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.     

高频双向喷射通气对麻醉犬的二氧化碳排除效能及其影响因素

观察了高频双向喷射通气(HFTJV)时反喷驱动压和通气频率对麻醉犬CO_2排除效能的影响以及潮气量(V_T)的变化特点。结果表明:在通气频率、正喷驱动压及吸/呼比均相同时,HFTJV时的Paco_2,V_T及FRC较高频喷射通气(HFJV)时均显著降低(P<0.05),Vco_2及pH均显著升高(P<0.01),而Pao_2和气道压则无明显改变。当HFTJV的反喷驱动压从2.06,4.31增加到6.57kPa/kg时,Paco_2,Vco_2,Pao_2,V_T及FRC等均无明显改变。无论在HFJV或HFTJV时,当通气频率从60,100增加到200次/min时,Paco_2均随之升高,并与V_T呈显著负相关。结果提示,HFTJV较HFJV具有更强的CO_2排除作用,HFTJV时的CO_2排除主要受潮气量的影响。     

Effect of tidal volume and anesthetic agent on airway responsiveness to histamine

Dose-response relationships for bronchoconstriction in response to aerosal histamine were assessed before and after vagotomy in 11 dogs anesthetized with barbiturates and in 9 dogs anesthetized with alpha-chloralose-urethan. The dose-response relationships following vagotomy were assessed during spontaneous ventilation and during muscular paralysis and mechanical ventilation with tidal volume (VT) similar to each animal's VT prior to vagotomy. After vagotomy the spontaneous VT of both groups increased but the VT of the alpha-chloralose-urethan group was significantly less than that of the barbiturate group. The histamine responsiveness of the animals anesthetized with barbiturates was significantly greater during mechanical ventilation when VT was reduced to prevagotomy levels compared with during spontaneous ventilation. In contrast, the histamine responsiveness of the alpha-chloralose-urethan group was not significantly changed by reducing VT to prevagotomy levels. In six other dogs anesthetized with pentobarbital sodium and studied after vagotomy, responsiveness to histamine aerosol during controlled ventilation with breaths of prevagotomy VT was greater than responsiveness during mechanical ventilation with large volume breaths given immediately afterward. Thus the magnitude of VT of dogs after vagotomy may influence airway responsiveness, and the influence of anesthetic agents on airway responsiveness after vagotomy may in part be due to their effects on VT. Furthermore, bronchodilation accompanying large volume ventilation persists after vagotomy, suggesting that it is not exclusively mediated by changes in parasympathetic activity.     

Respiratory resistance with histamine challenge by single-breath and forced oscillation methods

Relaxed expirations were obtained from five anesthetized dogs under control conditions and during various rates of intravenous infusion of histamine. All volume vs. time curves obtained from 20 ms to 2 s after the start of expiration were poorly described by a single exponential function but were fitted very well by a biexponential function. The resistance of the respiratory system as a function of frequency from 2 to 26 Hz was also determined by the forced oscillation method in the same dogs. Three two-compartment models of the respiratory system were identified from the exponentials fitted to the relaxed expiration data, and the one that had the most plausible parameter values under control conditions consisted of a homogeneous lung compartment connected to a viscoelastic compartment. Although a two-compartment model is arguably appropriate for describing relaxed expirations in normal dogs, physiological considerations suggest that there should be more than two interacting components with histamine infusion. We cannot identify all these components from our data, however. The equivalent complex impedance of the respiratory system was also calculated from the biexponential curves and showed significant variation in resistance over the frequency range from 0 to 2 Hz and negligible variation above 2 Hz. The calculated resistances at 2 Hz were consistently higher than those obtained by the forced oscillation method, which may be due to the nonlinear behavior of the respiratory system during relaxed expiration. We conclude that the single-breath and forced oscillation methods should be viewed as providing complimentary information about respiratory resistance.     

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspiratory resistive load detection in conscious dogs

The physiological mechanisms mediating the detection of mechanical loads are unknown. This is, in part, due to the lack of an animal model of load detection that could be used to investigate specific sensory systems. We used American Foxhounds with tracheal stomata to behaviorally condition the detection of inspiratory occlusion and graded resistive loads. The resistive loads were presented with a loading manifold connected to the inspiratory port of a non-rebreathing valve. The dogs signaled detection of the load by lifting their front paw off a lever. Inspiratory occlusion was used as the initial training stimulus, and the dogs could reliably respond within the first or second inspiratory effort to 100% of the occlusion presentations after 13 trials. Graded resistances that spanned the 50% detection threshold were then presented. The detection threshold resistances (delta R50) were 0.96 and 1.70 cmH2O.l-1.s. Ratios of delta R50 to background resistance were 0.15 and 0.30. The near-threshold resistive loads did not significantly change expired PCO2 or breathing patterns. These results demonstrate that dogs can be conditioned to reliably and specifically signal the detection of graded inspiratory mechanical loads. Inspiration through the tracheal stoma excludes afferents in the upper extrathoracic trachea, larynx, pharynx, nasal passages, and mouth from mediating load detection in these dogs. It is unknown which remaining afferents (vagal or respiratory muscle) are responsible for load detection.     

