Effects of starvation on lung mechanics and biochemistry in young and old rats

Two groups of rats (young and old) were food-deprived for 3 wk and were compared with age-matched fed groups. Final body weight and dry and wet weights of lungs were significantly reduced in both young and old starved rats. As determined by saline volume-pressure (VP) curves, lungs of young starved rats accepted significantly less volume at all pressure levels compared with lungs of young fed rats. When expressed as a percent of maximum lung volume, the VP curve in young starved rats was significantly shifted upward at low lung volumes. In the old rats, the VP curves were similar in fed and starved rats. Total lung content of protein, DNA, crude connective tissue, hydroxyproline, and elastin were significantly reduced in young starved compared with young fed rats, whereas in old starved rats only protein and DNA contents were lower than those in old fed animals. It appears that in rapidly growing young rats starvation leads to growth retardation, loss of connective tissue components, and possibly reduction in tissue elastic forces at low lung volumes, whereas starvation has no significant effects on lung mechanics and connective tissue in old rats.     

Respiratory mechanics and maximal expiratory flow in the anesthetized mouse.

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 +/- 0.04 and 0.25 +/- 0.01 ml, respectively, in 20 mice weighing 22.2 +/- 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cm H(2)O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.     

Pulmonary function changes in ozone-interaction of concentration and ventilation.

A total of 28 healthy young subjects have been exposed for 2 h to ozone (0.37-0.75 ppm) under conditions of either rest or intermittent light exercise (sufficient to increase the respiratory minute volume by a factor of 2.5). All pulmonary function tests (vital capacity, forced expiratory volume, maximum expiratory flow-volume curve, slope of phase III of alveolar nitrogen plateau) showed a significant deterioration relative to parallel control experiments. Responses were related to the dose of ozone as calculated from the product of concentration, exposure time, and respiratory minute volume during exposure, changes at 1 h averaging approximately one-half those seen at 2 h.     

Maximum expiratory flow-volume curves during short periods of microgravity

To elucidate the effect of normal gravitation on the shape of the maximum expiratory flow-volume (MEFV) curve, we studied nine normal subjects in a National Aeronautics and Space Administration microgravity research aircraft. They performed multiple MEFV maneuvers at 0, 1, and approximately 2 G. The MEFV curves for each subject were filtered, aligned at residual volume, and ensemble averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the forced vital capacity at 0 G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0 G over about the upper half of the vital capacity. This is similar to the change previously reported during headout immersion and is consistent with the known effect of engorgement of the lung with blood on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points that determine the detailed individual configuration of MEFV curves can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and thus wave speed.     

Changes in mechanics of breathing during experimental cough and sneeze in anaesthetized cats

Pleural pressure, airflow and tidal volume during experimental cough and sneeze elicited by mechanical stimulation of the tracheobronchial and nasal mucous membranes were investigated in fifty anaesthetized cats (pentobarbital, 40 mg/kg i.p.). Pressure-volume, pressure-flow and flow-volume relations were studied during these expulsive processes. In comparison to quiet breathing there was a decrease in dynamic lung compliance in both respiratory tract reflexes (p less than 0.001), especially in their expiratory phases. As compared to quiet breathing, the total work of breathing was significantly increased (p less than 0.001) in cough (20 times) as well as in sneeze (13 times). The total lung resistance increased markedly (p less than 0.001) in both cough and sneeze compared to quiet breathing. In these expulsive processes there was also a high "cough index" (resistance calculated from the peak flow and instantaneous pressure). The flow-volume curve in cough, in contradistinction to sneeze, indicated a significantly reduced airflow of the end of expiration (at 85% of the expired volume), demonstrating a concomitant bronchoconstriction.     

