High-frequency oscillations via the pleural surface: an alternative mode of ventilation?

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5-40 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.     

Flow and volume dependence of respiratory mechanical properties studied by forced oscillation

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.     

Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory effects of the Jarvik-7 artificial heart

In five anesthetized patients with a Jarvik-7 artificial heart, pulmonary volume displacements generated by cardiogenic oscillations were measured using an indirect spirometric method. Consequences on gas exchange were also evaluated during a 15-min period of apnea by use of a tracheal insufflation of pure O2 at a constant flow rate of 20 l/min. The Jarvik-7 artificial heart generated a mean pulmonary volume displacement of 105 +/- 29 (SD) ml/heart beat. After 15 min of apnea, arterial PCO2 (PaCO2) significantly increased from 29 +/- 5 to 47 +/- 6 (SD) Torr. PaCO2 increased by 0.8 Torr/min from the 5th to the 15th min of apnea. Mean arterial PO2, mean pulmonary shunt, mean O2 consumption, and mean metabolic production of CO2 did not change significantly during the apnea period. Because cardiac output was kept constant during the study, O2 transport was adequately maintained throughout the apnea period. In patient 1, where the period of apnea was continued for 60 min, PaCO2 progressively increased until the 45th min and then remained stable at 61 Torr during the last 15 min of apnea. This "plateau" corresponded to an alveolar ventilation of 3,907 ml/min, representing 69% of the alveolar ventilation calculated during conventional mechanical ventilation. In conclusion, the Jarvik-7 artificial heart provides a potent respiratory support through the cardiogenic oscillations it generates.     

Arteriovenous extracorporeal lung assist allows for maximization of oscillatory frequencies: a large-animal model of respiratory distress

Background

Although the minimization of the applied tidal volume (VT) during high-frequency oscillatory ventilation (HFOV) reduces the risk of alveolar shear stress, it can also result in insufficient CO₂-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS) the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA) in order to maintain or reestablish normocapnia.

Methods

After induction of ARDS in eight female pigs (56.5 ± 4.4 kg), a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw) was adjusted 3 cmH₂O above the lower inflection point (Plow) of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3–15 Hz. The pressure amplitude was fixed at 60 cmH₂O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia.

Results

Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p < 0.05). Compared to lung injury, oxygenation remained significantly improved with rising frequencies (p < 0.05). Normocapnia during HFOV was only maintained with the addition of av-ECLA during frequencies of 9 Hz and above.

Conclusion

In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation     

Lung and chest wall impedances in the dog: effects of frequency and tidal volume.

Dependences of the mechanical properties of the respiratory system on frequency (f) and tidal volume (VT) in the normal ranges of breathing are not clear. We measured, simultaneously and in vivo, resistance and elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) of five healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50-300 ml, 0.2-2 Hz) delivered at a constant mean lung volume. Each dog showed the same f and VT dependences. The Ers and Ecw increased with increasing f to 1 Hz and decreased with increasing VT up to 200 ml. Although EL increased slightly with increasing f, it was independent of VT. The Rcw decreased from 0.2 to 2 Hz at all VT and decreased with increasing VT. Although the RL decreased from 0.2 to 0.6 Hz and was independent of VT, at higher f RL tended to increase with increasing f and VT (i.e., as peak flow increased). Finally, the f and VT dependences of Rrs were similar to those of Rcw below 0.6 Hz but mirrored RL at higher f. These data capture the competing influences of airflow nonlinearities vs. tissue nonlinearities on f and VT dependence of the lung, chest wall, and total respiratory system. More specifically, we conclude that 1) VT dependences in Ers and Rrs below 0.6 Hz are due to nonlinearities in chest wall properties, 2) above 0.6 Hz, the flow dependence of airways resistance dominates RL and Rrs, and 3) lung tissue behavior is linear in the normal range of breathing.     

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.     

Photographic measurement of pleural surface motion during lung oscillation

The regional pleural surface expansion of an excised dog lung was measured during high-frequency ventilation (HFV) using synchronized stroboscopic photography to stop lung motion at 20 evenly spaced intervals over a respiratory cycle during ventilation at 1 Hz with a volume of 100 ml, 15 Hz with 100 ml, or 30 Hz with 50 ml. The lungs were also photographed during quasi-static deflation. The pleural surface was marked with ink dots to form 84 approximately square figures. The side lengths and areas of each of the 84 "squares" were measured for each frame of each photo sequence. At 1 Hz and during the quasi-static deflation the lung ventilated nearly synchronously, although minor nonuniformities were noted on both small and large length scales. At 15 and 30 Hz, the lung expanded asynchronously and nonuniformly, with a 78% increase in surface expansion per 100 ml of tracheal tidal volume, as frequency was increased from 1 to 30 Hz. These nonuniformities in expansion suggest marked interregional airflow and elastic wave propagation in the parenchyma during HFV.     

