Lung volumes after an increase in lung distension in pneumonectomized ferrets

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3-6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2-3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3-5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.     

Effects of swim training on lung volumes and inspiratory muscle conditioning

Lung volumes and inspiratory muscle (IM) function tests were measured in 16 competitive female swimmers (age 19 +/- 1 yr) before and after 12 wk of swim training. Eight underwent additional IM training; the remaining eight were controls. Vital capacity (VC) increased 0.25 +/- 0.25 liters (P less than 0.01), functional residual capacity (FRC) increased 0.39 +/- 0.29 liters (P less than 0.001), and total lung capacity (TLC) increased 0.35 +/- 0.47 (P less than 0.025) in swimmers, irrespective of IM training. Residual volume (RV) did not change. Maximum inspiratory mouth pressure (PImax) measured at FRC changed -43 +/- 18 cmH2O (P less than 0.005) in swimmers undergoing IM conditioning and -29 +/- 25 (P less than 0.05) in controls. The time that 65% of prestudy PImax could be endured increased in IM trainers (P less than 0.001) and controls (P less than 0.05). All results were compared with similar IM training in normal females (age 21.1 +/- 0.8 yr) in which significant increases in PImax and endurance were observed in IM trainers only with no changes in VC, FRC, or TLC (Clanton et al., Chest 87: 62-66, 1985). We conclude that 1) swim training in mature females increases VC, TLC, and FRC with no effect on RV, and 2) swim training increases IM strength and endurance measured near FRC.     

Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons

To test the hypothesis that hyaline membrane disease (HMD) has a multifactorial etiology in which barotrauma plays a major role, we compared the immediate institution of high-frequency oscillatory ventilation (HFOV; 15 Hz, n = 5) with positive-pressure ventilation with positive end-expiratory pressure (PPV; n = 7) in premature baboons (140-days gestation) with HMD. Measurements of ventilation settings and physiological parameters were obtained and arterial-to-alveolar O2 (PaO2-to-PAO2) ratio and oxygenation index [(PaO2/PAO2)-to-mean airway pressure ratio (IO2)] were calculated. At death (24 h), static pressure-volume (PV) curves were performed, and phospholipids (PL) and platelet-activating factor (PAF) were measured in lung lavage fluid. Morphological inflation patterns were analyzed using a panel of standards. By design, mean airway pressure was initially higher (19 vs. 13 cmH2O) in the HFOV animals. PaO2-to-PAO2 ratio and IO2 progressively deteriorated in the PPV animals and then stabilized at significantly lower levels than with HFOV. PV curves from HFOV animals had significant increases in lung volume at maximum distending pressure, deflation volume at 10 cmH2O, and hysteresis area compared with PPV, which showed no hysteresis. Seven of seven PPV and only one of five HFOV animals had morphological findings of HMD. PL amount and composition in both groups were consistent with immaturity, even though the quantity was significantly greater in the PPV group. PAF was present (greater than or equal to 0.10 pmol) in six of seven PPV and in the only HFOV animal with HMD. We conclude that HFOV protected PL-deficient premature baboons from changes in gas exchange, lung mechanics, and morphology typical of HMD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acute pleural effusion on respiratory system mechanics in dogs

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.     

Effect of mild-to-moderate airflow limitation on exercise capacity

To determine the effect of mild-to-moderate airflow limitation on exercise tolerance and end-expiratory lung volume (EELV), we studied 9 control subjects with normal pulmonary function [forced expired volume in 1 s (FEV1) 105% pred; % of forced vital capacity expired in 1 s (FEV1/FVC%) 81] and 12 patients with mild-to-moderate airflow limitation (FEV1 72% pred; FEV1/FVC % 58) during progressive cycle ergometry. Maximal exercise capacity was reduced in patients [69% of pred maximal O2 uptake (VO2max)] compared with controls (104% pred VO2max, P less than 0.01); however, maximal expired minute ventilation-to-maximum voluntary ventilation ratio and maximal heart rate were not significantly different between controls and patients. Overall, there was a close relationship between VO2max and FEV1 (r2 = 0.62). Resting EELV was similar between controls and patients [53% of total lung capacity (TLC)], but at maximal exercise the controls decreased EELV to 45% of TLC (P less than 0.01), whereas the patients increased EELV to 58% of TLC (P less than 0.05). Overall, EELV was significantly correlated to both VO2max (r = -0.71, P less than 0.001) and FEV1 (r = -0.68, P less than 0.001). This relationship suggests a ventilatory influence on exercise capacity; however, the increased EELV and associated pleural pressures could influence cardiovascular function during exercise. We suggest that the increase in EELV should be considered a response reflective of the effect of airflow limitation on the ventilatory response to exercise.     

