Lung pressures and gas transport during high-frequency airway and chest wall oscillation

The major goal of this study was to compare gas exchange, tidal volume (VT), and dynamic lung pressures resulting from high-frequency airway oscillation (HFAO) with the corresponding effects in high-frequency chest wall oscillation (HFCWO). Eight anesthetized paralyzed dogs were maintained eucapnic with HFAO and HFCWO at frequencies ranging from 1 to 16 Hz in the former and 0.5 to 8 Hz in the latter. Tracheal (delta Ptr) and esophageal (delta Pes) pressure swings, VT, and arterial blood gases were measured in addition to respiratory impedance and static pressure-volume curves. Mean positive pressure (25-30 cmH2O) in the chest cuff associated with HFCWO generation decreased lung volume by approximately 200 ml and increased pulmonary impedance significantly. Aside from this decrease in functional residual capacity (FRC), no change in lung volume occurred as a result of dynamic factors during the course of HFCWO application. With HFAO, a small degree of hyperinflation occurred only at 16 Hz. Arterial PO2 decreased by 5 Torr on average during HFCWO. VT decreased with increasing frequency in both cases, but VT during HFCWO was smaller over the range of frequencies compared with HFAO. delta Pes and delta Ptr between 1 and 8 Hz were lower than the corresponding pressure swings obtained with conventional mechanical ventilation (CMV) applied at 0.25 Hz. delta Pes was minimized at 1 Hz during HFCWO; however, delta Ptr decreased continuously with decreasing frequency and, below 2 Hz, became progressively smaller than the corresponding values obtained with HFAO and CMV.     

Alveolar pressure nonhomogeneity during small-amplitude high-frequency oscillation

In six excised canine lungs, regional alveolar pressures (PA) were measured during small-amplitude high-frequency oscillations applied at the airway opening. Both the regional distribution of PA's and their relationship to pressure excursions at the airway opening (Pao) were assessed in terms of amplitude and phase. PA was sampled in several capsules glued to the pleural surface and communicating with alveolar gas via pleural punctures. Pao and PA were measured over the frequency (f) range 1-60 Hz, at transpulmonary pressures (PL) of 5, 10, and 25 cmH2O. The amplitude of PA excursions substantially exceeded Pao excursions at frequencies near the resonant frequency. At resonance the ratio [PA/Pao] was 1.9, 2.9, and 4.8 at PL's of 5, 10, and 25 cmH2O, respectively. Both spatial homogeneity and temporal synchrony of PA's between sampled lung regions decreased with f and increased with PL. Interregional variability of airway impedance [(Pao - PA)/Vao] and tissue impedance (PA/Vao) tended to be larger than differences due to changing PL but not as large as between-dog variability. These data define the baseline nonhomogeneity of the normal canine lung and also suggest that there may be some advantage in applying high-frequency ventilation at frequencies at least as high as lung resonant frequency.     

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)     

Airway pressures in an asymmetrically branched airway model of the dog respiratory system

A computer model of the mechanical properties of the dog respiratory system based on the asymmetrically branching airway model of Horsfield et al. (11) is described. The peripheral ends of this airway model were terminated by a lumped-parameter impedance representing gas compression in the alveoli, and lung and chest wall tissue properties were derived from measurements made in this laboratory. Using this model we predicted the respiratory system impedance and the distribution of pressures along the airways in the dog lung. Predicted total respiratory system impedances for frequencies between 4 and 64 Hz at three lung volumes were found to compare quite closely to measured impedances in dogs. Serial pressure distributions were found to be frequency-dependent and to result in higher pressures in the lung periphery than at the airway opening at some frequencies. The implications of this finding for high-frequency ventilation are discussed.     

Regional mapping of gas transport during high-frequency and conventional ventilation

The effects of changing tidal volume (VT) and frequency (f) on the distribution of ventilation during high-frequency ventilation (HFV) were assessed from the washout of nitrogen-13 by positron emission tomography. Six dogs, anesthetized and paralyzed, were studied in the supine position during conventional ventilation (CV) and during HFV at f of 3, 6, and 9 Hz. In CV and HFV at 6 Hz, VT was selected to achieve eucapnic arterial partial pressure of CO2 (37 +/- 3 Torr). At 3 and 9 Hz, VT was proportionally changed so that the product of VT and f remained constant and equal to that at 6 Hz. Mean residence time (MRT) of nitrogen-13 during washout was calculated for apical, midheart, and basal transverse sections of the lung and further analyzed for gravity-dependent, cephalocaudal and radial gradients. An index of local alveolar ventilation per unit of lung volume, or specific ventilation (spV), was calculated as the reciprocal of MRT. During CV vertical gradients of regional spV were seen in all sections with ventral (nondependent) regions less ventilated than dorsal (dependent) regions. Regional nonuniformity in gas transport was greatest for HFV at 3 and 6 Hz and lowest at 9 Hz and during CV. During HFV, a central region at the base of the lungs was preferentially ventilated, resulting in a regional time-averaged tracer concentration equivalent to that of the main bronchi. Because the main bronchi were certainly receiving fresh gas, the presence of this preferentially ventilated area, whose ventilation increased with VT, strongly supports the hypothesis that direct convection of fresh gas is an important mechanism of gas transport during eucapnic HFV. Aside from the local effect of increasing overall lung ventilation, this central area probably served as an intermediate shuttle station for the transport of gas between mouth and deeper alveoli when VT was less than the anatomic dead space.     