Respiratory input impedance in anesthetized paralyzed patients

Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube. Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz. From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz. Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz. Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz. We interpreted Zrs data in terms of a T network mechanical model. We represented the proximal branch by central airway resistance and inertance. The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility. The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues. When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al. (J. Appl. Physiol. 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated. The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity. Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties.     

Ventilation by external high-frequency oscillation in cats

Eight anesthetized tracheostomized cats were placed in an 8.2-liter airtight chamber with the trachea connected to the exterior. Thirty-two combinations of high-frequency oscillations (HFO) (0.5-30 Hz; 25-100 ml) were delivered for 10 min each in random order into the chamber. Arterial blood gas tensions during oscillation were compared with control measurements made after 10 min of spontaneous breathing without oscillation when the mean arterial PCO2 (PaCO2) was 30.1 Torr. Ventilation due to spontaneous breathing (Vs) and oscillation (Vo) were derived from the chamber pressure trace and a pneumotachograph, respectively. As the oscillation frequency increased, oscillated tidal volume (Vo) decreased from a mean of 39 (0.5 Hz) to 3.3 ml (30 Hz) when 100 ml was delivered to the chamber. From 6-25 Hz, apnea occurred with Vo less than estimated respiratory dead space (VD); the minimum effective Vo/VD ratio was 0.37 +/- 0.05. Although Vo was maximal at 10 Hz at each oscillation volume, the lowest PaCO2 occurred at 2-6 Hz, and arterial PO2 rose as expected during hypocapnia. Above 10 Hz, PaCO2 was determined by Vo and was independent of frequency, whereas at lower frequencies, PaCO2 was related to Vo; below 6 Hz, PaCO2 varied inversely with the calculated alveolar ventilation. As oscillations became more effective, both PaCO2 and Vs fell progressively and were highly correlated; apnea occurred when PaCO2 was reduced by a mean of 4.5 Torr. Mean chamber pressure remained near zero up to 15 Hz, indicating functional residual capacity did not change. We conclude that externally applied HFO can readily maintain gas exchange in vivo, with Vo less than VD at frequencies over 2 Hz.     

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.     

Augmentation of respiratory sinus arrhythmia in response to progressive hypercapnia in conscious dogs

Respiratory sinus arrhythmia (RSA) may serve to enhance pulmonary gas exchange efficiency by matching pulmonary blood flow with lung volume within each respiratory cycle. We examined the hypothesis that RSA is augmented as an active physiological response to hypercapnia. We measured electrocardiograms and arterial blood pressure during progressive hypercapnia in conscious dogs that were prepared with a permanent tracheostomy and an implanted blood pressure telemetry unit. The intensity of RSA was assessed continuously as the amplitude of respiratory fluctuation of heart rate using complex demodulation. In a total of 39 runs of hypercapnia in 3 dogs, RSA increased by 38 and 43% of the control level when minute ventilation reached 10 and 15 l/min, respectively (P < 0.0001 for both), and heart rate and mean arterial pressure showed no significant change. The increases in RSA were significant even after adjustment for the effects of increased tidal volume, respiratory rate, and respiratory fluctuation of arterial blood pressure (P < 0.001). These observations indicate that increased RSA during hypercapnia is not the consequence of altered autonomic balance or respiratory patterns and support the hypothesis that RSA is augmented as an active physiological response to hypercapnia.     

A model evaluation of estimates of breath-to-breath alveolar gas exchange

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.     

Total and local impedances of the chest wall up to 10 Hz

To understand how bical mechanical chest wall (CW) properties are related to those of the CW as a whole, we measured esophageal and gastric pressures, CW volume changes (measured with a head-out body plethysmograph), and anteroposterior and transverse CW diameter changes (measured with magnetometers attached to the surface) during sinusoidal forcing at the mouth (2.5% vital capacity, 0.5-10 Hz) in four healthy subjects. Total CW resistance decreased sharply as frequency rose to 3-4 Hz and remained relatively constant at higher frequencies. Total CW reactance became less negative with increasing frequency but showed no tendency to change sign. Above 2 Hz, diameters measured at different locations changed asynchronously between and within the rib cage and abdomen. "Local pathway impedances" (ratios of esophageal or gastric pressure to a rate of diameter change) showed frequency dependence similar to that of the total CW less than 3 Hz. Local pathway impedances increased during contraction of respiratory muscles acting on the pathway. We conclude that 1) total CW behavior is mainly a reflection of its individual local properties at less than or equal to 3 Hz, 2) local impedances within the rib cage or within the abdomen can change independently in some situations, and 3) asynchronies that develop within the CW during forcing greater than 3 Hz suggest that two compartments may be insufficient to describe CW properties from impedance measurements.     

