Oronasal partitioning of ventilation during exercise in humans

The partitioning of oronasal breathing was studied in five normal subjects during progressive exercise. Subjects performed three to five identical runs, each consisting of four 1-min work periods at increments of 50 W. Nasal and oral airflow were measured simultaneously using a partitioned face mask both during and for 4 min after exercise. Total mean flows were the sum of nasal and oral flows. At a total mean inspiratory flow of 2 l/s, the nasal fraction of total flow was 0.36 +/- 0.04 (SE) and decreased by 6 +/- 3% between total flows of 1.5 and 2.5 l/s. Throughout exercise, the nasal fraction of total mean inspiratory flow did not differ from that of total expiratory flow and was similar to that of total mean inspiratory flow during the postexercise period at a corresponding total mean flow (both P greater than 0.02). The results show that oronasal flow partitioning is not directly due to the exercise itself but is related to the level of ventilation and is uninfluenced by the direction of upper airway flow (i.e., inspiratory vs. expiratory). These findings suggest tightly controlled modulation of the relative resistances of the oral and/or nasal pathways.     

Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal human lung

Amodel integrating airway/lung mechanics, pulmonary blood flow, and gasexchange for a normal human subject executing the forced vital capacity(FVC) maneuver is presented. It requires as input the intrapleuralpressure measured during the maneuver. Selected model-generated outputvariables are compared against measured data (flow at the mouth, changein lung volume, and expired O₂ and CO₂concentrations at the mouth). A nonlinear parameter-estimation algorithm is employed to vary selected sensitive model parameters toobtain reasonable least squares fits to the data. This study indicatesthat 1) all three components of the respiratory model arenecessary to characterize the FVC maneuver; 2) changes in pulmonary blood flow rate are associated with changes in alveolar andintrapleural pressures and affect gas exchange and the time course ofexpired gas concentrations; and 3) a collapsible midairway segment must be included to match airflow during a forced expiration. Model simulations suggest that the resistances to airflow offered bythe collapsible segment and the small airways are significant throughout forced expiration; their combined effect is needed toadequately match the inspiratory and expiratory flow-volume loops.Despite the limitations of this lumped single-compartment model, aremarkable agreement with airflow and expired gas concentration measurements is obtained for normal subjects. Furthermore, the modelprovides insight into the important dynamic interactions betweenventilation and perfusion during the FVC maneuver.

     

Convective exchange between the nose and the atmosphere

It is generally accepted that there is little rebreathing of gas exhaled through the nose. A detailed physical model system has been used to quantify and identify the mechanisms responsible for this phenomenon. By the use of a cast of the upper respiratory tract and oscillating flows with a Reynolds number of 500 and nondimensional frequency of 1.6, corresponding to quiet tidal breathing through the nose, dye dilution measurements indicated an efficiency of tidal exchange of 0.95. Flow visualization studies performed to trace the expiratory flow, as well as the streamlines during steady inspiratory flow, support the hypothesis that the high efficiency of exchange is due to radical differences in the velocity fields between inspiratory and expiratory phases of this oscillatory flow. These findings confirm that convective gas exchange between the nose and the atmosphere is highly efficient; however, the underlying mechanism responsible for this exchange also maximizes the exposure of the respiratory system to aerosols contained in the ambient atmosphere.     

Modelling the respiratory airflow pattern by optimization criteria

A model of the control of the respiratory cycle pattern is presented in which the airflow shape is determined by a dynamic optimization problem. The inspiratory and expiratory phases have different performance criteria both of which are related to the oxygen cost of breathing, and to the minimization of tissue damage and control difficulties. The model successfully predicts various patterns of spontaneous breathing during both inspiration and expiration. The effects of applying elastic and resistive loads to the respiratory system can also be predicted. The model performance is in good agreement with the experimental observation that increasing resistance makes the airflow patterns more rectangular.     

Respiratory effects of transient axial acceleration.