Hemodynamic effects of synchronous high-frequency jet ventilation during acute hypovolemia

We studied the effects of synchronous cardiac cycle-specific high-frequency jet ventilation (HFJV) in pentobarbital-anesthetized, splenectomized, closed-chest dogs to test the hypothesis that phasic inspiratory increases in intrathoracic pressure (ITP) selectively timed to specific periods of the cardiac cycle have different hemodynamic effects during both hypovolemia (acute hemorrhage, 20 ml/kg) and neurogenic vasomotor shock (hexamethonium, 10 mg/kg) than those observed during normovolemic control conditions. Ventricular stroke volumes (SV) were measured by electromagnetic flow probes. The influence of changes in venous return (VR) on the subsequent hemodynamic response to synchronous HFJV was analyzed using instantaneous VR curves (M. R. Pinsky, J. Appl. Physiol. 56:765-771, 1984). During hemorrhage the VR curve was shifted leftward with concomitant reductions in apneic SV (15.4 +/- 3.8 to 11.2 +/- 3.6 ml, mean +/- SD), (P less than 0.01) that were accentuated by HFJV (P less than 0.01), except when the phasic inspiratory increases in ITP during HFJV were timed to occur during late diastole (-4% apneic SV, NS). SV was greater with late diastolic pulses than with other timed synchronous ITP pulses during hypovolemia (P less than 0.01). During ganglionic blockade, arterial pressure decreased (139 +/- 14 to 76 +/- 18 Torr, P less than 0.001), but VR was preserved at control levels, and no significant cardiac cycle-specific HFJV effects occurred. We conclude that SV reductions associated with positive-pressure ventilation during acute hypovolemia are minimized by HFJV synchronized to late diastole but that this effect is preload dependent.     

Ventilation of an additional dead space

The authors studied the question of the completeness of ventilation of an additional dead space in the form of a tube 3 cm in diameter and with a volume of 600 ml. Seven young volunteers were examined while breathing with and without the tube, seated at rest and during a two-grade exercise load on a bicycle ergometer. The criterion of ventilation of the tube was enlargement of the dead space by 600 ml during breathing through the tube. The functional dead space was always calculated from the tidal volume and the CO2 concentration in mixed expired air and in an end-tidal sample, using the Bohr equation. In every case, the tube was found to be completely ventilated by breathing, both under resting conditions and during exercise. In breathing during the bicycle exercise, the ratio of the functional dead space to tidal volume fell from 0.3 to 0.19 and a similar decrease was recorded in breathing through the tube.     

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.     

Extracorporeal bicarbonate space after bicarbonate or a bicarbonate-carbonate mixture in acidotic dogs

The effects of sodium bicarbonate and a bicarbonate-carbonate mixture on expired CO2 and the volume of distribution of bicarbonate were studied in eight anesthetized, paralyzed, and ventilated dogs made acidotic with HCl (5 mmol/kg) infused over 90 min. Both sodium bicarbonate and Carbicarb resulted in systemic alkalinization and comparable increases in the serum bicarbonate at 50 min (7.07 +/- 0.91 vs. 7.99 +/- 0.77, respectively; P = NS). Sodium bicarbonate infusion resulted in an increase in CO2 excretion that accounted for a fractional CO2 excretion of 0.20 +/- 0.09, whereas infusion of a bicarbonate-carbonate mixture resulted in a fractional CO2 excretion of -0.06 +/- 0.09 (P less than 0.01). The uncorrected volume of distribution of bicarbonate after sodium bicarbonate infusion was higher than that seen with the bicarbonate-carbonate mixture (0.60 +/- 0.07 vs. 0.34 +/- 0.03 l/kg; P less than 0.01). However, when the volume of bicarbonate distribution was corrected for expired CO2, there was no difference between treatment with sodium bicarbonate and the bicarbonate-carbonate mixture (0.44 +/- 0.07 vs. 0.38 +/- 0.04 l/kg; P = NS). These data demonstrate that, in this animal model of acidosis, sodium bicarbonate treatment of systemic acidosis is accompanied by a generation of a considerable amount of CO2, whereas treatment with a bicarbonate-carbonate mixture is not. This suggests that in states of impaired ventilation, a bicarbonate-carbonate mixture may offer more efficient systemic alkalinization and may be associated with less CO2 generation than sodium bicarbonate.     

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.     

Hemodynamic effects of synchronous high-frequency jet ventilation in mitral regurgitation

We tested the hypothesis that increases in intrathoracic pressure (ITP), by decreasing the pressure gradient for anterograde left ventricular (LV) ejection, should augment cardiac output in acute mitral regurgitation (MR). In a pentobarbital-anesthetized closed-chest canine model, LV stroke volume (SLLV) was measured by integration from an aortic flow probe signal. MR was induced by a regurgitant ring. ITP was elevated over apnea by means of intermittent positive-pressure ventilation (IPPV), asynchronous (asynch) high-frequency jet ventilation (HFJV), and cardiac cycle-specific (synch) HFJV. IPPV resulted in the greatest increase in ITP. MR caused a fall in SVLV and a rise in LV filling pressure that were not altered by IPPV. Compared with IPPV or apnea, both asynch and synch HFJV increased SVLV and reduced LV filling pressures (P less than 0.05). Systolic synch HFJV induced a greater increase in SVLV (32%) than diastolic synch HFJV (26%) despite similar ventilatory settings. Our data suggest that when LV contractility is normal but MR impairs forward flow, cardiac cycle-specific increases in ITP will augment forward flow.     

