Forced expiratory wheezes are a manifestation of airway flow limitation

To study the mechanism of generation of respiratory wheezes we examined the relationships between forced expiratory wheezes (FEW) and flow limitation in the lung. Tracheal lung sounds were measured in six healthy subjects during forced expiration through a flow-limiting valve in series with a high-impedance suction pump. Mouth pressure, esophageal pressure, transpulmonary pressure (Ptp), flow (V), and volume were also measured. For any flow rate, V was constant until the subject became flow limited. The onset of flow limitation was documented by a small change in V and a sudden change in Ptp, which was previously found by Olafsson and Hyatt to correspond to the beginning of the flow plateau of the isovolume pressure-flow curve (J. Clin. Invest. 48: 564-573, 1969). FEW started 107 +/- 45 ml (SD) after the onset of flow limitation. Additional 79 +/- 65 ml were exhaled between the onset of FEW to the final sharp drop in V. The frequency spectra of FEW were the same as those of respiratory wheezes found in obstructive airway diseases. Administration of inhaled bronchodilator (isoproterenol) did not eliminate the FEW, nor did it change their relationship to flow limitation. The sequence of events around the onset of FEW, and the tight correlation with the onset of flow limitation correspond well to recent experimental observations on the onset of flutter in collapsible, thick-walled latex tubes.     

Spectral content of forced expiratory wheezes during air, He, and SF6 breathing in normal humans.

The effect of gas density on the spectral content of forced expiratory wheezes was studied in the search for additional information on the mechanism of generation of respiratory wheezes. Five normal adults performed forced vital capacity maneuvers through four or five orifice resistors (0.4-1.92 cm ID) after breathing air, 80% He-20% O2, or 80% SF6-20% O2. Tracheal lung sounds, flow, volume, and airway opening (Pao) and esophageal (Pes) pressures were measured during duplicate runs for each orifice and gas. Wheezes were detected in running spectra of lung sounds by use of a frequency domain peak detection algorithm. The wheeze spectrograms were presented along side expiratory flow rate and transpulmonary pressure (Ptp = Pao - Pes) as function of volume. The frequencies and patterns of wheeze spectrograms were evaluated for gas density effects. We found that air, He, and SF6 had similar wheeze spectrograms. Both wheeze frequency and patterns (as function of volume) did not exhibit consistent changes with gas density. Speech tone, however, was substantially affected in the usual pattern. These observations support the hypothesis that airway wall vibratory motion, rather than gas phase oscillations, is the source of acoustic energy of wheezes.     

Respiratory dynamics during laughter.

Lung and chest wall mechanics were studied during fits of laughter in 11 normal subjects. Laughing was naturally induced by showing clips of the funniest scenes from a movie by Roberto Benigni. Chest wall volume was measured by using a three-dimensional optoelectronic plethysmography and was partitioned into upper thorax, lower thorax, and abdominal compartments. Esophageal (Pes) and gastric (Pga) pressures were measured in seven subjects. All fits of laughter were characterized by a sudden occurrence of repetitive expiratory efforts at an average frequency of 4.6 +/- 1.1 Hz, which led to a final drop in functional residual capacity (FRC) by 1.55 +/- 0.40 liter (P < 0.001). All compartments similarly contributed to the decrease of lung volumes. The average duration of the fits of laughter was 3.7 +/- 2.2 s. Most of the events were associated with sudden increase in Pes well beyond the critical pressure necessary to generate maximum expiratory flow at a given lung volume. Pga increased more than Pes at the end of the expiratory efforts by an average of 27 +/- 7 cmH2O. Transdiaphragmatic pressure (Pdi) at FRC and at 10% and 20% control forced vital capacity below FRC was significantly higher than Pdi at the same absolute lung volumes during a relaxed maneuver at rest (P < 0.001). We conclude that fits of laughter consistently lead to sudden and substantial decrease in lung volume in all respiratory compartments and remarkable dynamic compression of the airways. Further mechanical stress would have applied to all the organs located in the thoracic cavity if the diaphragm had not actively prevented part of the increase in abdominal pressure from being transmitted to the chest wall cavity.     