Whereas gravity has an inspiratory effect in upright subjects, transient upward acceleration is reported to have an expiratory effect. To explore the respiratory effects of transient axial accelerations, we measured axial acceleration at the head and transrespiratory pressure or airflow in five subjects as they were dropped or lifted on a platform. For the first 100 ms, upward acceleration caused a decrease in mouth pressure and inspiratory flow, and downward acceleration caused the opposite. We also simulated these experimental observations by using a computational model of a passive respiratory system based on anatomical data and normal respiratory characteristics. After 100 ms, respiratory airflow in our subjects became highly variable, no longer varying with acceleration. Electromyograms of thoracic and abdominal respiratory muscles showed bursts of activity beginning 40-125 ms after acceleration, suggesting reflex responses responsible for subsequent flow variability. We conclude that, in relaxed subjects, transient upward axial acceleration causes inspiratory airflow and downward acceleration causes expiratory airflow, but that after ~100 ms, reflex activation of respiratory musculature largely determines airflow.     

Analysis of the behavior of the respiratory system with constant inspiratory flow

For a respiratory system with constant compliance and resistance a constant flow can occur during part or all of inspiration in two situations: when the flow is constrained to be constant throughout inspiration, such as is the case with some mechanical ventilators, and when the applied pressure is a ramp (i.e., increasing constantly with time), which may occur during mechanical ventilation and spontaneous breathing. After initial transients in pressure and flow, respectively, have decayed away both situations result in linear volume-time and pressure-time relationships. The slope of the corresponding pressure-volume line then yields an estimate of the total compliance of the respiratory system, and the intercept, divided by the constant flow, provides the total resistance. We have shown theoretically that, for a model composed of two compartments in parallel, the total compliance is the same as the static compliance and equals the sum of the compliances of the two compartments. Furthermore, this compliance is independent of the breathing frequency. However, the total resistance is, in general, a function of both the resistances and the compliances. When the time constants of the two compartments are equal the total resistance assumes its minimum value and becomes independent of the compliances. This minimum value of resistance can be obtained, regardless of the time constants, by dividing the immediate drop in airway opening pressure, obtained after occluding during steady state inspiration, by the inspiratory flow.     

Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia

The interactive effects of upper airway negative pressure and hypercapnia on the pattern of breathing were assessed in pentobarbital-anesthetized cats. At any given level of pressure in the upper airway, hypercapnia increased respiratory rate, reduced inspiratory time, and augmented tidal volume, inspiratory airflow, and the peak and rate of rise of diaphragm electrical activity. Conversely, at any given level of CO2, upper airway negative pressure decreased respiratory rate, prolonged inspiratory time, and depressed inspiratory airflow and diaphragm electromyogram (EMG) rate of rise. Application of negative pressure to the upper airway shifted the relationship between tidal volume and inspiratory time upward and rightward. The relationship between inspiratory and expiratory times, however, was linearly correlated over a wide range of chemical drives and levels of upper airway pressure. These results suggest that in the anesthetized cat upper airway negative pressure afferent inputs 1) interact in an additive fashion with hypercapnia to alter the pattern of breathing, 2) interact multiplicatively with CO2 to influence mean inspiratory airflow and diaphragm EMG rate of rise, 3) depress the generation of central inspiratory activity, 4) increase the time-dependent volume threshold for inspiratory termination, and 5) affect the ratio between inspiratory and expiratory times in a similar manner as alterations in PCO2.     

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Sleep is associated with marked alterations in ventilatory control that lead to perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer powerful insight into the pathogenesis of SRBD; however, methods for obtaining the full complement of continuous, high-fidelity respiratory, electroencephalographic (EEG), and electromyographic (EMG) signals in unrestrained mice during sleep and wake have not been developed. We adapted whole body plethysmography to record EEG, EMG, and respiratory signals continuously in unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and airflow signals and a novel noninvasive surrogate for respiratory effort (respiratory movement signal) were validated against simultaneously measured gold standard signals. Compared with the gold standard, we validated 1) tidal volume (correlation, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R(2) = 0.79-0.84, P < 0.001). The expiratory airflow signal, however, demonstrated a decrease in amplitude compared with the gold standard. Integrating respiratory and EEG/EMG signals, we fully characterized sleep and breathing patterns in conscious, unrestrained mice and demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our approach will facilitate studies of SRBD mechanisms in inbred mouse strains and offer a powerful platform to investigate the effects of environmental and pharmacological exposures on breathing disturbances during sleep and wakefulness.     

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.     

