Inspiratory flow rate and dead space in dogs.

It is generally accepted that a stationary concentration front is established in the tracheobronchial tree during the inspiratory phase of single- and multiple-breath washouts. The anatomic position of this front, which is determined by the balance between diffusive flux toward the airway opening and convective flux toward the periphery, is frequently used to predict the effects of molecular diffusivity and inspiratory flow rate on dead space. Although there is substantial experimental evidence supporting the predictive effect of molecular diffusivity, there is little evidence regarding the effect of convective flow. This study confirmed the predictions for the effects of molecular diffusivity but contradicted those for the effects of inspiratory flow. We measured dead space by multiple- and single-breath inert gas washout techniques and also measured physiological dead space in dogs for inspiratory flow rates of 10-71 ml.kg-1.s-1. None of the three measures of dead space increased over the entire range of flow rate, as predicted by contemporary gas transport models. A possible explanation for these findings is that axial dispersion coefficients in the anatomic region where stationary fronts are believed to develop (respiratory bronchioles and alveolar ducts) significantly increase with convective flow rate rather than remain equal to molecular diffusivity.

Diffusivity dependence of multiple-breath washouts of lung periphery.

Subpleural concentrations of He and SF6 were measured during multiple-breath washouts from isolated dog lungs. Tidal volume, inspiratory flow, and frequency were in the normal range of canine ventilation. For each gas, there was a local minimum in concentration during inspiration (Cinsp) and a local maximum in concentration during exhalation (Cexp). SF6 exhibited a deeper inspiratory trough than He for each breath of every washout. For large tidal volumes (10-20 ml/kg), Cexp approximated a single exponential decay and He was cleared more rapidly than SF6. For small tidal volumes (2.5 ml/kg), Cexp was multiexponential and SF6 was cleared more rapidly than He. Cinsp/Cexp (a measure of the depth of the inspiratory trough) and the kinetics of Cexp decay were determined for washouts using a tidal volume of 10 and 20 ml/kg and different inspiratory flows. Under all conditions, an increase of inspiratory flow resulted in a deeper inspiratory trough for both He and SF6. For washouts using 10 ml/kg and 60 breaths/min, an increase of inspiratory flow increased the clearance of both gases. In washouts using lower ventilatory frequencies, gas clearance was independent of inspiratory flow. These findings are contrary to predictions of contemporary models of convection and diffusion in the lung. This study suggests that convective axial mixing and radial diffusion in the airways are important determinants of pulmonary gas transport.

Multiple gas washout during jet ventilation.

Simultaneous washouts of He, N2, and SF6 were monitored during jet ventilation with tidal volumes of 50-200 ml and rates of 1-2 Hz. Gas concentrations were measured from the trachea and from a lower lobe bronchus in six baboons by mass spectrometry. Washouts using large tidal volumes approximated single exponential decays with the relative exponential rates of decay being He fastest, SF4 slowest, and N2 intermediate. Washouts using smaller tidal volumes demonstrated a two-phase exponential decay pattern. During the fast phase, the relative exponential rates of decay were He slowest, SF6 fastest, and N2 intermediate, the reverse order seen during large-volume washouts. During the slow phase, the relative exponential rates of decay were He fastest, SF4 slowest, and N2 intermediate, the same order seen during large-volume washouts. The magnitude of the first phase observed from the lower lobe bronchus was less than that observed from the trachea. These data are consistent with a serial two-compartment transport model incorporating a limitation of molecular diffusion between the peripheral and proximal compartments. The more rapid clearance of less diffusible gases from the central airways during the first phase of washout was due to slower transport from the alveoli to the central airways rather than faster transport from the central airways to the airway opening.

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.

Fluid balance and the adult respiratory distress syndrome.

This study examined the effect of fluid balance on survival in ARDS. Of the 213 patients entered into a prospective data collection study, we evaluated 113 patients who met strict criteria for ARDS. Multiple variables were analyzed for as long as 14 days after intubation including cardiac output, pulmonary capillary wedge pressure, mean blood pressure, intake minus output (I-O), cumulative intake minus output (cum I-O), and change in weight (delta wt). We found significant differences in cum I-O and delta wt between survivors and nonsurvivors on almost every day. Survivors lost weight and had a significantly lower cum I-O compared with nonsurvivors. Logistic regression was used to determine if delta wt and cum I-O could predict survival. Patients who lost 3 kg or more weight had a much higher survival than did those who gained 3 kg or more weight (67 and 0%, respectively, on Day 14). Similar results were obtained using comparably low and high values for cum I-O. The logistic regression equations demonstrated that weight loss and low cumulative I-O correlated with improved survival. Although cause and effect relationships are difficult to determine from these types of analyses, they can be used to formulate prospective studies and predict survival in patients.

Nonuniformity of canine lung washout by high-frequency ventilation.

