Static lung-lung interactions in unilateral emphysema.

Motivated by the introduction of single-lung transplantation into clinical practice, we compared the static mechanical properties of the respiratory system in six supine dogs before (at baseline) with those after the induction of unilateral emphysema. Relaxation volume (Vrel), total lung capacity (TLC), and static compliance of the emphysematous lung increased to 214 +/- 68, 186 +/- 39, and 253 +/- 95% (SD) of baseline, respectively. Vrel of the nonemphysematous lung fell to 81 +/- 28% of baseline, with no significant change in TLC of the nonemphysematous lung or its pressure-volume relationship, indicating that unilateral hyperinflation does not cause dropout of contralateral lung units. After unilateral emphysema, the chest wall shifted to a higher unstressed or neutral volume (when pleural pressure equals atmospheric pressure) in three of six animals, minimizing the anticipated decrease in lung recoil pressure at the higher respiratory system Vrel. The pattern of relative lung emptying in the intact dog and in the excised lungs was similar during stepwise deflations from TLC, suggesting that mean pleural pressure of the hemithoraces is equal. We conclude that in the dog the static volume distribution between emphysematous and nonemphysematous lungs is determined only by differences in lung recoil and compliance.     

Effect of increased static lung recoil on bronchial dimesions of excised lungs.

We measured bronchial diameters and lengths during static deflation and inflation in eight excised dog lobes before and after static lung recoil (Pst(L)) had been significantly increased by cooling the lobe for 48 h at 4 degrees C and ventilating it for 3 h. In control lobes, bronchial diameters were the same at any volume even though Pst(L) was different during inflation and deflation. These results agree with those of Hughes et al. (J. Appl. Physiol. 32: 25-35, 1972). However, when Pst(L) was increased, diameters at a given volume were significantly increased over control values; diameters at a given pressure were nearly the same as the controls. Therefore, under these conditions, bronchial diameter did not conform to lung volume. The ventilation process appeared to alter the circumferential elastic properties of the bronchi because diameters at all pressures were slightly larger after ventilation. Bronchial length-volume relationships were the same in both control and ventilated lobes. Thus, when Pst(L) was markedly increased, diameter corresponded best to lung recoil and length to lung volume.     

Evolution of intrathoracic airway mechanics during lung growth

Elastic recoil pressure of the lungs (Pst(L)), maximum expiratory flow rates (MEF), critical transmural pressure of the collapsible flow-limiting segment (Ptm'), and S-segment conductance (Gs) have been determined in 40 healthy subjects, 7-18 yr old. Pst(L), measured at different lung volumes (fractional) from the expiratory quasi-static pressure-volume curves, increases progressively with age. MEF's, at different lung volumes, are closely related to total lung capacity (TLC); the ratios MEF/TLC, at all lung volumes, are independent of age. Ptm' is also independence of age and body height, most values lying between 0 and -15 cmH2O; this finding suggests that the locus and the behavior of the collapsible segment do not change during growth. Gs, in absolute value, increases with growth but, when adjusted for lung size, Gs decreases steadily with age and body height. These relations suggest that, from childhood to adolescence, the air spaces grow disproportionately more than the airway system.     

Airway hysteresis in normal subjects and individuals with chronic airflow obstruction

Specific conductance (sGaw) was measured without prior pharmacological induction of bronchoconstriction before and 5-10 s after a total lung capacity (TLC) volume history in normal subjects and in individuals with chronic airflow obstruction (CAO); increased sGaw after inspiration to TLC was considered evidence of airway hysteresis. Lung elastic recoil [Pst(L)] was also measured before and after inspiration to TLC. In the normal subjects 1) prebronchodilator sGaw increased significantly, whereas Pst(L) decreased significantly after inspiration to TLC; 2) modulators of cyclooxygenase activity had no significant effects on sGaw responses to deep inspiration; and 3) airway hysteresis diminished after inhalation of atropine or metaproterenol. In the CAO group 1) prebronchodilator sGaw and Pst(L) decreased significantly after inspiration to TLC, and 2) bronchoconstriction after deep inspiration diminished after inhalation of atropine or metaproterenol. This study demonstrates that normal airways exhibit hysteresis even without alteration of resting airway tone and that airway hysteresis is impaired in CAO.     

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.     