Effect of lung inflation on regional lung expansion in supine and prone rabbits

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Nonlinearity and harmonic distortion of dog lungs measured by low-frequency forced oscillations

The nonlinearity of lung tissues and airways was studied in six anesthetized and paralyzed open-chest dogs by means of 0.1-Hz sinusoidal volume forcing at mean transpulmonary pressures (Ptp) of 5 and 10 cmH2O. Lung resistance (RL) and elastance (EL) were determined in a 32-fold range (15-460 ml) of tidal volume (VT), both by means of spectrum analysis at the fundamental frequency and with conventional time-domain techniques. Alveolar capsules were used to separate the tissue and airway properties. A very small amplitude dependence was found: with increasing VT, the frequency-domain estimates of RL decreased by 5.3 and 14%, whereas EL decreased by 20 and 22% at Ptp = 5 and 10 cmH2O, respectively. The VT dependences of the time-domain estimates of RL were higher: 10.5 and 20% at Ptp = 5 and 10 cmH2O, respectively, whereas EL remained the same. The airway resistance increased moderately with flow amplitude and was smaller at the higher Ptp level. Analysis of the harmonic distortions of airway opening pressure and the alveolar pressures indicated that nonlinear harmonic production is moderate even at the highest VT and that VT dependence is homogeneous throughout the tissues. In three other dogs it was demonstrated that VT dependences of RL and EL were similar in situ and in isolated lungs at both Ptp levels.     

Effect of transpulmonary pressure on airway diameter and responsiveness of immature and mature rabbits.

We previously demonstrated that airway responsiveness is greater in immature than in mature rabbits; however, it is not known whether there are maturational differences in the effect of transpulmonary pressure (Ptp) on airway size and airway responsiveness. The relationship between Ptp and airway diameter was assessed in excised lungs insufflated with tantalum powder. Diameters of comparable intraparenchymal airway segments were measured from radiographs obtained at Ptp between 0 and 20 cmH(2)O. At Ptp > 8 cmH(2)O, the diameters were near maximal in both groups. With diameter normalized to its maximal value, changing Ptp between 8 and 0 cmH(2)O resulted in a greater decline of airway caliber in immature than mature airways. The increases in lung resistance (RL) in vivo at Ptp of 8, 5, and 2 cmH(2)O were measured during challenge with intravenous methacholine (MCh: 0.001-0.5 mg/kg). At Ptp of 8 cmH(2)O, both groups had very small responses to MCh and the maximal fold increases in RL did not differ (1.93 +/- 0.29 vs. 2.23 +/- 0.19). At Ptp of 5 and 2 cmH(2)O, the fold increases in RL were greater for immature than mature animals (13.19 +/- 1.81 vs. 3.89 +/- 0.37) and (17.74 +/- 2.15 vs. 4.6 +/- 0.52), respectively. We conclude that immature rabbits have greater airway distensibility and this difference may contribute to greater airway narrowing in immature compared with mature rabbits.     

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.     

Stress adaptation and low-frequency impedance of rat lungs

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of expiratory loading and hyperinflation on cardiac output during exercise.

Patients with obstructive lung disease are exposed to expiratory loads (ELs) and dynamic hyperinflation as a consequence of expiratory flow limitation. To understand how these alterations in lung mechanics might affect cardiac function, we examined the influence of a 10-cm H2O EL, alone and in combination with voluntary hyperinflation (ELH), on pulmonary pressures [esophageal (Pes) and gastric (Pg)] and cardiac output (CO) in seven healthy subjects. CO was determined by using an acetylene method at rest and at 40 and 70% of peak work. At rest and during exercise, EL resulted in an increase in Pes and Pg (7-18 cm H2O; P < 0.05) and a decrease in CO (from 5.3 +/- 1.8 to 4.5 +/- 1.4, 12.2 +/- 2.2 to 11.2 +/- 2.2, and 16.3 +/- 3.3 to 15.2 +/- 3.2 l/min for rest, 40% peak work, and 70% peak work, respectively; P < 0.05), which remained depressed after an additional 2 min of EL. With ELH, CO increased at rest and both exercise loads (relative to EL only) but remained below control values. The changes in CO were due to a reduction in stroke volume with a tendency for stroke volume to fall further with prolonged EL. There was a negative correlation between CO and the increase in expiratory Pes and Pg with EL (R = -0.58 and -0.60; P < 0.01), whereas the rise in CO with subsequent hyperinflation was related to a more negative Pes (R = 0.72; P < 0.01). In conclusion, EL leads to a reduction in CO, which appears to be primarily related to increases in expiratory abdominal and intrathoracic pressure, whereas ELH resulted in an improved CO, suggesting that lung inflation has little impact on cardiac function.     