Corticosteroid potentiation of surfactant dose response in preterm rabbits

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 days gestational age. Both corticosteroid-treated and control animals then received exogenous natural rabbit surfactant at birth at doses of 0-75 mg lipid/kg. After 10 min of ventilation at tidal volumes of 12-15 ml/kg, static pressure-volume measurements were made. At all surfactant doses there was a significantly higher maximal lung volume, higher dynamic compliance, and lower pressure requirement in the corticosteroid-treated than in the control rabbits (P less than 0.01). Control animals showed incremental improvements in dynamic compliances and maximal lung volumes up to a dose of 50 mg/kg, whereas corticosteroid treated animals improved to a maximum at the low dose of 15 mg/kg (P less than 0.01). However, surface tension as assessed by lung stability index improved with increasing surfactant dose but was not significantly different between corticosteroid-treated and control animals at a given dose. The results imply that maternal corticosteroid treatment potentiates surfactant replacement by a change in lung structure that is independent of surface tension effects.     

Lung volumes during low-intensity steady-state cycling

The use of inspiratory capacity (IC) to estimate end-expiratory lung volume (EELV) during exercise has been questioned because of the assumption of constant total lung capacity (TLC). To investigate lung volumes during low-intensity steady-state cycling, we measured EELV by the open-circuit N2 washout method (MR-1, currently Sensormedics 2100) in eight healthy men while at rest and during unloaded and 60-W cycling. TLC was calculated by adding EELV and IC. Measurement variation of TLC was 142 ml at rest, 121 ml during unloaded cycling, and 158 ml during 60-W cycling. TLC did not differ significantly among the three conditions studied. EELV decreased during unloaded (P less than 0.002) and 60-W cycling (P less than 0.001) compared with rest. End-inspiratory lung volume increased only during 60-W cycling (P = 0.03). The decrease in EELV accounted for 100% of the increase in tidal volume during unloaded cycling. Although minute ventilation was similar in the subjects during unloaded cycling, we noted that breathing patterns varied among the subjects. The increase in respiratory frequency was negatively correlated to the change in tidal volume (R2 = 0.54, P = 0.038) and to the change in end-inspiratory lung volume (R2 = 0.68, P = 0.012). We conclude that TLC does not differ significantly during low-intensity steady-state cycling and that use of IC to estimate changes in EELV is appropriate.     

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.     

Corticosteroids and surfactant increase lung volumes and decrease rupture pressures of preterm rabbit lungs

We measured the effects of corticosteroids and surfactant individually and in combination on lung pressure-volume relationships, rupture pressures, and rupture volumes. Pregnant does were injected with betamethasone (0.1 mg/kg per day im) or vehicle on days 24 and 25 of gestation, and fetal rabbits were delivered on days 26 and 27. Natural surfactant (50 mg/kg body wt) was instilled intratracheally into half of the lungs after tracheotomy. After nine cycles of inflation with air to 40 cmH2O and deflation, air pressure-volume curves were measured. Then the lungs were filled with air to rupture, and rupture volume and pressure were recorded. Both corticosteroids and surfactant caused an increase in maximal lung volumes (P less than 0.01) and a decrease of lung rupture pressures (P less than 0.01) compared with controls. The effects of corticosteroids plus surfactant on lung volumes were the sum of each effect individually, but rupture pressures were the same as those for corticosteroids or surfactant alone. Surfactant, in addition, caused an increase in lung stability at deflation, an effect that was not evident in the corticosteroid-treated groups. Measurements of saturated phosphatidylcholine in alveolar washes and lung tissue indicated comparable values in the corticosteroid and control groups. We conclude that changes in static properties and rupture pressures presumably reflect changes in lung structure caused by corticosteroids that are independent of a corticosteroid effect on surfactant pool sizes.     

Effect of age on changes in flow rates and airway conductance after a deep breath

The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways.     

Relations among alveolar surface tension, surface area, volume, and recoil pressure

For pulmonary structure-function analysis excised rabbit lungs were fixed by vascular perfusion at six points on the pressure-volume (P-V) curve, i.e. at 40, 80, and 100% of total lung capacity (TLC) on inflation, at 80 and 40% TLC on deflation, and at 80% TLC on reinflation. Before fixation alveolar surface tensions (gamma) were measured in individual alveoli over the entire P-V loop, using an improved microdroplet method. A maximal gamma of approximately 30 mN/m was measured at TLC, which decreased during lung deflation to about 1 mN/m at 40% TLC. Surface tensions were considerably higher on the inflation limb starting from zero pressure than on the deflation limb (gamma-V hysteresis). In contrast, the corresponding alveolar surface area-volume (SA-V) relationship did not form a complete hysteresis over the entire volume range. There was a considerable difference in SA between lungs inflated to 40% TLC (1.49 +/- 0.11 m2) and lungs deflated to 40% TLC (2.19 +/- 0.21 m2), but at 80% TLC the values of SA were essentially the same regardless of the volume history. The data indicate that the gamma-SA hysteresis is only in part accountable for the P-V hysteresis and that the determinative factors of alveolar geometry change with lung volume. At low lung volumes airspace dimensions appear to be governed by an interplay between surface and tissue forces. At higher lung volumes the tissue forces become predominant.     