Steady pressure-flow relationship in a cast of the upper and central human airways

Pressure drops across the upper (larynx) and central airways of a human lung cast were measured at steady state inspiratory and expiratory flows. Air, HeO₂ and SF6-O₁ gas mixtures were used at tracheal Reynolds' numbers ranging from 145 to 30 000. The pressure-flow characteristics of the model were analysed using standard pressure-flow diagrams and Moody plots. We found that the asymmetry between inspiratory and expiratory resistances, observed in the central airways (larynx excluded), was markedly reduced in the presence of the larynx. However, static pressure differences were greater across the entire model of the upper and central airways than across the model of the five generations of the tracheo-bronchial tree (without larynx) at the same flow-rates. In addition, our results showed that the presence of the larynx tended to reduce the zone of fully developed laminar flow in the Moody diagram with the higher density gas, while extending the zone of turbulent flow even for the low density gas at low Reynold's numbers.     

Integrated approach for in vivo evaluation of respiratory muscles mechanics

The respiratory muscles constitute the respiratory pump, which determines the efficacy of ventilation. Any functional disorder in their performance may cause insufficient ventilation. This study was designed to quantitatively explore the relative contribution of major groups of respiratory muscles to global lung ventilation throughout a range of maneuvers in healthy subjects. A computerized experimental system was developed for simultaneous noninvasive measurement of inspired/expired airflow, mouth pressure and up to 8 channels of EMG surface signals from major respiratory muscles which are located near the skin (e.g., sternomastoid, external intercostal, rectus abdominis and external oblique) during various respiratory maneuvers. Lung volumes values were calculated by integration of airflow data. Hill's muscle model was utilized to calculate the forces generated by the muscles from the acquired EMG data. Analysis of EMG measurements and respiratory muscles forces revealed the following characteristics: (a) muscle activity increased with increased breathing effort, (b) inspiratory muscles contributed to inspiration even at relatively low flow rates, while expiratory muscles are recruited at higher flow rates, (c) the forces generated by the muscle depended on the muscle properties as well as on their EMG performance and (d) the pattern of the muscle's force curves varied between subjects, but were generally consistent for the same subject regardless of breathing effort.     

Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography.

Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air (n = 12) or in 100% oxygen for 24 (n = 9), 48 (n = 8), or 60 (n = 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system.     

Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.     

Mucus clearance by two-phase gas-liquid flow mechanism: asymmetric periodic flow model

Mucus transport by two-phase gas-liquid flow mechanism was investigated with in vitro flow models under asymmetric periodic airflow conditions with nine different liquid solutions with rheological properties similar to human sputum. The flow model was made with 1.0-cm-ID glass tube and positioned either vertically or horizontally. With a constant supply of the test liquids into the model tube (0.5 ml/min), the liquid layer transport speed (LLTS) as well as the mean liquid layer thickness at steady-state condition (hs) was measured in conjunction with various airflow patterns of different expiratory and inspiratory flow rate, breathing frequency (f), and tidal volume (VT). The flow patterns were maintained within the range of normal breathing. In the horizontal tube model, LLTS ranged from 1.14 +/- 0.02 to 3.39 +/- 0.04 cm/min at the peak expiratory flow rate (VEp) of 30-60 l/min. The inspiratory flow rate, as well as f and VT did not affect LLTS. However, LLTS increased with increasing VEp, and at the same VEp LLTS was higher with viscoelastic than with viscous liquid. In the vertical tube model, the upward transport of mucus could not be achieved at VEp lower than 30 l/min particularly with low viscosity and low elasticity fluid. However, at high values of VEp, LLTS was comparable to that in the horizontal tube model with viscoelastic fluid, whereas LLTS of viscous liquid showed 26-40% lower than that in the horizontal tube model. The value of hs was 5-20% of the tube diameter at VEp of 30-60 l/min in both models. These results indicate that effective mucus clearance can be achieved by two-phase gas-liquid flow mechanism in patients with excessive bronchial secretions with biased tidal breathing favoring the expiratory flow and that the clearance can be further promoted by changing rheological properties of mucus.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Effects of PGF2 alpha on the EMG of costal and crural parts of the diaphragm of the newborn pig

We investigated the effects of PGF2 alpha on the breathing patterns and electric activity of costal and crural parts of the diaphragm in 9 anesthetized newborn pigs. The change in diaphragmatic tension was evaluated as the change in transdiaphragmatic pressure. Because PGF2 alpha induces bronchoconstriction and an increase in respiratory resistances, the changes induced by prostaglandin were evaluated as differences between bronchoconstriction after PGF2 alpha and resistive load obtained by applying gradual occlusion to the inspiratory line of the breathing circuit. Our results show that PGF2 alpha decreased respiratory frequency with lengthening of expiratory time, while the resistive load increased both respiratory phases. The changes in breathing pattern were associated with different electrical activities of the diaphragm. While resistive load did not significantly change the EMG power spectrum, PGF2 alpha recruited new motor units. Furthermore, resistive load induced synchronization of the inspiratory time discharge of the costal and crural parts of the diaphragm, while after PGF2 alpha infusion there was an early inspiratory discharge of the crural part.     