Properties of steady maximal expiratory flow within excised canine central airways

Using our transistor model of the lung during forced expiration (J. Appl. Physiol. 62: 2013-2025, 1987), we recently predicted that 1) axially arranged choke points can exist simultaneously during forced expiration with sufficient effort, and 2) overall maximal expiratory flow may be relatively insensitive to nonuniform airways obstruction because of flow interdependence between parallel upstream branches. We tested these hypotheses in excised central airways obtained from five canine lungs. Steady expiratory flow was induced by supplying constant upstream pressure (Pupstream = 0-16 cmH2O) to the bronchi of both lungs while lowering pressure at the tracheal airway opening (16 to -140 cmH2O). Intra-airway pressure profiles obtained during steady maximal expiratory flow disclosed a single choke point in the midtrachea when Pupstream was high (2-16 cmH2O). However, when Pupstream was low (0 cmH2O), two choke sites were evident: the tracheal site persisted, but another upstream choke point (main carina or both main bronchi) was added. Flow interdependence was studied by comparing maximal expiratory flow through each lung before and after introduction of a unilateral external resistance upstream of the bronchi of one lung. When this unilateral resistance was added, ipsilateral flow always fell, but changes in flow through the contralateral lung depended on the site of the most upstream choke. When a single choke existed in the trachea, addition of the external resistance increased contralateral flow by 38 +/- 28% (SD, P less than 0.003). In contrast, when the most upstream choke existed at the main carina or in the bronchi, addition of the external resistance had no effect on contralateral maximal expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphological evidence for alveolar recruitment during inflation at high transpulmonary pressure

The effect of continuous inflation of lungs at 30 cmH2O transpulmonary pressure (Ptp) on air-space size was assessed by chord length-frequency distribution analysis. Lungs from gerbils were excised, allowed to collapse freely, and inflated to 30 cmH2O Ptp in a humidified chamber kept at 37 degrees C. When the lungs appeared fully inflated with no observable pleural surface atelectasis, the left lung was occluded while the right was maintained at 30 cmH2O for 10 min longer and then occluded. During this time, the right lung increased its volume from 70 to 100%. Then both lungs were quick frozen, freeze dried, and embedded in glycol methacrylate, and 1- to 2-microns-thick histological sections cut. Lungs from a control group of gerbils were similarly inflated to 30 cmH2O, both left and right were occluded, the left was quick frozen immediately, and the right was frozen 10 min later. Chord lengths of air spaces from cranial and caudal lobes of lungs were acquired using a Dapple Systems image analyzer, and a two-population frequency distribution was generated for analysis with an IBM PC. The results indicate that the volume increase during continuous inflation at 30 cmH2O Ptp was associated with a shift in the chord length distribution toward the smaller chord lengths. A two-population statistical analysis indicated that the inflation resulted in an increase in the relative proportion of smaller chord lengths, with no increase in the mean of this smaller population. We conclude that continuous inflation at 30 cmH2O Ptp results in alveolar recruitment.     

Respiratory muscle strength training with nonrespiratory maneuvers.