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)     

Effect of hypoxia on immediate ventilatory load response in dogs.

The effective elastance of the respiratory system (which has been previously shown to provide an index of the ability of the respiratory musculature to compensate rapidly for transient mechanical ventilatory loads) was measured in six hypoxic dogs to determine whether hypoxia hindered immediate load-compensatory mechanisms. The effective elastance value was computed from measurements of control tidal volume and the pressure developed at the airway opening during the first inspiratory effort following airway occlusion at FRC. The mean effective elastance was 197 cmH2O/l while the animals were breathing room air and did not change significantly when the animals were rendered hypoxic by reducing the inspired oxygen concentration, in five dogs, or by controlled hemorrhage, in two dogs. It was concluded that inasmuch as effective elastance measurements remain constant during hypoxia, the stability of ventilation is not significantly impaired in this situation.     

Effects of positive end-expiratory pressure on the right ventricle

Transmural cardiac pressures, stroke volume, right ventricular volume, and lung water content were measured in normal dogs and in dogs with oleic acid-induced pulmonary edema (PE) maintained on positive-pressure ventilation. Measurements were performed prior to and following application of 20 cmH2O positive end-expiratory pressure (PEEP). Colloid fluid was given during PEEP for ventricular volume expansion before and after the oleic acid administration. PEEP significantly increased pleural pressure and pulmonary vascular resistance but decreased right ventricular volume, stroke volume, and mean arterial pressure in both normal and PE dogs. Although the fluid infusion during PEEP raised right ventricular diastolic volumes to the pre-PEEP level, the stroke volumes did not significantly increase in either normal dogs or the PE dogs. The fluid infusion, however, significantly increased the lung water content in the PE dogs. Following discontinuation of PEEP, mean arterial pressure, cardiac output, and stroke volume significantly increased, and heart rate did not change. The failure of the stroke volume to increase despite significant right ventricular volume augmentation during PEEP indicates that positive-pressure ventilation with 20 cmH2O PEEP decreases right ventricular function.     

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.     

Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans.

We studied the capacity of four "normal" and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within +/-3-5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.     

Input impedance and peripheral inhomogeneity of dog lungs.

Tracheal pressure, central airflow, and alveolar capsule pressures in cardiac lobes were measured in open-chest dogs during 0.1- to 20-Hz pseudorandom forced oscillations applied at the airway opening. In the interval 0.1-4.15 Hz, the input impedance data were fitted by four-parameter models including frequency-independent airway resistance and inertance and tissue parts featuring a marked negative frequency dependence of resistance and a slight elevation of elastance with frequency. The models gave good fits both in the control state and during histamine infusion. At the same time, the regional transfer impedances (alveolar pressure-to-central airflow ratios) showed intralobar and interlobar variabilities of similar degrees, which increased with frequency and were exaggerated during histamine infusion. Results of simulation studies based on a lung model consisting of a central airway and a number of peripheral units with airway and tissue parameters that were given independent wide distributions were in agreement with the experimental findings and showed that even an extremely inhomogeneous lung structure can produce virtually homogeneous mechanical behavior at the input.     

Control and evaluation of high-frequency jet ventilation: mechanical lung model

Ventilation systems that operate at high-frequency and deliver small volumes have the potential to provide adequate alveolar ventilation without excessive pulmonary pressures. One way of producing high-frequency ventilation is by use of jet bursts of an input gas through a cannula controlled by a solenoid valve. This high-frequency jet ventilation has yet to be quantitatively analysed for optimal clinical use. From an analysis of the jet-producing device, we obtained a quantitative relationship which allowed us to predict the gas volume of a jet burst (V_jet) from the driving pressure (P_d), and the jet duration (t_I). The device was applied to a mechanical lung model (a tube attached to an elastic bag corresponding to the lung airway and alveolar space). We examined how the control variables of the jet ventilation system changed the bag (alveolar) volume with respect to V_jet, the volume of entrained gas, and the volume of shunted gas. Using a nitrogen washout analysis, we evaluated the operating lung volume, effective dead-space volume (V_eds), and effective ventilation rate (V_eff). We found that V_eds is independent of the individual effects of jet cycle frequency, duty cycle, cannula diameter, and entrainment fraction. While V_eds was not affected significantly by the shape of the airway, it did depend on the distance of the jet cannula tip to the ventilated bag (or alveolar region) and on the tidal volume.     

Radiographic visualization of airway wall movement during oscillatory flow in dogs

It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670-677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7-9% of the mean with VT of 50 ml and 9-18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10-47% with VT of 50 ml, and during vagal stimulation diameters changed 7-20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)