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.     

Model of gas transport during high-frequency ventilation

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

Relationship for gas transport during high-frequency ventilation in dogs

Alveolar ventilation during high-frequency ventilation (HFV) was estimated from the washout of the positron-emitting isotope (nitrogen-13-labeled N2) from the lungs of anesthetized paralyzed supine dogs by use of a positron camera. HFV was delivered at a mean lung volume (VL) equal to the resting functional residual capacity with a ventilator that generated tidal volumes (VT) between 30 and 120 ml, independent of the animal's lung impedance, at frequencies (f) from 2 to 25 Hz, with constant inspiratory and expiratory flows and an inspiration-to-expiration time ratio of unity. Specific ventilation (SPV), which is equivalent to ventilation per unit of compartment volume, was found to follow closely the relation: SPV = 1.9(VT/VL)2.1 X f. From this relation and from arterial PCO2 measurements we found an expression for the normocapnic settings of VT and f, given VL and body weight (W). We found that the VL was an important normalizing parameter in the sense that VT/VL yielded a better correlation (r = 0.91) with SPV/f than VT/W (r = 0.62) or VT alone (r = 0.8).     

Gas exchange in healthy rabbits during high-frequency oscillatory ventilation

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.     

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.     

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.     

Radial and longitudinal compartmental analysis of gas transport during high-frequency ventilation

A model of gas exchange by low-tidal-volume (VT), high-frequency ventilation (HFV) is presented, based on the physical principles of dispersion. These are the nonuniformity of the velocity profile and the nonreversible mixing of fluid components in a diffusive manner. A numerical method was used to incorporate these principles into a quantitative model. The airways of a symmetrically bifurcating bronchial-tree model were partitioned in the radial direction into two concentric layers representing the kinematic dispersion by nonuniformity of the velocity profile. Mixing between the layers was invoked in proportion to the diffusivity and local dimensions. The effects of frequency (f), VT, shape of the velocity profile, and bronchial-model configuration were tested in the model, with favorable comparison to available experimental data. The model predicts that for a frequency-dependent velocity profile, the rate of tracer exchange is proportional to the square root of f and to the square of VT-V0, where V0 is a constant small volume under which gas exchange was nil. Intracycle asymmetric mixing is predicted to have a stronger effect on gas exchange than asymmetric velocity profile. Gas exchange when turbulent-flow regime is assumed is predicted to be less for the higher VT values than with laminar flow and with mixing by molecular diffusivity. This model was found to be didactic, flexible, and capable of modeling combinations of factors affecting either one of the two fundamental processes of dispersion.     

Effects of respiratory variables on regional gas transport during high-frequency ventilation

The regional effects of tidal volume (VT), respiratory frequency, and expiratory-to-inspiratory time ratio (TE/TI) during high-frequency ventilation (HFV) were studied in anesthetized and paralyzed dogs. Regional ventilation per unit of lung volume (spVr) was assessed with a positron camera during the washout of the tracer isotope 13NN from the lungs of 12 supine dogs. From the washout data, functional images of the mean residence time (MRT) of 13NN were produced and spVr was estimated as the inverse of the regional MRT. We found that at a constant VT X f product (where f represents frequency), increasing VT resulted in higher overall lung spV through the local enhancement of the basal spVr and with little effect in the apical spVr. In contrast, increasing VT X f at constant VT increased overall ventilation without significantly affecting the distribution of spVr values. TE/TI had no substantial effect in regional spVr distribution. These findings suggest that the dependency of gas transport during HFV of the form VT2 X f is the result of a progressive regional transition in gas transport mechanism. It appears, therefore, that as VT increases, the gas transport mechanism changes from a relative inefficient dispersive mechanism, dependent on VT X f, to the more efficient mechanism of direct fresh gas convection to alveoli with high regional tidal volume-to-dead-space ratio. A mathematical model of gas transport in a nonhomogeneous lung that exhibits such behavior is presented.     

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.     

Intra-airway gas mixing during high-frequency ventilation

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.