Effects of acute hyperinflation on chest wall mechanics in dogs

We studied chest wall mechanics at functional residual capacity (FRC) and near total lung capacity (TLC) in 14 supine anesthetized and vagotomized dogs. During breathing near TLC compared with FRC, tidal volume decreased (674 +/- 542 vs. 68 +/- 83 ml; P less than 0.025). Both inspiratory changes in gastric pressure (4.5 +/- 2.5 vs. -0.2 +/- 2.0 cmH2O; P less than 0.005) and changes in abdominal cross-sectional area (25 +/- 17 vs. -1.0 +/- 4.2%; P less than 0.001) markedly decreased; they were both often negative during inspiration near TLC. Parasternal intercostal shortening decreased (-3.0 +/- 3.7 vs. -2.0 +/- 2.7%), whereas diaphragmatic shortening decreased slightly more in both costal and crural parts (costal -8.4 +/- 2.9 vs. -4.3 +/- 4.1%, crural -22.8 +/- 13.2 vs. -10.0 +/- 7.5%; P less than 0.05). As a result, the ratio of parasternal to diaphragm shortening increased near TLC (0.176 +/- 0.135 vs. 0.396 +/- 0.340; P less than 0.05). Electromyographic (EMG) activity in the parasternals slightly decreased near TLC, whereas the EMG activity in the costal and crural parts of the diaphragm slightly increased. We conclude that 1) the mechanical outcome of diaphragmatic contraction near TLC is markedly reduced, and 2) the mechanical outcome of parasternal intercostal contraction near TLC is clearly less affected.     

Lung volume and compliance in neonatal rats

Lung volumes and static lung compliance were measured in decapitated three day-old neonatal Long Evans' rat pups. Compliance was measured in situ (open chest method) using a water manometer and syringe system. Mean total lung capacity at 20 cm H2O pressure (TLC20) was 0.678 ml. Minimum lung volume after experimental inflation was 0.197 +/- 0.048 ml, and vital capacity was 0.56 ml (Vmax20). The mean lung compliance value for the approximate tidal loop (between 3 and 12 cm H2O) equalled 26.2 microliters air/cm H2O for the inflation limb and 23.1 microliters/cm H2O for the deflation limb.     

An apparatus for the measurement of lung volume and compliance in mice

Pressure-volume (P-V) curves and total lung capacity (TLC) were measured in excised lung of mice using a water manometer and a closed system in which the humidity and temperature were controlled. In pathogen-free mice there are no significant differences in elastic properties of these lungs in relation to their age. The measured TLC in those normal mice was approximately 2.9 ml. This relatively simple apparatus which allows one to make sensitive and accurate measurements of pulmonary function in mice and other small animals.     

Causes of error of respiratory pressure-volume curves in paralyzed subjects

Respiratory pressure-volume (PV) curves are commonly obtained in paralyzed patients by relating airway pressure to volume changes of a syringe (Vsyr). This is based on the implicit assumption that changes in thoracic volume (Vtho) and Vsyr are equal. We undertook to verify this assumption through simultaneous measurements of Vtho by respiratory inductive plethysmography and Vsyr in six comatose, paralyzed, intubated patients. At any constant Vsyr, Vtho fell and was smaller on deflation than on inflation during inflation-deflation (ID) cycle. The rate of fall was 110 +/- 64 (SD) ml/min. During ID cycles lasting 76 +/- 7 s, thoracic PV curves showed less hysteresis and a larger compliance on deflation than PVsyr curves (12 +/- 2 vs. 18 +/- 6% and 73 +/- 13 vs. 67 +/- 12 ml/cmH2O, P less than 0.05). With PVsyr curves, hysteresis increased and compliance on deflation decreased with increasing rate of fall of Vtho. We submit that the difference between changes in Vsyr and Vtho is best explained by gas exchange and should be taken into account when performing PV curves with a syringe in paralyzed patients.     