Expiratory pattern of newborn mammals

The passive mechanical time constant (tau pass) of the respiratory system is relatively similar among newborn mammalian species, approximately 0.15-0.2 s. However, breathing rate (f) is higher in smaller species than larger species in order to accommodate the relatively larger metabolic demands. Since tidal volume per kilogram is an interspecies constant, in the fastest breathing species the short expiratory time should determine a substantial dynamic elevation of the functional residual capacity (FRC). We examined the possibility of a difference in expiratory time constant between dynamic and passive conditions by analyzing the expiratory flow pattern of nine newborn unanesthetized species during resting breathing. In most newborns the late portion of the expiratory flow-volume curve was linear, suggesting muscle relaxation. The slope of the curve, which represents the dynamic expiratory time constant of the respiratory system (tau exp), varied considerably among animals (from 0.1 to 0.7 s), being directly related to the inspiratory time and inversely proportional to f. In relatively slow-breathing newborns, such as infants and piglets, tau exp is longer than tau pass most likely due to an increase in the expiratory laryngeal resistance and FRC is substantially elevated. On the contrary, in the fastest breathing newborns (such as rats and mice) tau exp is similar or even less than tau pass, because at these high rates dynamic lung compliance is lower than its passive value and the dynamic elevation of FRC is small. In dynamic conditions, therefore, the product of tau exp and f is maintained within narrow limits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary functions of rats trained with mild exercise

The purpose of the present study was to determine if lung function is modified by physical exercise in male and female rats. The animals were subjected to a running program for 5 weeks. At the termination of the program period, the running rats (R) had body weight smaller than the sedentary control rats (S). In male rats, the weights of lung, heart and adrenal glands, which were corrected with body weight, were larger in the R than in the S, and the absolute weight of adrenal glands also increased in the R. The rates of peak flow and maximum expiratory flow at 50% total lung capacity, which were corrected with either body weight, lung weight or total lung capacity, increased in the R. Because of no significant change in the flow resistance and compliance of the lungs, the increases in the rates of these expiratory flows might have been due to increased airway rigidity caused by some mechanisms relating to exercise stimuli. In female rats, on the other hand, the above changes in the R were little or less.     

Volume infusion produces abdominal distension, lung compression, and chest wall stiffening in pigs.

The effect of severe generalized edema on respiratory system mechanics is not well described. We measured airway pressure, gastric pressure, and four vertical pleural pressures in 13 anesthetized paralyzed pigs ventilated in the upright position. Pressure-volume relationships of the respiratory system, chest wall, and lung were measured on deflation from total lung capacity to residual volume and during tidal breathing both before (control) and 50 min after one of two interventions. In one series of experiments, a volume equal to 15-20% of the pig's body weight was infused intravenously. In a second series, a balloon was placed in the peritoneal space to distend the abdomen to the same gastric pressures as achieved in the first series. Measurements were compared before and after either abdominal balloon inflation or volume infusion. Volume infusion increased the pleural pressure in dependent lung regions, decreased both total lung capacity (34%) and functional residual capacity (62%) (both P less than 0.05), and markedly shifted the respiratory system and chest wall pressure-volume curves to the right, but it only moderately affected the lung deflation curve. Tidal compliances of the respiratory system, chest wall, and lung decreased 36, 31, and 49%, respectively (all P less than 0.05). The effect of abdominal balloon inflation on respiratory system mechanics was similar to that of volume infusion. We conclude that infusing large volumes of fluid markedly alters chest wall mechanics, mainly by causing abdominal distension that prohibits descent of the diaphragm.     

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.     

Decrease in Ventilatory Capacity between Ages of 50 and 54 in Representative Sample of Swedish Men

The ventilatory capacity, including flow-volume curves of 313 men, all 50 years old, was examined in 1963 and 1967. The group as a whole, which included persons with chronic bronchitis, with “other respiratory symptoms,” and without respiratory symptoms, showed the same absolute decrease in ventilatory capacity.Vital capacity, forced expiratory volume, and maximum expiratory flow all dropped more for the smokers than for either the non-smokers or the ex-smokers. In those who had stopped smoking for four years or less, however, ventilatory capacity did not decline significantly less than in those who continued to smoke.     

Novel method for measuring effects of gas compression on expiratory flow

During forced vital capacity maneuvers in subjects with expiratory flow limitation, lung volume decreases during expiration both by air flowing out of the lung (i.e., exhaled volume) and by compression of gas within the thorax. As a result, a flow-volume loop generated by using exhaled volume is not representative of the actual flow-volume relationship. We present a novel method to take into account the effects of gas compression on flow and volume in the first second of a forced expiratory maneuver (FEV(1)). In addition to oral and esophageal pressures, we measured flow and volume simultaneously using a volume-displacement plethysmograph and a pneumotachograph in normal subjects and patients with expiratory flow limitation. Expiratory flow vs. plethysmograph volume signals was used to generate a flow-volume loop. Specialized software was developed to estimate FEV(1) corrected for gas compression (NFEV(1)). We measured reproducibility of NFEV(1) in repeated maneuvers within the same session and over a 6-mo interval in patients with chronic obstructive pulmonary disease. Our results demonstrate that NFEV(1) significantly correlated with FEV(1), peak expiratory flow, lung expiratory resistance, and total lung capacity. During intrasession, maneuvers with the highest and lowest FEV(1) showed significant statistical difference in mean FEV(1) (P < 0.005), whereas NFEV(1) from the same maneuvers were not significantly different from each other (P > 0.05). Furthermore, variability of NFEV(1) measurements over 6 mo was <5%. We concluded that our method reliably measures the effect of gas compression on expiratory flow.     