Ethane washout during low tidal volume (25-100 ml) high-frequency (3-40 Hz) ventilation (HFV) was studied in seven excised dog lungs. The lungs were initially equilibrated with 1% ethane, and then the concentration of ethane was monitored by mass spectrometry from multiple anatomic sites along the tracheobronchial tree during washout. We observed that the lung changed from a uniform distribution of ethane concentrations to a nonuniform distribution by a three-phase process. The first phase was nearly complete within the first 15 s and probably corresponds to concentration gradients being established in the central airways. During the second phase of washout, which lasted for several minutes, the concentrations in the various alveolar regions diverged. In the final phase, the regional concentrations remained at fixed ratios, and washout from all sites in the lung was at a constant fractional rate. These data are consistent with a model in which the duration of the second phase and the magnitude of the regional concentration differences established in this phase are dependent on both the magnitude of differences between regional transport paths and the nature of regional coupling by a common transport path to the airway opening.

Pathophysiology of soman intoxication in primates.

Adult baboons were monitored during intravenous infusion of Soman (1,2,2-trimethylpropyl ester, phosphonofluoridate). Three groups of animals were studied. Two groups were anesthetized with sodium pentobarbital (initial dose, 20 mg/kg), instrumented for measurement of systemic blood pressure (BP), pulmonary artery pressure, cardiac output (CO), ECG, ventilatory flow, translaryngeal pressure (PTL), transdiaphragmatic pressure (Pdi), transpulmonary pressure (PTP), diaphragm EMG, and efferent phrenic nerve traffic (Eph). One group received no Soman and served as controls. In the other group, Soman was infused over 10 min at doses of 13.1, 8.21, 4.92, or 3.3 micrograms/kg. The onset of intoxication occurred within 7-8 min (before the end of the 10-min infusion), manifested by muscular fasciculations, stridorous breathing, copious secretions, and atrioventricular arrhythmias. Mean BP decreased to 30 mm Hg by the combination of decreased CO and decreased vascular resistance. There was a dose-related response in the onset and duration of these effects. Apnea occurred in most animals and coincided with cessation of the Eph signal. Stimulation of the diaphragm via the phrenic nerve following apnea yielded Pdi values unchanged from baseline, indicating an intact neuromuscular apparatus. All animals required ventilatory support. Some surviving animals exhibited severe behavior changes. The third group of animals was studied without anesthesia. Instrumentation was performed 3 days before using a tether system for the measurement of BP, CO, and ECG, and an arterial line for blood withdrawal. Soman was infused over 10 min at a dose of 13.1 micrograms/kg. The onset of intoxication occurred within 2-3 min, manifested by hyperactivity, severe muscle fasciculations which simulated grand-mal convulsions, stridorous respiratory sounds, copious secretions, and cardiac arrhythmias. Apnea and severe lactic acid acidosis developed in all animals and all required ventilatory assistance. None recovered spontaneous ventilation at the end of 4 hr.

Oscillatory flow and quasi-steady behavior in a model of human central airways.

We studied biased oscillatory flow in a model of human central airways to examine under what conditions oscillatory flow deviated from steady flow. Although the steady flow resistance of the model was 25% less than the oscillatory flow resistance of the model at 15Hz, the overall inertance of the model did not change over the range of frequencies from 5 to 15 Hz, suggesting that frequency-dependent inertial distortion of velocity profiles did not alter central airway pressure-flow relationships over this frequency range. In a given terminal branch of the model, instantaneous oscillatory flow at 2 and 5 Hz could be predicted well from the steady flow distribution, but with increasing frequency the oscillatory flow from the branch deviated more from the steady flow predictions. A significant component of this deviation was due to a phase shift between predicted and measured oscillatory flow. We conclude that the major frequency-dependent behavior flow in the human central airways is a phasic redistribution of flow above 7 Hz, resulting from the asymmetric distribution of inertances in this structure.

Steady flow in a model of human central airways.

We studied the pressure-flow relationships and flow distribution under steady conditions in a model of human central airways, over a range of tracheal Reynolds' numbers (350-30,000) by using air or helium. We found that the Moody diagram [log coefficient of friction CF = delta P/[1/2 rho (V2/A2)] vs. log Reynolds' number (Re)] had a slope of -1 for Re less than 500, a slope 0 for Re greater than 10,000, and slopes between -1 and 0 for 500 less than or equal to Re less than or equal to 10,000. The distribution of flow among branches was dependent on tracheal Reynolds' number so that, as tracheal Reynolds' number increased, the upper lobes received proportionally less of the total flow than the lower lobes. Because the airways in the upper lobes generally had greater branching angles than those in the lower lobes, this result was consistent with the hypothesis that the effective resistances introduced by branching angles was flow dependent, increasing proportionally more the greater the angle.