Lung mechanics following aspiration of 0.1 N hydrochloric acid

Pressure-volume curves were obtained from excised left lungs of goats at 4, 24, and 48 h after tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Air total lung capacity (TLC) at transpulmonary pressure (PL) = 35 cmH2O was 38.8 ml/kg body weight before acid, and was reduced sharply to 21.1 at 4 h, then increased to 25.6 at 24 h and 32.1 at 48 h. Excess extravascular lung water (EVLW) could account for only part of the volume reductions. Specific compliance ratio of transpulmonary pressure to total lung capacity (CL/TLC) between PL of 5 and 0 cmH2O was reduced from 0.074/cmH2O to 0.050, 0.048, and 0.053/cmH2O, respectively. Saline TLC (PL = 10 cmH2O) changed from 44.8 to 32.4, 34.3, and 45.4 ml/kg, respectively, but CL/TLC did not, suggesting airway obstruction. After injury, trapped volume at PL = 0 increased from 24.9 to 29.2, 43.3, and 37.3% TLC with air, and from 20.3 to 38.5, 33.1, and 28.5%, respectively, with saline. Air volume at a PL = 10 cmH2O on deflation fell from 82.0 to 72.1% TLC at 4 h, but was near control at 24 and 48 h. The reduction in ventilated volume was not reflected in proportionately increased shunt; therefore, some compensatory vasoconstriction must have occurred. We suggest that in affected regions increased surface forces, increased EVLW, and airway obstruction caused reductions of lung volume.     

Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology

Physiological measurements were made from anesthetized, tracheotomized, supine male ferrets. Six animals weighing 576 +/- 12 g, had tidal volumes (Vt) of 6.06 +/- 0.30 ml, respiratory frequencies (f) of 26.7 +/- 3.9 min(-1), dynamic lung compliance (CDYN) of 2.48 +/- 0.21 ml cmH2O(-1), pulmonary resistance (RL) of 22.56 +/- 1.61 cmH2O L(-1) sec. Pressure-volume curves from nine ferrets (including the above six) revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC) (89 +/- 5 ml) and functional residual capacity (FRC) (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets was about the same as in 2.5 kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) sec(-1) at 75% VC and flows of 8.4 and 5.4 VC sec(-1) at 50% and 25% VC. No particular problems were encountered in making these measurements using conventional techniques available in laboratories capable of making pulmonary function measurements on rats and guinea pigs. Preliminary studies of airways reactivity showed equal increases in pulmonary resistance in response to equivalent challenges of aerosolized carbachol and histamine. Light and electron microscopic studies showed that the airways of ferrets are even more like those of humans than are the dog's. The ease with which physiological measurements can be made and the favorable aspects of the lung anatomy indicate the ferret may be more useful, as well as less expensive, than the dog for use in studies of pulmonary physiology and inhalation toxicology.     

Lung vascular permeability changes in lambs with hyaline membrane disease

To investigate the mechanism of pulmonary edema in hyaline membrane disease (HMD), lymph from the efferent duct of the mediastinal lymph node was collected in premature lambs before and after delivery by cesarean section. Mean lymph flow in 7 lambs with histologically verified HMD increased progressively over 4 h after delivery to 3 times the fetal value, while lymph flow in 7 lambs without HMD increased to 3.5 times at 1 h and decreased thereafter. At 4 h after birth, lung lymph flow was significantly higher in lambs with HMD than in lambs without HMD (0.70 +/- 0.15 (SEM) vs 0.43 +/- 0.07 ml.h-1.kg-1). Lymph/plasma concentration ratio for small endogenous protein fractions (effective molecular radius, 3.6 and 3.8 nm) was significantly higher in lambs with HMD than in lambs without HMD at 2-4 h. Postmortem extravascular lung water was significantly higher in lambs with HMD (6.1 +/- 0.5 vs 4.3 +/- 0.3 ml/g dry lung weight). It is concluded that lung water is high in lambs with HMD, which appears to be a result both of delayed absorption of fetal lung liquid and increased permeability of the pulmonary exchange vessels.     

Effects of continuous positive airway pressure breathing on lung volume and distensibility

In this study the effects on lung elastic behavior of 10 min of breathing at a continuous positive airway pressure (CPAP) of 10 cmH2O were examined in 10 normal subjects. To investigate whether any changes were induced by release of prostaglandins, the subjects were also pretreated with the cyclooxygenase inhibitor indomethacin. CPAP produced a significant (P less than 0.001) upward shift of the pressure-volume (PV) curve [change in total lung capacity (delta TLC) 374 +/- 67 (SE) ml, mean delta volume at a transpulmonary pressure of 15 cmH2O (delta VL15) 279 +/- 31 ml] with no change in K, an index of lung distensibility. After CPAP the PV curves returned to normal base line within 20 min. The same pattern was observed after indomethacin, but the increase in TLC was significantly less (P less than 0.01) (mean delta TLC 206 +/- 42 ml) mainly because of a slight and not statistically significant increase in base-line TLC. In five subjects further PV curves with and without CPAP were obtained greater than or equal to 7 days after indomethacin. The responses were not significantly different from those obtained before indomethacin (mean delta TLC 366 +/- 89, mean delta VL15 296 +/- 42 ml). We conclude that CPAP produces an upward shift of the PV curve without a change in lung distensibility. In addition, there may be a small degree of resting alveolar duct tone that is influenced by indomethacin.