Respiratory Function in Healthy Taiwanese Infants: Tidal Breathing Analysis,Passive Mechanics,and Tidal Forced Expiration

Background

Although infant lung function (ILF) testing is widely practiced in developed Western countries it is not typically performed in Eastern countries, and lung measurements are scarce for Asian infants. Therefore, this study aimed to establish normal reference values for Taiwanese infants.

Materials and Methods

Full-term infants without any chronic diseases and major anomalies were enrolled in the Prediction of Allergies in Taiwanese Children (PATCH) cohort study. Detailed medical data, such as body weight and length, birth history, and histories of previous illness and hospitalization were recorded. Lung function measurements such as analysis of tidal breathing, passive respiratory mechanics, and forced tidal expiratory flow-volume curves were obtained through Jaeger Masterscreen BabyBody Paediatrics System. Multiple linear analyses were performed to determine various parameters of the lung function tests.

Results

ILF test parameters were collected from 126 infants, and 189 tests were performed. The results revealed that the ratio of time to peak expiratory flow to total expiratory time, the ratio of volume to peak expiratory flow to total expiratory volume, and the ratio of inspiratory time to total respiratory time remained relatively constant despite differences in age. However, body length is the strongest independent variable influencing tidal volume, respiratory rate, resistance, compliance, and maximal expiratory flow at functional residual capacity.

Conclusion

According to our review of relevant literature, this is the first study to establish a reference data of ILF tests in the Asian population. This study provided reference values and regression equations for several variables of lung function measurements in healthy infants aged less than 2 years. With these race-specific reference data, ILF can more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity.     

Heterogeneous lung emptying during forced expiration

Several lines of evidence suggest that the healthy mammalian lung empties homogeneously during a maximally forced deflation. Nonetheless, such behavior would appear to be implausible if for no other reason than that airway structure is known to be substantially heterogeneous among parallel pathways of gas conduction. To resolve this paradox we reexamined the degree to which lung emptying is homogeneous, and considered mechanisms that might control differential regional emptying. Twelve excised canine lungs were studied. Regional alveolar pressure relative to pleural pressure was used as an index of regional lung volume. By use of a capsule technique, alveolar pressure was measured simultaneously in each of six regions during flow-limited deflations; flow from the lung was measured plethysmographically. The standard deviation of interregional pressure differences, which was taken as an index of nonuniformity, was 0.0, 0.74, 0.64, and 0.90 cmH2O at mean recoil pressures of 30, 8.4, 4.5, and 2.1 cmH2O (0, 25, 50, and 75% expired vital capacity), indicating that interregional pressure differences increased more rapidly earlier in the deflation. When we examined the time rate of change of regional alveolar pressure as an index of regional flow, we observed an intricate pattern of differential regional behavior that was inapparent in the maximum expiratory flow-volume (MEFV) curve. The most plausible interpretation of these findings is that regions of the healthy excised canine lung empty heterogeneously to a small degree, but in an interdependent compensatory pattern that is inapparent in the configuration of the maximum expiratory flow-volume curve.     

Role of expiratory flow limitation in determining lung volumes and ventilation during exercise.