Time dependence of airways and lung parenchymal recoil hysteresis

Hysteresis of airways and lung parenchymal recoil was examined in normal subjects by measuring specific conductance (sGaw) and lung elastic recoil (Pst,L) before and 5, 10, 15, and 30 s after deep inspiration (DI). Routine lung function tests were normal before and after inhaled metaproterenol. sGaw increased significantly for 10 s after DI. Also, sGaw(DI) was greater than sGaw in 11 of 12, 8 of 12, 7 of 12, and 6 of 12 subjects at 5, 10, 15, and 30 s, respectively, after DI. The response of sGaw to DI and metaproterenol correlated significantly with each other (r = 0.82, P less than 0.001). However, after metaproterenol, sGaw(DI) did not exceed sGaw. Pst,L decreased significantly for 15 s after DI, with the lowest measured Pst,L(DI) values occurring 5 s after DI (P less than 0.01-0.001). Both sGaw(DI) and Pst,L(DI) values returned to base line (preinspiration) in a time-dependent exponential manner, with time constants of 9.2 +/- 4.9 and 11.3 +/- 6.1 s, respectively; these time constants were not significantly different from each other. We conclude that airways hysteresis is the predominant finding in normal subjects (even without prior pharmacological bronchoconstriction) before but not after metaproterenol; Pst,L decreases after DI and, in normal individuals, returns to base line in a time-dependent manner; and the time-dependent behavior of airways and lung parenchymal hysteresis have opposite (and unequal) effects on airway caliber.     

Mechanism of reduced maximal expiratory flow with aging.

To investigate the determinants of maximal expiratory flow (MEF) with aging, 17 younger (7 men and 10 women, 39 +/- 4 yr, mean +/- SD) and 19 older (11 men and 8 women, 69 +/- 3 yr) subjects with normal pulmonary function were studied. For further comparison, we also studied 10 middle-aged men with normal lung function (54 +/- 6 yr) and 15 middle-aged men (54 +/- 7 yr) with mild chronic airflow limitation (CAL; i.e., forced expiratory volume in 1 s/forced vital capacity = 63 +/- 8%). MEF, static lung elastic recoil pressure (Pst), and the minimal pressure for maximal flow (Pcrit) were determined in a pressure-compensated, volume-displacement body plethysmograph. Values were compared at 60, 70, and 80% of total lung capacity. In the older subjects, decreases in MEF (P < 0.01) and Pcrit (P < 0.05), compared with the younger subjects, were explained mainly by loss of Pst (P < 0.05). In the CAL subjects, MEF and Pcrit were lower (P < 0.05) than in the older subjects, but Pst was similar. Thus decreases in MEF and Pcrit were greater than could be explained by the loss of Pst and appeared to be related to increased upstream resistance. These data indicate that the loss of lung recoil explains the decrease in MEF with aging subjects, but not in the mild CAL patients that we studied.     

Pressure-volume curve of lung and lobes in kittens

In the neonatal period, the incomplete aeration of the lung parenchyma and the presence of some pulmonary fluid could determine inequalities in the mechanical behavior of lung regions, favoring unevenness of ventilation distribution. We studied the pressure-volume (PV) curve of excised lungs of kittens in the 1st wk of life 1) by changing the volume a known amount and measuring the corresponding changes in transpulmonary pressure (PL) and 2) by ventilating them at a fixed PL at a rate of 20 cycles/min. An expiratory load equal to the value of PL at the resting volume of the respiratory system was added to avoid the collapse of the lung. A lobar bronchus was then tied, and the measurements were repeated. The difference in PV curves before and after ligature therefore represented the PV curve of the lobe. This was done for all the lobes (upper and middle right, lower right, lower left, upper left) in a random order. A total of 20 lungs and 61 lobes have been studied. Individual lobes were not different in terms of dry-to-wet weight ratio, compliance per unit weight, or per maximal volume and shape of the PV curve, indicating a similar mechanical behavior. Dynamic lung compliance averaged 76% +/- 15 SD of the static value, suggesting some degree of asynchronous behavior of lung regions or viscoelastic properties of the tissue.     

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.     