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     

Effects of mean airway pressure on gas transport during high-frequency ventilation in dogs

In 10 anesthetized, paralyzed, supine dogs, arterial blood gases and CO2 production (VCO2) were measured after 10-min runs of high-frequency ventilation (HFV) at three levels of mean airway pressure (Paw) (0, 5, and 10 cmH2O). HFV was delivered at frequencies (f) of 3, 6, and 9 Hz with a ventilator that generated known tidal volumes (VT) independent of respiratory system impedance. At each f, VT was adjusted at Paw of 0 cmH2O to obtain a eucapnia. As Paw was increased to 5 and 10 cmH2O, arterial PCO2 (PaCO2) increased and arterial PO2 (PaO2) decreased monotonically and significantly. The effect of Paw on PaCO2 and PaO2 was the same at 3, 6, and 9 Hz. Alveolar ventilation (VA), calculated from VCO2 and PaCO2, significantly decreased by 22.7 +/- 2.6 and 40.1 +/- 2.6% after Paw was increased to 5 and 10 cmH2O, respectively. By taking into account the changes in anatomic dead space (VD) with lung volume, VA at different levels of Paw fits the gas transport relationship for HFV derived previously: VA = 0.13 (VT/VD)1.2 VTf (J. Appl. Physiol. 60: 1025-1030, 1986). We conclude that increasing Paw and lung volume significantly decreases gas transport during HFV and that this effect is due to the concomitant increase of the volume of conducting airways.     

Inspiratory-to-expiratory time ratio and alveolar ventilation during high-frequency ventilation in dogs

It has been suggested that the increase in inspiratory flow rate caused by a decrease in the inspiratory-to-expiratory time ratio (I:E) at a constant tidal volume (VT) could increase the efficiency of ventilation in high-frequency ventilation (HFV). To test this hypothesis, we studied the effect of changing I:E from 1:1 to 1:4 on steady-state alveolar ventilation (VA) at a given VT and frequency (f) and at a constant mean lung volume (VL). In nine anesthetized, paralyzed, supine dogs, HFV was performed at 3, 6, and 9 Hz with a ventilator that delivered constant inspiratory and expiratory flow rates. Mean airway pressure was adjusted so that VL was maintained at a level equivalent to that of resting FRC. At each f and one of the I:E chosen at random, VT was adjusted to obtain a eucapnic steady state [arterial pressure of CO2 (PaCO2) = 37 +/- 3 Torr]. After 10 min of each HFV, PaCO2, arterial pressure of O2 (PaO2), and CO2 production (VCO2) were measured, and I:E was changed before repeating the run with the same f and VT. VA was calculated from the ratio of VCO2 and PaCO2. We found that the change of I:E from 1:1 to 1:4 had no significant effects on PaCO2, PaO2, and VA at any of the frequencies studied. We conclude, therefore, that the mechanism or mechanisms responsible for gas transport during HFV must be insensitive to the changes in inspiratory and expiratory flow rates over the VT-f range covered in our experiments.     

Pulmonary gas mixing during spontaneous breathing and at high-frequency ventilation

This work is intended to estimate the contribution of either laminar or turbulent dispersion during spontaneous breathing on one hand, and at high-frequency pulmonary ventilation on the other. For that purpose, we performed a computer simulation of a mathematical model of gas transport in the human airways governed by a combination of axial convection and longitudinal dispersion. Calculations were carried out by incorporating two dispersion coefficients, proposed by Taylor and Scherer respectively, into the mathematical model. Moreover, computations were performed with five constant flow rates and two inert heavy (SF₆) and light (He) gases to enhance the effect of mixing. It is concluded that Taylor laminar dispersion cannot play a significant role in the human airways; however, it seems that convective gas mixing with disturbed dispersion - corresponding to a regime of quasi-steady state-can account for most gas transport during spontaneous respiration and high-frequency ventilation.     