We determined the role of expiratory flow limitation (EFL) on the ventilatory response to heavy exercise in six trained male cyclists [maximal O2 uptake = 65 +/- 8 (range 55-74) ml. kg-1. min-1] with normal lung function. Each subject completed four progressive cycle ergometer tests to exhaustion in random order: two trials while breathing N2O2 (26% O2-balance N2), one with and one without added dead space, and two trials while breathing HeO2 (26% O2-balance He), one with and one without added dead space. EFL was defined by the proximity of the tidal to the maximal flow-volume loop. With N2O2 during heavy and maximal exercise, 1) EFL was present in all six subjects during heavy [19 +/- 2% of tidal volume (VT) intersected the maximal flow-volume loop] and maximal exercise (43 +/- 8% of VT), 2) the slopes of the ventilation (DeltaVE) and peak esophageal pressure responses to added dead space (e.g., DeltaVE/DeltaPETCO2, where PETCO2 is end-tidal PCO2) were reduced relative to submaximal exercise, 3) end-expiratory lung volume (EELV) increased and end-inspiratory lung volume reached a plateau at 88-91% of total lung capacity, and 4) VT reached a plateau and then fell as work rate increased. With HeO2 (compared with N2O2) breathing during heavy and maximal exercise, 1) HeO2 increased maximal flow rates (from 20 to 38%) throughout the range of vital capacity, which reduced EFL in all subjects during tidal breathing, 2) the gains of the ventilatory and inspiratory esophageal pressure responses to added dead space increased over those during room air breathing and were similar at all exercise intensities, 3) EELV was lower and end-inspiratory lung volume remained near 90% of total lung capacity, and 4) VT was increased relative to room air breathing. We conclude that EFL or even impending EFL during heavy and maximal exercise and with added dead space in fit subjects causes EELV to increase, reduces the VT, and constrains the increase in respiratory motor output and ventilation.     

Postnatal lung function in the developing rat.

Little is known about lung function during early stages of postnatal maturation, although the complex structural changes associated with developing rat lung are well studied. We therefore analyzed corresponding functional (lung volume, respiratory mechanics, intrapulmonary gas mixing, and gas exchange) and structural (alveolar surface area, mean linear intercept length, and alveolar septal thickness) changes of the developing rat lung at 7-90 days. Total lung capacity (TLC) increased from 1.54 +/- 0.07 to 16.7 +/- 2.46 (SD) ml in proportion to body weight, but an increase in body weight exceeded an increase in lung volume by almost twofold. Series dead space volume increased from 0.21 +/- 0.03 to 1.38 +/- 0.08 ml but decreased relative to TLC from 14% to 8%, indicating that parenchymal growth exceeded growth of conducting airways. Diffusing capacity of CO (D(CO)) increased from 8.1 +/- 0.8 to 214.1 +/- 23.5 micromol min(-1) hPa(-1), corresponding to a substantial increase in surface area from 744 +/- 20 to 6,536 +/- 488 cm(2). D(CO) per unit of lung volume is considerably lower in the immature lung, inasmuch as D(CO)/TLC in 7-day-old rats was only 42% of that in adult (90 day-old) rats. In humans, however, infants and adults show comparable specific D(CO). Our functional and structural analysis shows that gas exchange is limited in the immature rat lung. The pivotal step for improvement of gas exchange occurs with the transition from bulk alveolarization to the phase of expansion of air spaces with septal reconstruction and microvascular maturation.     

Effects of semi-starvation on the total body composition and absorptive function of the small intestine of the young adult female rat.

Sixteen female rats aged about 80 days and with a mean body weight of 175 g were fed 40% of their ad libitum intake of a laboratory chow. They were killed and analysed for water, protein, lipid and ash after 9, 21-5, 30-2 and 38-8% of body weight had been lost. Compared to a control group of four animals, the 38-8% group lost 13 g or 34% of their protein. The animals in the 21-5, 30-2 and 38-8% groups lost 7-5 g or 87% of their lipid leaving only 1-1 g of lipid. The percentage protein in the body was little affected by body weight loss but lipid decreased from 5 to 1%. In another experiment with 26 rats of 205 g mean body weight and aged about 115 days, absorption rates by the small intestine were measured in vivo after variable weight losses between 0 and 39%. D(+)-Glucose uptake was increased by about 70% in those animals which had lost only 5% of body weight and this increased uptake was retained in those rats which had lost up to 39% of body weight. The absorption of L-leucine was not affected by the decline in body weight compared to the controls but relative to body weight, the ability of the intestine to absorb increased. In the same animals, the wet and dry weights of the small intestine declined slightly faster than body weight and the length of the small intestine tended to decrease slightly with increasing loss of body weight.     

Heterogeneous airway tone in asthmatic subjects.