Lung structure parameters estimated from modeling aerosol deposition in isolated dog lungs

A three-compartment model predicting the recovery of aerosol boli (i.e., the ratio of the number of particles expired to the number inspired) as a function of breath-holding time and bolus penetration was fitted to experimental data measured in nine isolated dog lungs. For each lung, the diameters of alveoli and alveolar ducts, as well as the volume fractions of alveoli, alveolar ducts, and airways, were determined as parameters providing the best fit. Parameter values were alveolar diameter = 0.116 +/- 0.007 (SE) mm, alveolar duct diameter = 0.284 +/- 0.015 mm, total alveolar volume/total lung capacity (TLC) = 0.68 +/- 0.02, total alveolar duct volume/TLC = 0.24 +/- 0.02, and total airway volume/TLC = 0.09 +/- 0.01. These values agreed with published values for linear dimensions and volumetric fractions in the canine lung. The mean alveolar diameter determined by the model in the nine lungs agreed closely with a mean value of 0.115 +/- 0.002 mm determined by morphometric analysis of photographs of the subpleural alveoli in the same lungs. The procedure of fitting the model to experimental data appears to have promise as a noninvasive probe of the lung periphery. However, aerosol-derived dimensions were more variable than morphometric ones, possibly because of interlung differences in aerosol distribution not accounted for in the model.     

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.     

Inspiratory muscles during exercise: a problem of supply and demand

The capacity of inspiratory muscles to generate esophageal pressure at several lung volumes from functional residual capacity (FRC) to total lung capacity (TLC) and several flow rates from zero to maximal flow was measured in five normal subjects. Static capacity was 126 +/- 14.6 cmH2O at FRC, remained unchanged between 30 and 55% TLC, and decreased to 40 +/- 6.8 cmH2O at TLC. Dynamic capacity declined by a further 5.0 +/- 0.35% from the static pressure at any given lung volume for every liter per second increase in inspiratory flow. The subjects underwent progressive incremental exercise to maximum power and achieved 1,800 +/- 45 kpm/min and maximum O2 uptake of 3,518 +/- 222 ml/min. During exercise peak esophageal pressure increased from 9.4 +/- 1.81 to 38.2 +/- 5.70 cmH2O and end-inspiratory esophageal pressure increased from 7.8 +/- 0.52 to 22.5 +/- 2.03 cmH2O from rest to maximum exercise. Because the estimated capacity available to meet these demands is critically dependent on end-inspiratory lung volume, the changes in lung volume during exercise were measured in three of the subjects using He dilution. End-expiratory volume was 52.3 +/- 2.42% TLC at rest and 38.5 +/- 0.79% TLC at maximum exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effect of distortion on the mechanical properties of newborn piglet lung

During breathing the relatively high chest wall-to-lung compliance ratio of the newborn favors distortion of the respiratory system. In this study we have examined the effect of lung deformation, generated by a hydrostatic pleural surface pressure gradient, on the static (Cstat) and dynamic (Cdyn) compliance of the isolated newborn piglet lung. Seven lungs from piglets 2-7 days old have been studied in a saline-filled plethysmograph. Static pressure-volume (PV) curves were obtained by changing the volume a known amount and measuring the corresponding changes in transpulmonary pressure. Dynamic PV curves were obtained by ventilating the lung at a fixed pressure and at 20 cycles/min. These experiments were repeated in an air plethysmograph on the undeformed lung. Lung volume history was standardized prior to each maneuver by three inflations to 20-25 cmH2O. Lung collapse was avoided by applying an end-expiratory load equal to the transpulmonary pressure at functional residual capacity. Cstat was not significantly different between the deformed and undeformed lung (P greater than 0.05). Cdyn was less than Cstat in both cases (P less than 0.025) and was reduced further by deformation (P less than 0.05). We conclude that 1) peripheral airway obstruction or the viscoelastic properties of the piglet lung, or both, decrease Cdyn, and 2) deformation increases the external (PV) respiratory work by further decreasing Cdyn.     

The impact of aging and habitual physical activity on static respiratory work at rest and during exercise

We investigated the effects of aging on the elastic properties of lung tissue and the chest wall, simultaneously quantifying the contribution of each component to static inspiratory muscle work in resting and exercising adults. We further evaluated the interaction of aging and habitual physical activity on respiratory mechanics. Static lung volumes and elastic properties of the lung and chest wall (pressure-volume relaxation maneuvers) in 29 chronically sedentary and 29 habitually active subjects, grouped by age, were investigated: young (Y, 20-30 years), middle-aged (M, 40-50 years), and older (O, >60 years). Using static pressure-volume data, we computed the elastic work of breathing (joules per liter, J.l(-1)), including inspiratory muscle work, over resting and exercising tidal volume excursions. Elastic work of the lung (Y = 0.79 +/- 0.05; M = 0.47 +/- 0.05; O = 0.43 +/- 0.05 J.l(-1)) and chest wall (Y = -0.49 +/- 0.06; M = -0.12 +/- 0.07; O = 0.04 +/- 0.05 J.l(-1) ) changed significantly with age (P < 0.05). With aging, a parallel displacement of the chest wall pressure-volume curve resulted in a shift from energy being stored primarily during expiration to energy storage during inspiration, and driving expiration, both at rest and during exercise. Although deviating significantly from young adults, this did not significantly elevate static inspiratory muscle work but resulted in a redistribution of the tissues on which this work was performed and the phase of the respiratory cycle in which it occurred. Nevertheless, static inspiratory muscle work remained similar across age groups, at rest and during exercise, and habitual physical activity failed to influence these changes.     