Measurement of tidal lung volumes in neonates during high-frequency oscillation

High-frequency oscillation (HFO) has been used clinically to ventilate infants with respiratory distress. However, there are problems in monitoring the effects on the respiratory system and in particular in measuring the volumes delivered; this is important information in terms of safety and mechanisms of action of HFO. We have validated two sizes of respiratory jacket for measuring oscillatory volume changes of 0.25–5 ml at frequencies of 2–25 Hz, the volume delivered from a purpose-built oscillator having first been validated. Different combinations of volume and frequencies were then oscillated into each jacket, while it was being worn by a well preterm baby. Studies were performed with each jacket on five babies with weights between 0.82 and 1.86 kg. The results showed that at any given frequency there was a linear relationship between the pressure oscillations measured from a side port of the jacket and the delivered volume. Both jackets showed the same pattern of frequency response, overreading at < 10 Hz and underreading at 10–25 Hz. When appropriately calibrated, the respiratory jacket can be used as a non-invasive method of measuring volumes delivered by HFO.     

Measurement of thoracic gas volume by low-frequency ambient pressure changes

When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.     

Human respiratory input impedance between 32and 800Hz, measured by interrupter technique and forced oscillations

Frey, Urs, Bela Suki, Richard Kraemer, and Andrew C. Jackson. Human respiratory input impedance between 32 and 800 Hz,measured by interrupter technique and forced oscillations. J. Appl. Physiol. 82(3):1018-1023, 1997.Respiratory input impedance (Zin) over a widerange of frequencies (f) has beenshown to be useful in determining airway resistance (Raw) and tissueresistance in dogs or airway wall properties in human adults. Zinmeasurements are noninvasive and, therefore, potentially useful ininvestigation of airway mechanics in infants. However, accuratemeasurements of Zin at these f valueswith the use of forced oscillatory techniques (FOT) in infants aredifficult because of their relatively high Raw and large compliance ofthe face mask. If pseudorandom noise pressure oscillations generated bya loudspeaker are applied at the airway opening (FOT), the power of theresulting flow decreases inversely withf because of capacitive shunting intothe volume of the gas in the speaker chamber and in the face mask. Westudied whether high-frequency respiratory Zin can be measured by using rapid flow interruption [high-speed interrupter technique(HIT)], in which we expect the flow amplitude in the respiratorysystem to be higher than in the FOT. We compared Zin measured by HIT with Zin measured by FOT in a dried dog lung and in five healthy adultsubjects. The impedance was calculated from two pressure signalsmeasured between the mouth and the HIT valve. The impedance could beassessed from 32 to 800 Hz. Its real part at lowf as well as thef and amplitude of the first andsecond acoustic resonance, measured by FOT and by HIT, were notsignificantly different. The power spectrum of oscillatory flow whenthe HIT was used showed amplitudes that were at least 100 times greaterthan those when FOT was used, increasing atf > 400 Hz. In conclusion,the HIT enables the measurement of high-frequency Zin data ranging from 32 to 800 Hz with particularly high flow amplitudes and, therefore, possibly better signal-to-noise ratio. This is particularly important in systems with high Raw, e.g., in infants, when measurements have tobe performed through a face mask.

     

Effect of hypoxia on respiratory system impedance in dogs

Simon, B. A., P. B. Zanaboni, and D. P. Nyhan. Effectof hypoxia on respiratory system impedance in dogs. J. Appl. Physiol. 83(2): 451-458, 1997.The effects of hypoxia on lung and airwaymechanics remain controversial, possibly because of the confoundingeffects of competing reflexes caused by systemic hypoxemia. We comparedthe effects of systemic hypoxemia with those of unilateral alveolarhypoxia (with systemic normoxemia) on unilateral respiratory systemimpedance (Z) in intact, anesthetized dogs. Independent lungventilation was obtained with a Kottmeier endobronchial tube.Individual left and right respiratory system Z was measured duringsinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1Hz during control [100% inspiredO₂ fraction(FI_O2)], systemichypoxemia (10% FI_O2), andunilateral alveolar hypoxia (0%FI_O2 to left lung, 100%FI_O2 to right lung). Duringsystemic hypoxemia, there was a mean Z magnitude increase of 18%. Thischange was entirely attributable to a decrease in the imaginarycomponent of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Zwith systemic hypoxemia. In contrast, there was no change in Z in thelung subjected to unilateral alveolar hypoxia. We conclude thatalveolar hypoxia has no direct effect on lung mechanical properties inintact dogs. In contrast, systemic hypoxemia does increase lungimpedance, apparently through a noncholinergic mechanism.

     

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.     

High density respiratory syndrome: II. The mechanics of forced respiration with artificial resistive load under normobaric pressure]

The dynamics of forced inhale (I series) and exhale (II series) parameters with additional external artificial resistive load was studied under normobaric conditions. The artificial resistance to breathing increased stepwise using removable diaphragms with sequential decrease of hole diameter from 25, 17, 13, 9, 7.5, 4.5 to 3 mm. While studying forced inhale the diaphragms were set up at Fleish pipe airflow input. In the case of forced inhale the diaphragms were set up at the pipe output. A phenomenon is revealed which consists in appearance of respiratory flow oscillations on the "flow-volume" curves during forced breathing with an increase of resistive load. Frequency maxima of the oscillations were located within the range of 6-15 Hz. The possible mechanisms for appearance of respiratory muscle tremor and respiratory flow oscillations are under discussion.