Larynx vs. esophagus as reflexogenic sites for acid-induced bronchoconstriction in dogs.

Bronchoconstriction in asthmatic patients is frequently associated with gastroesophageal reflux. However, it is still unclear whether bronchoconstriction originates from the esophagus or from aspiration of the refluxate into the larynx and larger airway. We compared the effect of repeated esophageal and laryngeal instillations of HCl-pepsin (pH 1.0) on tracheal smooth muscle activity in eight anesthetized and artificially ventilated dogs. Saline was used as control. We used pressure in the cuff of an endotracheal tube (Pcuff) as a direct index of smooth muscle activity at the level of the larger airways controlled by vagal efferents. The Pcuff values of the first 60 s after instillations were averaged, and the difference from the baseline values was evaluated. Changes in Pcuff were significantly greater with laryngeal than with esophageal instillations (P = 0.0166). HCl-pepsin instillation into the larynx evoked greater responses than did saline (P = 0.00543), whereas no differences were detected with esophageal instillations. Repeated laryngeal exposure enhanced the responsiveness significantly (P < 0. 001). Our data indicate that the larynx is more important than the esophagus as a reflexogenic site for the elicitation of reflex bronchoconstriction in response to acidic solutions.     

Frequency and amplitude effects during high-frequency vibration ventilation in dogs

High-frequency external body vibration, combined with constant gas flow at the tracheal carina, was previously shown to be an effective method of ventilation in normal dogs. The effects of frequency (f) and amplitude of the vibration were investigated in the present study. Eleven anesthetized and paralyzed dogs were placed on a vibrating table (4-32 Hz). O2 was delivered near the tracheal carina at 0.51.kg-1.min-1, while mean airway pressure was kept at 2.4 +/- 0.9 cmH2O. Table vertical displacement (D) and acceleration (a), esophageal (Pes), and tracheal (Ptr) peak-to-peak pressures, and tidal volume (VT) were measured as estimates of the input amplitude applied to the animal. Steady-state arterial PCO2 (PaCO2) and arterial PO2 (PaO2) values were used to monitor overall gas exchange. Typically, eucapnia was achieved with f greater than 16 Hz, D = 1 mm, a = 1 G, Pes = Ptr = 4 +/- 2 cmH2O, and VT less than 2 ml. Inverse exponential relationships were found between PaCO2 and f, a, Pes, and Ptr (exponents: -0.69, -0.38, -0.48, and -0.54, respectively); PaCO2 decreased linearly with increased displacement or VT at a fixed frequency (17 +/- 1 Hz). PaO2 was independent of both f and D (393 +/- 78 Torr, mean +/- SD). These data demonstrate the very small VT, Ptr, and Pes associated with vibration ventilation. It is clear, however, that mechanisms other then those described for conventional ventilation and high-frequency ventilation must be evoked to explain our data. One such possible mechanism is forcing of flow oscillation between lung regions (i.e., forced pendelluft).     

Sound transmission between 50 and 600 Hz in excised pig lungs filled with air and helium.

This study measured transit time (TT) and attenuation of sound transmitted through six pairs of excised pig lungs. Single-frequency sounds (50-600 Hz) were applied to the tracheal lumen, and the transmitted signals were monitored on the tracheal and lung surface using microphones. The effect of varying intrapulmonary pressure (Pip) between 5 and 25 cmH(2)O on TT and sound attenuation was studied using both air and helium (He) to inflate the lungs. From 50 to approximately 200 Hz, TT decreased from 4.5 ms at 50 Hz to 1 ms at 200 Hz (at 25 cmH(2)O). Between approximately 200 and 600 Hz, TT was relatively constant (1.1 ms at upper and 1.5 ms at lower sites). Gas density had very little effect on TT (air-to-He ratio of approximately 1.2 at upper sites and approximately 1 at lower sites at 25 cmH(2)O). Pip had marked effects (depending on gas and site) on TT between 50 and 200 Hz but no effect at higher frequencies. Attenuation was frequency dependent between 50 and 600 Hz, varying between -10 and -35 dB with air and -2 and -28 dB with He. Pip also had strong influence on attenuation, with a maximum sensitivity of 1.14 (air) and 0.64 dB/cmH(2)O (He) at 200 Hz. At 25 cmH(2)O and 200 Hz, attenuation with air was about three times higher than with He. This suggests that sound transmission through lungs may not be dominated by parenchyma but by the airways. The linear relationship between increasing Pip and increasing attenuation, which was found to be between 50 and approximately 100 Hz, was inverted above approximately 100 Hz. We suggest that this change is due to the transition of the parenchymal model from open to closed cell. These results indicate that acoustic propagation characteristics are a function of the density of the transmission media and, hence, may be used to locate collapsed lung tissue noninvasively.     

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.     

Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.     

Respiratory input impedance in anesthetized paralyzed patients

Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube. Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz. From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz. Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz. Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz. We interpreted Zrs data in terms of a T network mechanical model. We represented the proximal branch by central airway resistance and inertance. The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility. The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues. When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al. (J. Appl. Physiol. 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated. The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity. Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties.     