The diaphragm and abdominal muscles can be recruited during nonrespiratory maneuvers. With these maneuvers, transdiaphragmatic pressures are elevated to levels that could potentially provide a strength-training stimulus. To determine whether repeated forceful nonrespiratory maneuvers strengthen the diaphragm, four healthy subjects performed sit-ups and biceps curls 3-4 days/wk for 16 wk and four subjects served as controls. The maximal transdiaphragmatic pressure was measured at baseline and after 16 wk of training. Maximum static inspiratory and expiratory mouth pressures and diaphragm thickness derived from ultrasound were measured at baseline and 8 and 16 wk. After training, there were significant increases in diaphragm thickness [2.5 +/- 0.1 to 3.2 +/- 0.1 mm (mean +/- SD) (P < 0.001)], maximal transdiaphragmatic pressure [198 +/- 21 to 256 +/- 23 cmH2O (P < 0.02)], maximum static inspiratory pressure [134 +/- 22 to 171 +/- 16 cmH2O (P < 0.002)], maximum static expiratory pressure [195 +/- 20 to 267 +/- 40 cmH2O (P < 0.002)], and maximum gastric pressure [161 +/- 5 to 212 +/- 40 cmH2O (P < 0.03)]. These parameters were unchanged in the control group. We conclude that nonrespiratory maneuvers can strengthen the inspiratory and expiratory muscles in healthy individuals. Because diaphragm thickness increased with training, the increase in maximal pressures is unlikely due to a learning effect.     

Effects of pulse lung inflation on chest wall expiratory motor activity.

The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs (n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific.     

Size-related differences in parietal extrapleural and pleural liquid pressure distribution

The hydraulic pressure in the extrapleural parietal interstitium (Pepl) and in the pleural space over the costal side (Pliq) was measured in anesthetized spontaneously breathing supine adult mammals of increasing size (rats, dogs, and sheep) using saline-filled catheters and cannulas, respectively. From the Pliq and Pepl vs. lung height regressions it appears that in all species Pliq was significantly more subatmospheric than Pepl simultaneously measured at the same lung height. The vertical pleural liquid pressure gradient increased with size, amounting to -1, -0.69, and -0.44 cmH2O/cm in rats, dogs, and sheep, respectively. The vertical extrapleural liquid pressure gradient also increased with size, being -0.6, -0.52, and -0.33 cmH2O/cm in rats, dogs, and sheep, respectively. With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep. In all species Ptp increased, with lung height being greatest in the less dependent part of the pleural space.     

Alveolar liquid pressure in excised edematous dog lung with increased static recoil

Alveolar liquid pressure (Pliq) was measured by micropipettes in conjunction with a servo-nulling pressure measuring system in isolated air-inflated edematous dog lungs. Pliq was measured in lungs either washed with a detergent (0.01% Triton X-100) or subjected to refrigeration for 2-3 days followed by ventilation for 3 h. At 55% of total lung capacity (TLC, the volume at a transpulmonary pressure (Ptp) of 25 cmH2O before treatment), in both the Triton-washed and the ventilated lung, Ptp increased from 5 to 11 cmH2O, whereas Pliq, decreased from -3 to -11 cmH2O relative to alveolar air pressure. Similar increases in Ptp and decreases in Pliq were obtained at higher lung volumes. Alveolar surface tension (T) was estimated from the Laplace equation for a spherical air-liquid interface, assuming that the radius of curvature varies as (volume)n, for -1/3 less than n less than 1/3. For uniform expansion of alveoli (n = 1/3), estimated T was 6 and 18 dyn/cm at 55 and 85% TLC, respectively, before treatment and increased to 23 and 40 dyn/cm following either Triton washing or ventilation. If pericapillary interstitial fluid pressure (Pi) equaled Pliq in edematous lungs, increases in T might reduce Pi and increase extravascular fluid accumulation in lungs made stiff by either Triton washing or cooling and ventilation using large tidal volumes.     

Changes in upper airway resistance with lung inflation and positive airway pressure

The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra-thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP.     

Optimal electrode placement for noninvasive electrical stimulation of human abdominal muscles.

