has a volume equal to tidal volume (V). We then divide each of these compartments into alpha subcompartments in series, where each subcompartment receives a well-mixed concentration from one compartment and passes a well-mixed concentration to another in the direction of flow. The number of subcompartments is chosen on the basis that 1/alpha = (sigma t/-t)2, where -t is mean transit time across a compartment of volume, and sigma t is standard deviation of transit times. If (sigma t/-t)D applies to the transit times of the entire dead space, the magnitude of gas exchange is proportional to (sigma t/-t)D, frequency, and V raised to some power greater than unity in the range where V is close to VD. When V is very small in relation to VD, gas exchange is proportional to (sigma t/-t)2D, frequency, and V raised to a power equal to either one or two depending on whether the flow is turbulent or streamline, respectively. (sigma t/-t)D can be determined by the relation between the concentration of alveolar gas at the air outlet and volume expired as in a Fowler measurement of the volume of the dead space.     

Role of ventilation strategy on perfluorochemical evaporation from the lungs.

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.     

Correction of inert gas washin or washout for gas solubility in blood

We show that when an inert gas is washed into the lungs its retention in the blood during any one breath is approximately proportional to its solubility. This relationship makes possible the correction of washin or washout data for blood uptake or release, provided that two gases of different solubility are used simultaneously. The method automatically allows for the characteristics of an individual washin or washout and for the occurrence of recirculation within a fairly short washin or washout period. It has been tested in models with nonuniform ventilation and perfusion and closely approximates the behavior of a truly insoluble gas. In the derived ventilation distribution, gas solubility appears as ventilation to units of low turnover. In the case of N2 this effect is small but causes appreciable overestimation of lung volume. The recovered dead space and main alveolar distribution are insignificantly affected.     

Simultaneous diffusion and convection in single breath lung washout

Two mathematical models of pulmonary single breath gas washout (one analytic, one numerical) are developed and their predictions compared with experimental data on human subjects. Weibel's 23 generation symmetric anatomical model is used as a guide to bronchial tree geometry. Experimental plots of nitrogen concentration versus volume expired, dead space versus breath holding time, and dead space versus tidal volume are compared with plots predicted by the models. Agreement is good. A plot of nitrogen concentration in the airways as predicted by the numerical model at different times during inhalation and exhalation of a single breath of oxygen is shown. Model predictions for changes in dead space with changes in washout gas and expiratory flow rate are discussed. Use of the analytic model for obtaining average values of the path length from mouth to alveoli in a given subject is discussed. To the extent of their agreement with experiment, the models provide a sound physical basis for the correlation of airway structure and function.     

Effect of high-intensity exercise on the VE-VCO2 relationship

The intrinsic relationship between ventilation (VE) and carbon dioxide output (VCO2) is described by the modified alveolar ventilation equation VE = VCO2 k/PaCO2(1-VD/VT) where PaCO2 is the partial pressure of CO2 in the arterial blood and VD/VT is the dead space fraction of the tidal volume. Previous investigators have reported that high-intensity exercise uncouples VE from VCO2; however, they did not measure the PaCO2 and VD/VT components of the overall relationship. In an attempt to provide a more complete analysis of the effects of high-intensity exercise on the VE-VCO2 relationship, we undertook an investigation where five subjects volunteered to perform three steady-state tests (SS1, SS2, SS3) at 60 W. One week after SS1 each subject was required to perform repeated 1-min bouts of exercise corresponding to a work rate of approximately 140% of maximal oxygen uptake (VO2max). Two and 24 h later the subjects performed SS2 and SS3, respectively. This exercise intervention caused PaCO2 during SS2 and SS3 to be regulated (P less than 0.01) approximately 4 Torr below the control (SS1) value of 38.8 Torr. Additionally, significant alterations were noted for VCO2 with corresponding values of 1.15 (SS1), 1.10 (SS2), and 1.04 (SS3) l/min. No changes were noted in either VD/VT or VE. In summary, it seems reasonable to suggest that the disproportionate increase in VE with respect to VCO2 noted in earlier work does not reflect an uncoupling. Rather the slope of the VE-VCO2 relationship is increased in a predictable manner as described by the modified alveolar ventilation equation.     