Frequency-dependent effects of hypercapnia on respiratory mechanics of cats

The effect of increasing arterial partial pressure of CO2 (PaCO2) on respiratory mechanics was investigated in six anesthetized, paralyzed cats ventilated by constant-flow inflation. Respiratory mechanics were studied after end-inspiratory occlusions. Zero frequency resistance (Rmax), infinite frequency resistance (Rmin), and static elastance (Est) were calculated for the respiratory system, lung, and chest wall. Alveolar ventilation was manipulated by the addition of dead space to achieve a range of PaCO2 values of 29.3-87.3 mmHg. Cats did not become hypoxic during the experiment. Under control conditions marked frequency dependence in Rmax, Rmin, and Est of the respiratory system, lungs, and chest wall was demonstrated. The chest wall contributed 50% of the total resistance of the respiratory system. With increasing PaCO2 the only resistance observed to increase was Rmax of the lung (P less than 0.01). There were also no changes in the static elastic properties of either the lungs or the chest wall. These results suggest that hypercapnia increases resistance by changes in the lung periphery and not in the conducting airways.     

Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships

To determine alveolar pressure-volume relationships, alveolar three-dimensional reconstructions were prepared from lungs fixed by vascular perfusion at various points on the pressure-volume curve. Lungs from male Sprague-Dawley rats were fixed by perfusion through the pulmonary artery following a pressure-volume maneuver to the desired pressure point on either the inflation or deflation curve. Tissue samples from lungs were serially sectioned for determination of the volume fraction of alveoli and alveolar ducts and reconstruction of alveoli. Alveoli from lungs fixed at 5 cmH2O on the deflation curve (approximating functional residual volume) had a volume of 173 X 10(3) microns3, a surface area of 11,529 microns2, a mouth opening diameter of 72.7 microns, and a mean caliper diameter of 91.8 micron (SE). Alveolar shape changes during deflation from total lung capacity to residual volume was first (30 to 10 cmH2O) associated with little change in the diameter of the alveoli (102.7 +/- 2.4 to 100.3 +/- 3.3 microns). In the range overlapping normal breathing (10 to 0 cmH2O) there was a substantial decrease in diameter (100.3 +/- 3.3 to 43.3 +/- 2.3 microns). These measurements and others made on the relative changes in the dimensions of the alveolus suggest that the elastic network, particularly around the alveolar ducts, are predominant in determining lung behavior near the volume expansion limits of the lung while the elastic and surface tension properties of the alveoli are predominant in the volume range around functional residual capacity.     

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.     

Effects of unilateral hyperinflation on the interpulmonary distribution of pleural pressure.

Motivated by single lung transplantation, we studied the mechanics of the chest wall during single lung inflations in recumbent dogs and baboons and determined how pleural pressure (Ppl) is coupled between the hemithoraces. In one set of experiments, the distribution of Ppl was inferred from known volumes and elastic properties of each lung. In a second set of experiments, costal pleural liquid pressure (Pplcos) was measured with rib capsules. Both methods revealed that the increase in Ppl over the ipsilateral or inflated lung (delta Ppli) is greater than that over the contralateral or noninflated lung (delta Pplc). Mean d(delta Pplc)/d(delta Ppli) and its 95% confidence interval was 0.7 +/- 0.1 in dogs and 0.5 +/- 0.1 in baboons. In a third set of experiments in three dogs and three baboons, we prevented sternal displacement and exposed the abdominal diaphragm to atmospheric pressure during unilateral lung inflation. These interventions had no significant effect on Ppl coupling between the hemithoraces. We conclude that lungs of unequal size and mechanical properties need not be exposed to the same surface pressure, because thoracic midline structures and the lungs themselves resist displacement and deformation.