A new conventional and high-frequency ventilator for small animals

A pressure limited, time controlled ventilator has been designed especially for studies on experimental animals with severe respiratory distress syndrome (SRDS). Inspiration: Expiration (I:E) ratio (1:99-99:1) and frequency can be changed independently. Frequency ranged from 1 to 199/min in conventional ventilation (CV), while in high-frequency jet ventilation (HFJV) from 1 to 30 Hz. The gas delivery system consists of 3 magnetic valves (inspiration, expiration and HFJV, respectively) to ensure superposition of CV with HFJ or to use them separately. A monitoring unit switches off inspiration gas sources during HFJV if intratracheal pressure exceeds the alarm threshold. The device has been used in the following animal models: premature newborn rabbits with surfactant deficient lungs, emphysematous rats and guinea pigs as well as dogs and rabbits with SRDS due to lung lavage. Ventilation was most effective with an I:E ratio of 4:1 during pressure controlled CV, whereas during HFJV optimum gas exchange could be maintained with an I:E ratio of 1:4 and a frequency of 15 Hz in beagle dogs and 10 Hz in rabbits, respectively.     

Gas mixing in the airways of dog lungs during high-frequency ventilation

Washout of insoluble inert test gases of different diffusivity (He and SF6 or He and Ar) from dog lungs was studied during high-frequency ventilation (HFV). Test gas equilibrium and subsequent washout were performed with HFV, succeeding measurements being performed at different stroke volumes (1.5-2.5 ml/kg body wt), oscillation frequencies (10-30 Hz), and with different lung volumes (32-74 ml X kg-1). Test gas concentrations were continuously measured by a mass spectrometer. The time course of washout could be described as the sum of two exponentials. There were no consistent differences in the time courses of washout between He and SF6 or between He and Ar. It is concluded that gas mixing in the airways during HFV is not significantly limited by diffusion, and this is suggested to apply during HFV to steady-state transport of respiratory gases (e.g., O2 and CO2) as well as to the transient state of inert gas washout.     

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.     

Gas transport during high-frequency ventilation

During high-frequency small-volume ventilation (HFV), the transport rate of gas from the mouth to a lung region is a function of two conductances (conductance is the transfer rate of a gas divided by its partial pressure difference): regional longitudinal gas conductance along the airways (Grlongi) and gas conductance between lung regions (Ginter). Grlongi per unit regional lung (gas) volume [Grlongi/(Vr beta g)] was determined during HFV in 11 anesthetized paralyzed dogs lying supine. The distribution of Grlongi/(Vr beta g) was nearly uniform during HFV when stroke volumes were less than approximately two-thirds of the Fowler dead-space volume. By contrast, the distribution of Grlongi/(Vr beta g) was nonuniform when the stroke volume exceeded approximately two-thirds of the Fowler dead-space volume and the oscillation frequency was 5 Hz. Gas conductance along the airways per unit lung gas volume [average Glongi/(V beta g)], for the entire lung, increased with stroke volume at all frequencies, but for a given product of oscillation frequency and stroke volume, the average Glongi/(V beta g) was greater when stroke volume was large and oscillation frequency was low. The average Glongi/(V beta g) increased with frequency up to a maximal value; the frequency at which the maximum occurred depended on the kinematic viscosity of the inspired gas mixture.     

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.     

Lung and chest wall mechanics in rabbits during high-frequency body-surface oscillation

In eight anesthetized and tracheotomized rabbits, we studied the transfer impedances of the respiratory system during normocapnic ventilation by high-frequency body-surface oscillation from 3 to 15 Hz. The total respiratory impedance was partitioned into pulmonary and chest wall impedances to characterize the oscillatory mechanical properties of each component. The pulmonary and chest wall resistances were not frequency dependent in the 3- to 15-Hz range. The mean pulmonary resistance was 13.8 +/- 3.2 (SD) cmH2O.l-1.s, although the mean chest wall resistance was 8.6 +/- 2.0 cmH2O.l-1.s. The pulmonary elastance and inertance were 0.247 +/- 0.095 cmH2O/ml and 0.103 +/- 0.033 cmH2O.l-1.s2, respectively. The chest wall elastance and inertance were 0.533 +/- 0.136 cmH2O/ml and 0.041 +/- 0.063 cmH2O.l-1.s2, respectively. With a linear mechanical behavior, the transpulmonary pressure oscillations required to ventilate these tracheotomized animals were at their minimal value at 3 Hz. As the ventilatory frequency was increased beyond 6-9 Hz, both the minute ventilation necessary to maintain normocapnia and the pulmonary impedance increased. These data suggest that ventilation by body-surface oscillation is better suited for relatively moderate frequencies in rabbits with normal lungs.     