We examined the effect of volume history on the dynamic relationship between airways and lung parenchyma (relative hysteresis) in 20 asthmatic subjects. The acoustic reflection technique was employed to evaluate changes in airway cross-sectional areas during a slow continuous expiration from total lung capacity to residual volume and inspiration back to total lung capacity. Lung volume was measured continuously during this quasi-static maneuver. We studied three anatomic airway segments: extra- and intrathoracic tracheal and main bronchial segments. Plots of airway area vs. lung volume were obtained for each segment to assess the relative magnitude and direction of the airway and parenchymal hysteresis. We also performed maximal expiratory flow-volume and partial expiratory flow-volume curves and calculated the ratio of maximal to partial flow rates (M/P) at 30% of the vital capacity. We found that 10 subjects (group I) showed a significant predominance of airway over parenchymal hysteresis (P < 0.005) at the extra- and intrathoracic tracheal and main bronchial segments; these subjects had high M/P ratios [1.53 +/- 0.27 (SD)]. The other 10 subjects (group II) showed similar airway and parenchymal hysteresis for all three segments and significantly lower M/P ratios (1.16 +/- 0.20, P < 0.01). We conclude that the effect of volume history on the relative hysteresis of airway and lung parenchyma and M/P ratio at 30% of vital capacity in nonprovoked asthmatic subjects is variable. We suggest that our findings may result from heterogeneous airway tone in asthmatic subjects.     

Dietary vitamin E and the effects of inhaled nitrogen dioxide on rat lungs.

Groups of rats were fed diets containing supplemented adequate, or deficient amounts of alpha-tocopherol. Some rats from each group were exposed for 2 h to high-level concentrations of nitrogen dioxide in their breathing air. A comparison of wet and dry lung weights did not indicate that exposure of the gas was a cause of edema. Proportion of lung weight to total body weight was increased in all animals with the lipid content diminishing according to the amount of dietary apha-tocopherol available. Dietary intake of the vitamin did not seem to protect the lipid content of lungs of the supplemented dietary group from oxidation. No difference in total peroxides was noted between any of the groups. Inflation and deflation compliance measurements were greater for both exposed and non-exposed supplemented animals when compared to the adequate and deficient groups.     

Determinants of transdiaphragmatic pressure in dogs

We measured the transdiaphragmatic pressure (Pdi) during bilateral phrenic nerve stimulation and evaluated the determinants of its change with lung volume, chest wall geometry, and respiratory system impedance in supine dogs. Four rows of radiopaque markers were sewn onto muscle bundles of the costal and crural diaphragm between their origin on the central tendon and their insertion on the rib cage and spine. The length of the diaphragm (L) was determined from the projection images of marker rows using biplane fluoroscopy. Measurements were made at lung volumes between total lung capacity and functional residual capacity before and after the infusion of Ringer lactate solution into the abdominal cavity. In contrast to relaxation, during tetanic stimulation the active lengths of the muscle bundles were similar at all volumes, but the diaphragm assumed different shapes. Although the small differences in active muscle length with volume and liquid loads are consistent with only small changes in muscle force output, Pdi varied by a factor of greater than or equal to 5. There was no single L/Pdi curve that fitted all data during 50-Hz stimulations. We conclude that under these experimental conditions Pdi is not a unique measure of the force produced by the diaphragm and that lung volume, chest wall geometry, and respiratory system impedance are important determinants of the mechanical efficiency of the diaphragm as a pressure generator.     

Respiratory measurements of unsedated small laboratory mammals using nonrebreathing valves

The respiratory frequency, tidal volume, minute volume, oxygen uptake and carbon dioxide output of unsedated hamsters, rats, guinea pigs and rabbits were measured to obtain comparative data and to evaluate the performance of those species as unsedated subjects. The animals were trained to remain stationary and breathe through nonrebreathing valves while expired gas was collected and respiratory frequency was monitored. Measurements of dogs also were conducted to obtained comparative data by similar methods. Hamsters were readily trained and performed reliably during repeated trials. Rats and guinea pigs were more difficult to train and performed erratically. The rabbits' performance was intermediate between that of hamsters and the other species. The back pressures caused by the small animal nonrebreathing valves at estimated peak flow rates were either similar to or less than those encountered by dogs. Measured respiratory values were compared to values predicted by published equations based on body weight. Data from this study generally reflected species differences related to body weight and metabolic rate similar to those predicted by the equations, but values from the four smaller species also may have reflected differences related to behavior.