Abdominal muscles are the most important expiratory muscles for coughing. Spinal cord-injured patients have respiratory complications because of abdominal muscle weakness and paralysis and impaired ability to cough. We aimed to determine the optimal positioning of stimulating electrodes on the trunk for the noninvasive electrical activation of the abdominal muscles. In six healthy subjects, we compared twitch pressures produced by a single electrical pulse through surface electrodes placed either posterolaterally or anteriorly on the trunk with twitch pressures produced by magnetic stimulation of nerve roots at the T(10) level. A gastroesophageal catheter measured gastric pressure (Pga) and esophageal pressure (Pes). Twitches were recorded at increasing stimulus intensities at functional residual capacity (FRC) in the seated posture. The maximal intensity used was also delivered at total lung capacity (TLC). At FRC, twitch pressures were greatest with electrical stimulation posterolaterally and magnetic stimulation at T(10) and smallest at the anterior site (Pga, 30 +/- 3 and 33 +/- 6 cm H(2)O vs. 12 +/- 3 cm H(2)O; Pes 8 +/- 2 and 11 +/- 3 cm H(2)O vs. 5 +/- 1 cm H(2)O; means +/- SE). At TLC, twitch pressures were larger. The values for posterolateral electrical stimulation were comparable to those evoked by thoracic magnetic stimulation. The posterolateral stimulation site is the optimal site for generating gastric and esophageal twitch pressures with electrical stimulation.     

Flow limitation and wheezes in a constant flow and volume lung preparation

To facilitate the study of respiratory wheezes in an animal lung model, an isovolume, constant-flow excised dog lung preparation was developed. Dog lungs were inflated to 26 +/- 4 cmH2O and coated with layers of epoxy glue and polyester compound. A rigid shell 2 mm thick was obtained around the entire pleural surface and the extra-pulmonary airways. The adhesive forces between the pleura and the shell were strong enough to hold the lung distended after the inflation pressure was removed. Holes 2 mm diam were drilled through the shell over one of the lung lobes in an array, 4 cm across. The holes penetrated the pleural surface, so that constant flow could be maintained in the expiratory direction by activating a suction pump connected to the trachea. Downstream suction pressure and flow rate were measured with a mercury manometer and a rotameter, respectively. Sounds were recorded by a small (0.6 cm OD) microphone inserted into the trachea. When suction pressure was increased, flow initially increased to 31 +/- 3 l/min. Further increase of suction pressure caused only very slight additional increase in flow (i.e., flow limitation). During this plateau of flow, a pure tone was generated with acoustic properties similar to respiratory wheezes. Both the flow plateau and the wheezing sounds could be eliminated by freezing the lungs. It is concluded that wheezing sounds were associated with flow limitation in this preparation. It is suggested that the stable acoustic properties obtained by this preparation may become useful in the analysis of mechanisms of wheezing lung sounds generation.     

Size of pores of Kohn: influence of transpulmonary and vascular pressures

We investigated the influence of transpulmonary (Ptp) and vascular pressures on the size of the pores of Kohn in primary alveolar septa. Dogs lungs, perfused and ventilated in situ, were rapidly frozen with Freon 22 in zone II or III conditions following deflation to Ptp of 5, 15, or 25 cmH2O. Frozen samples were freeze-substituted for transmission electron microscopy. Five fields containing at least one pore each were selected randomly from each section of tissue, and the minimum diameter visible in the cut section was measured. For both zone II and III conditions, as Ptp increased, mean pore size increased. The mean pore size under zone III conditions was 1.2015, 1.788, and 2.249 micrometer for Ptp of 5, 15, and 25 cmH2O, respectively. For zone 2 conditions, the corresponding values were 1.1438, 1,8757, and 2.08 micrometer. For both zones II and III, increasing capillary hydrostatic pressure had no significant effect on pore size. The results support the notion that alveolar pores can increase collateral ventilation by dynamically stretching as Ptp increases. Capillary pressure does not influence pore size probably because of collagen fibers, which surround the pore lumen. Presumably, these fibers resist encroachment of capillaries on the pore lumen as vascular pressures increase.