High-frequency ventilation of ducks and geese

We studied gas exchange in anesthetized ducks and geese artificially ventilated at normal tidal volumes (VT) and respiratory frequencies (fR) with a Harvard respirator (control ventilation, CV) or at low VT-high fR using an oscillating pump across a bias flow with mean airway opening pressure regulated at 0 cmH2O (high-frequency ventilation, HFV). VT was normalized to anatomic plus instrument dead space (VT/VD) for analysis. Arterial PCO2 was maintained at or below CV levels by HFV with VT/VD less than 0.5 and fR = 9 and 12 s-1 but not at fR = 6 s-1. For 0.4 less than or equal to VT/VD less than or equal to 0.85 and 3 s-1. less than or equal to fR less than or equal to 12 s-1, increased VT/VD was twice as effective as increased fR at decreasing arterial PCO2, consistent with oscillatory dispersion in a branching network being an important gas transport mechanism in birds on HFV. Ventilation of proximal exchange units with fresh gas due to laminar flow is not the necessary mechanism supporting gas exchange in HFV, since exchange could be maintained with VT/VD less than 0.5. Interclavicular and posterior thoracic air sac ventilation measured by helium washout did not change as much as expired minute ventilation during HFV. PCO2 was equal in both air sacs during HFV. These results could be explained by alterations in aerodynamic valving and flow patterns with HFV. Ventilation-perfusion distributions measured by the multiple inert gas elimination technique show increased inhomogeneity with HFV. Elimination of soluble gases was also enhanced in HFV as reported for mammals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of gas properties and waveform asymmetry on gas transport in a branching tube network

Local gas transport coefficients, quantifying longitudinal dispersion through a symmetrical constant-diameter tube network, have been measured during oscillation with both symmetrical and nonsymmetrical waveforms. Experiments were carried out over a range of conditions that would prevail in the central to lower airways during high-frequency ventilation at moderate frequency (5 Hz) and tidal volume (15-80 ml). Gas transport coefficients resulting from oscillation of three different resident-trace gas pairs were measured using a new analytic technique. This technique allowed rapid determination of the transport coefficient distribution along the entire network. Results demonstrate a small but significant influence attributable to changes in gas properties that is similar to that found in a straight tube and indicate that augmented dispersion is an important mechanism of axial transport. Gas transport coefficients were found to be unaffected by changes in flow waveform symmetry, suggesting that previously reported improvements in gas exchange associated with decreasing inspiratory to expiratory time ratios are not due to a change in local conditions such as asymmetry in the velocity profile.     

Simulation of gas transport due to cardiogenic oscillations

We simulated gas transport due to cardiogenic oscillations (CO) using a model developed to quantify the gas mixing due to high-frequency ventilation (16). The basic components of the model are 1) gas mixing by augmented transport, 2) symmetrical lung morphometry, and 3) a Lagrangian (moving) reference frame. The theoretical predictions of the model are in general agreement with published experimental studies that have examined the effect of CO on the nitrogen concentration obtained by intrapulmonary gas sampling and the effect of CO on regional and total anatomical dead space. Further, the model predicts that augmentation of gas transport due to CO is less, nearer to the alveolar regions of the lung, and that the effect of CO during normal tidal breathing is negligible, but that CO may contribute up to approximately 10% of the alveolar ventilation in patients with severe hypoventilation. The agreement between experimental and theoretical results suggests that it may not be necessary to invoke gas transport mechanisms specific to an asymmetrical bronchial tree to explain the major proportion of gas transport due to CO.     

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.     

Effect of mechanical load on tidal volume during high-frequency jet ventilation

High-frequency jet ventilation (HFJV) was studied in twelve deeply anesthetized, paralyzed dogs. Entrained volume and total expired volume were directly measured by integration of flow. Jet volume was computed from these measurements. Seven dogs were ventilated with a driving pressure of 10 psi at rates of 2 and 5 Hz for each of three mechanical loads: control, thoracoabdominal wrap, and histamine infusion. Both load conditions reduced total expired volume and entrained volume but had no effect on jet volume. Wrap reduced entrainment more at 2 Hz while the effect of histamine infusion was frequency independent. Control arterial blood gases demonstrated that PO2 was higher and PCO2 was lower during 2 Hz ventilation than during 5 Hz ventilation despite equivalent minute volumes. Five additional dogs were studied using control and wrap loads and an additional ventilator setting of 15 psi at 5 Hz. This group demonstrated that wrap reduces entrainment more at lower frequencies for ventilatory settings providing equivalent gas exchange. We conclude that increasing mechanical load reduces entrainment during HFJV and that this reduction is frequency dependent for restrictive loads.