Collateral flow resistance and time constants in dog and horse lungs

We studied collateral flow resistance in exsanguinated, excised lower lobes and accessory lobes of dog and horse lungs, respectively. A double lumen catheter obstructed a peripheral airway isolating a segment of the lobe. Oxygen flowed into the segment via a rotameter which measured flow (Vcoll) while the inner catheter recorded segment pressure (Ps). Gas delivered into the segment flowed out via collateral channels. Collateral flow resistance was calculated as (Ps - PL)/Vcoll, where PL = static transpulmonary pressure. Rcoll at PL = 20, 10, and 5 cm H2O averaged 0.24, 1.25, and 2.65 cmH2O.ml-1.s, respectively, in the dog, and 4.53, 6.00, and 12.62 cmH2O.ml-1.s in the horse. At a given PL, Rcoll measured during inflation. At constant PL, Rcoll increased with time at PL = 5 and 10 cmH2O, but was not time dependent at PL = 20 cmH2O. At constant PL, Rcoll increased at Vcoll increased. We conclude Rcoll is greater in horses than in dogs and is a function of PL, Ps - PL, and lung volume history in both species.     

Effect of increased surface tension and assisted ventilation on 99mTc-DTPA clearance

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of 99mTc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. 99mTc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of 99mTc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.     

Diaphragmatic blood flow in the dog

In anesthetized mongrel dogs we measured the blood flow in the left phrenic artery (Qdi), using an electromagnetic flow probe, before and during supramaximal phrenic nerve stimulation (pacing). This was done at constant respiratory rate (24/min) but at three different stimulation frequencies at a duty cycle of 0.4 (20, 50, and 100 Hz) and at three different duty cycles at a stimulation frequency of 50 Hz (duty cycle = 0.2, 0.4, and 0.8). Qdi was unchanged during diaphragm contraction until transdiaphragmatic pressure (Pdi) was greater than approximately 11 cmH2O, whereafter it began to decrease, reaching zero at Pdi approximately 20 cmH2O. Thus, when Pdi was greater than 21 cmH2O, all flow occurred during relaxation. Qdi averaged over the entire respiratory cycle (Qt) was less at duty cycle = 0.8 than under the other conditions. This was because of decreasing length of relaxation phase rather than a difference of relaxation phase flow (Qr), which was maximal during all conditions of phrenic stimulation. During pacing-induced fatigue, Qt actually rose slightly as Pdi fell. This was due to an increase in contraction phase flow while Qr remained constant. The relationship between Qt and tension-time index was not unique but varied according to the different combinations of duty cycle and stimulus frequency.     

Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0-30 V, constant 20 Hz) and frequency-response (0-25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.     

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)     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

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.     

Endotracheal tube cuff pressure in three hospitals, and the volume required to produce an appropriate cuff pressure

BACKGROUND: Cuff pressure in endotracheal (ET) tubes should be in the range of 20-30 cm H2O. We tested the hypothesis that the tube cuff is inadequately inflated when manometers are not used. METHODS: With IRB approval, we studied 93 patients under general anesthesia with an ET tube in place in one teaching and two private hospitals. Anesthetists were blinded to study purpose. Cuff pressure in tube sizes 7.0 to 8.5 mm was evaluated 60 min after induction of general anesthesia using a manometer connected to the cuff pilot balloon. Nitrous oxide was disallowed. After deflating the cuff, we reinflated it in 0.5-ml increments until pressure was 20 cmH2O. RESULTS: Neither patient morphometrics, institution, experience of anesthesia provider, nor tube size influenced measured cuff pressure (35.3 +/- 21.6 cmH2O). Only 27% of pressures were within 20-30 cmH2O; 27% exceeded 40 cmH2O. Although it varied considerably, the amount of air required to achieve a cuff pressure of 20 cmH2O was similar with each tube size. CONCLUSION: We recommend that ET cuff pressure be set and monitored with a manometer.     

Tracheal mucus rheology and epithelial potential difference in two day old puppies

The transepithelial potential difference (PD) value represents an integral of ion fluxes across the epithelium, and relates to the regulation of airway fluid. We studied six healthy two day old husky puppies for their tracheal mucus rheology and bioelectric properties, since this data in newborns are still unknown. PD (-mV, epithelium vs. subcutaneous space) was measured using the agar bridge technique in two locations - lower trachea and subglottic region. For the rheological analysis, the magnetic microrheometer was employed; data are presented as mechanical impedance log G* and loss tangent tan delta (1 rad/s). The mucus collection rate (mg/min) and the solid content (%) were determined by gravimetry. Mucociliary clearability, normalized to frog mucus, (MCFP) was determined directly by the frog palate method; a cough clearability index (CCI) was computed from simulated cough machine data obtained with mucus-like gels. The mucus collection rates and PD values were considerably lower than those observed in adult dogs; the mechanical impedance values were also reduced in comparison with adult data. The PD profile within the trachea (-13.9 +/- 1.2 mV lower trachea vs. -18.4 +/- 1.4 mV subglottical, i.e. more negative subglottically), however, is similar to that observed in adult dogs. Intratracheal profiles in mucus collection rate and mucus rheology were also comparable between puppies and adult dogs. The low collection rates in puppies, particularly in lower trachea, could indicate either reduced mucus volume or slower clearance. PD and collection rate correlated very strongly (r = 0.82, p = 0.0003). PD also correlated negatively with log G* (r = 0.73, p = 0.003) and positively with tan delta (r = 0.58, p = 0.03). MCFP and % solids correlated positively (r = 0.84, p = 0.0012), in contradistinction to the usual relationship, perhaps due to the presence of non-glycoprotein components that do not contribute to crosslink formation. The apparent maturation of airway bioelectric properties, mucus collection rate and mucus viscoelasticity are all consistent with the maturation of mucociliary clearance, which has previously been reported.     