Respiration in awake cats: sympathectomy and deafferentation of carotid bifurcations

Respiratory effects of sympathectomy of the carotid bifurcations and, in a subsequent experiment, bilateral carotid sinus nerve section were examined in six awake resting cats. In each intact and denervated state, sequential breaths were analyzed at 10-min intervals up to 80 min. Individual breath frequency (f), tidal volume (VT), and ventilation (V = f X VT) were determined. In individual cats, sympathectomy or deafferentation could cause significant increases or decreases in ventilation or no change. Thus the range of spontaneous variability in breath V as well as minute ventilation (VE), averaged for the group, were not consistently altered in the same direction by either sympathectomy or deafferentation of the carotid bifurcations. Interestingly, in most cats after both sympathectomy (5 of 6) and deafferentation (4 of 6), VT increased and f decreased relative to V. Despite this, after sinus nerve section in two cats arterial PO2 decreased and arterial PCO2 tended to increase relative to VE, suggesting possible effects of deafferentation on ventilation-perfusion balance. Sympathectomy also affected timing such that inspiratory time began to exceed 0.5 of the breath duration at a lower breath f; this effect of sympathectomy was reversed to intact values by subsequent sinus deafferentation. Thus, in eupneic awake cats, sympathetics normally suppress reflex modulation of central timing from carotid chemoreceptors and/or baroreceptors.     

Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men.

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DL(NO)) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O(2) consumption of 1.3 +/- 0.2 l/min (mean +/- SD). DL(NO) was 202.7 +/- 71.2 ml. min(-1). Torr(-1) and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO(2), mixed expired CO(2), and mixed expired CO, was 46.9 +/- 12.8 ml. min(-1). Torr(-1). NO dead space = (VT x FE(NO) - VT x FA(NO))/(FI(NO) - FA(NO)) = 209 +/- 88 ml, where VT is tidal volume and FE(NO), FI(NO), and FA(NO) are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO(2) dead space from mixed exhaled and end-tidal (assumed alveolar) CO(2) = 430 +/- 136 ml. Predicted anatomic dead space = 199 +/- 22 ml. Membrane diffusing capacity was 333 and 166 ml. min(-1). Torr(-1) for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DL(NO) at the concentrations used.     

Effects of almitrine on respiration in unanesthetized newborn rabbits

We previously demonstrated that almitrine, a peripheral chemoreceptor stimulant, increased tidal volume (VT), expired minute ventilation (VE), and respiratory frequency (f) and decreased inspiratory (TI) and expiratory time (TE) in sleeping adult cats. We now hypothesized that almitrine would induce an increase in ventilation in a young animal model. Respiration was studied by the barometric method in 11 unanesthetized New Zealand White rabbit pups between 3 and 6 days of age. Recordings were made in 0.21 FIO2 at base line and after cumulative intraperitoneal infusions of almitrine (2.5, 5.0, and 7.5 mg/kg). The chamber pressure deflection (proportional to VT after appropriate calculation) was computer sampled at 200 Hz. At least 100 breaths for each dose in each animal were analyzed. We found that a 7.5-mg/kg intraperitoneal dose of almitrine increased f to 135 +/- 9% (SE) of base line and decreased TE and TI to 72 +/- 8% and 79 +/- 8% of base line, respectively. Changes in VE, VT/TI, and VT were not significant. Recognizing that apnea is associated with inadequate ventilation and a prolonged TE (failure of the "inspiratory on-switch"), these results, particularly the increase in f and decrease in TE, suggest that almitrine might be useful in treating apnea in preterm infants.     

An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.