Some recent advances on the study and understanding of the functional design of the avian lung: morphological and morphometric perspectives

The small highly aerobic avian species have morphometrically superior lungs while the large flightless ones have less well-refined lungs. Two parabronchial systems, i.e. the paleopulmo and neopulmo, occur in the lungs of relatively advanced birds. Although their evolution and development are not clear, understanding their presence is physiologically important particularly since the air- and blood flow patterns in them are different. Geometrically, the bulk air flow in the parabronchial lumen, i.e. in the longitudinal direction, and the flow of deoxygenated blood from the periphery, i.e. in a centripetal direction, are perpendicularly arranged to produce a cross-current relationship. Functionally, the blood capillaries in the avian lung constitute a multicapillary serial arterialization system. The amount of oxygen and carbon dioxide exchanged arises from many modest transactions that occur where air- and blood capillaries interface along the parabronchial lengths, an additive process that greatly enhances the respiratory efficiency. In some species of birds, an epithelial tumescence occurs at the terminal part of the extrapulmonary primary bronchi (EPPB). The swelling narrows the EPPB, conceivably allowing the shunting of inspired air across the openings of the medioventral secondary bronchi, i.e. inspiratory aerodynamic valving. The defence stratagems in the avian lung differ from those of mammals: fewer surface (free) macrophages (SMs) occur, the epithelial cells that line the atria and infundibula are phagocytic, a large population of subepithelial macrophages is present and pulmonary intravascular macrophages exist. This complex defence inventory may explain the paucity of SMs in the avian lung.     

Pneumotachograph calibration for inspiratory and expiratory flows during HeO2 breathing

Maximum expiratory flows during breathing of a 80% helium-20% oxygen mixture (HeO2) are commonly used to determine the site of airflow limitation. To do this test the flowmeter is usually calibrated with the inspired gases, and the airflows are measured during expiration. We tested the adequacy of such calibration maneuvers by using two identical flowmeters in series through a bag-in-box system. Different gases were flowed though the test pneumotachograph into a bag contained in a closed box connected to the second pneumotachograph. Distension of the bag caused air to flow from the box through this second pneumotachograph. Our results indicate that when breathing HeO2, the flowmeter correction for different gas viscosity, compared with air, should be 20% for inspired HeO2 and 12% for expired gases. Inspired gases therefore cannot be used to calibrate the flowmeters when assessing expiratory flows.     

Nasal resistance and flow resistive work of nasal breathing during exercise: effects of a nasal dilator strip.

Using posterior rhinomanometry, we measured nasal airflow resistance (Rn) and flow-resistive work of nasal breathing (WONB), with an external nasal dilator strip (ENDS) and without (control), in 15 healthy adults (6 men, 9 women) during exclusive nasal breathing and graded (50-230 W) exercise on a cycle ergometer. ENDS decreased resting inspiratory and/or expiratory Rn (at 0.4 l/s) by >0.5 cmH(2)O. l(-1). s in 11 subjects ("responders"). Inspired ventilation (VI) increased with external work rate, but tended to be greater with ENDS. Inspiratory and expiratory Rn (at 0.4 l/s) decreased as VI increased but, in responders, tended to remain lower with ENDS. Inspiratory (but not expiratory) Rn at peak nasal airflow (Vn) increased as VI increased but, again, was lower with ENDS. At a VI of approximately 35 l/min, ENDS decreased flow limitation and hysteresis of the inspiratory transnasal pressure-flow curve. In responders, ENDS reduced inspiratory WONB per breath and inspiratory nasal power values during exercise. We conclude that ENDS stiffens the lateral nasal vestibule walls and, in responders, may reduce the energy required for nasal ventilation during exercise.