Hindlimb muscular contraction reflexly decreases total pulmonary resistance in dogs

We have previously shown that contraction of the gracilis muscles of anesthetized dogs reflexly relaxes tracheal smooth muscle. We have also found that electrical stimulation of these afferents decreases total pulmonary resistance (TPR), a calculation that provides a functional index of airway caliber. Despite these findings, we have yet to show that muscular contraction reflexly decreases TPR. Therefore, in 11 alpha-chloralose-anesthetized dogs, we contracted the hindlimb muscles by electrically stimulating the L6-L7 ventral roots while measuring TPR breath by breath. We found that static contraction decreased TPR from 12.6 +/- 1.1 to 10.4 +/- 0.9 cmH2O X l-1 X s (P less than 0.05). This decrease was reflex in origin because it was prevented by section of the spinal roots innervating the working hindlimb. Repetitive twitch contractions (5 Hz) also reflexly decreased TPR, but the effect was smaller than that evoked by static contraction. The reflex decreases in TPR evoked by contraction were unaffected by propranolol but were abolished by atropine. We conclude that muscular contraction dilates the airways by a reflex mechanism whose efferent arm consists of a withdrawal of cholinergic input to airway smooth muscle.     

Clapping or percussion causes atelectasis in dogs and influences gas exchange

We examined the effects of 10 min of lower lateral chest wall percussion with a mechanical percussor or hand clapping in groups of anesthetized, paralyzed, and ventilated supine dogs. Mechanical percussion was applied at 10-16 Hz and caused an esophageal pressure swing (delta Pes) of 10-17 cmH2O. Hand clapping was applied at 4-7 Hz and caused a delta Pes of 6-17 cmH2O. At necropsy there were large reddened areas on the lateral surface of the underlying lung as well as smaller reddened areas on the hilar surfaces of both lungs and on the lateral surface of the opposite lung. These reddened regions were demonstrated to be atelectatic by postmortem lung inflation (which caused the reddened areas to disappear) and by microscopic examination. Despite the atelectasis, gas exchange improved toward the end of the percussion or clapping period. In four dogs that were ventilated for an additional 20 min after percussion, there was a tendency for gas exchange initially to worsen and then to gradually improve.     

Effect of inspiratory resistance and PEEP on 99mTc-DTPA clearance

Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). A submicronic aerosol containing 99mTc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval [k = 0.21 +/- 12%/min] when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP [0.76 +/- 0.28%/min, P less than 0.01]. When PEEP was increased to 15 cmH2O a marked increase in clearance occurred [k = 1.95 +/- 1.08%/min, P less than 0.001]. The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of 99mTc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP.     

Effect of intravenous papain on tracheal pressure-volume curves in rabbits

To investigate the effects of airway cartilage softening on tracheal mechanics, pressure-volume (PV) curves of excised tracheas were studied in 12 rabbits treated with 100 mg/kg iv papain, whereas 14 control animals received no pretreatment. The animals were killed 24 h after the injection and the excised specimens studied 24 h later. Treated tracheas exhibited decreased ability to withstand negative transmural pressures, reflected in increased collapse compliance: 6.2 +/- 2.1 vs. 2.0 +/- 0.5% peak volume (Vmax)/cmH2O means +/- SD, P less than 0.001, (Vmax = extrapolated maximal tracheal volume), increased kc (exponential constant that reflects the shape of collapse limb of the PV curve): 0.244 +/- 0.077 vs. 0.065 +/- 0.015 (P less than 0.001). The distension limb of the PV curve greater than 2.5 cmH2O transmural pressure (Ptm) was no different. Compliance between 0 and 2.5 cmH2O Ptm was increased in papain-treated rabbits: 4.97 +/- 1.73 vs. 2.30 +/- 0.31% Vmax/cmH2O (P less than 0.001). Tracheal volume, and therefore mean diameter, was decreased at 0 Ptm: 2.7 +/- 0.26 vs. 3.2 +/- 0.27 mm (P less than 0.001). We conclude that airway cartilage softening increases the compliance of the trachea at pressures less than 2.5 cmH2O Ptm.