Altered Lung Mechanics Research Articles

Respiratory Acoustic Impedance in Left Ventricular Failure

The measurement of respiratory acoustic impedance (Zrs) by forced pseudorandom noise provides a simple means of assessing respiratory mechanics in nonintubated intensive care patients. To characterize the lung mechanical alterations induced by acute vascular congestion of the lung, Zrs was measured in 14 spontaneously breathing patients hospitalized for acute left ventricular failure. The Zrs data in the cardiac patients were compared with those of 48 semirecumbent normal subjects and those of 23 sitting asthmatic patients during allergen-induced bronchospasm. In the patients with acute left ventricular failure, the Zrs abnormalities noted were an excessive frequency dependence of resistance from 10 to 20 Hz and an abnormally low reactance at all frequencies, abnormalities qualitatively similar to those observed in the asthmatic patients but of lesser magnitude. Acute lung vascular congestion modifies the acoustic impedance of the respiratory system. Reflex-induced bronchospasm might be the main mechanism altering respiratory acoustic impedance in acute left ventricular failure.

Mild isocapnic hypoxia enhances the bronchial response to methacholine in asthmatic subjects.

We studied the effect of mild isocapnic hypoxia (FIO2 = 15.5%) on lung mechanics, heart rate, circulating plasma catecholamines, and bronchial responsiveness to methacholine in ten asthmatic adults. Hypoxia did not alter lung mechanics (i.e., dynamic pulmonary compliance [CLdyn], pulmonary resistance [RL]) nor did it increase plasma catecholamines, but it significantly increased bronchial responsiveness to aerosolized methacholine, as assessed by the fall in forced expiratory volume in one second (FEV1: 1.2 +/- 0.18 versus 0.9 +/- 0.14 L/s, p less than 0.05), the rise in RL (RL: 19.1 +/- 1.4 versus 8.4 +/- 1 cm H2O/L/s, p less than 0.05), and the steeper slope of the dose-response curve to methacholine. We concluded that the hypoxic characteristic of asthmatic attacks may aggravate airflow obstruction.

The mechanical effects of expiratory airflow limitation on cardiac performance in cystic fibrosis.

The influence of altered lung mechanics on cardiac performance in cystic fibrosis (CF) was examined in an analysis of cardiorespiratory performance during exercise. The stroke volume (SV) response to exercise, derived from an indirect Fick (CO2) determination of cardiac output during submaximal steady-state exercise served as the index of cardiac performance. The relationship between exercising SV and forced expiratory volume in one second (FEV1), inspiratory duty cycle during exercise (Tl/Ttot) and exercising systemic arterial oxygen tension (PaO2) was examined in 15 studies involving 11 individuals with CF. The subjects were 12 to 25 yr of age and the FEV1 ranged from 15 to 72% predicted. Although a relationship existed between the SV expressed as a percentage of the mean predicted from height and gender (SV%) and PaO2 (r = 0.61, p less than 0.02), a more striking relationship was noted between SV% and either FEV1 or Tl/Ttot (r = 0.79 and 0.73, p less than 0.002). A multiple regression analysis of SV% identified an element of the relationship between FEV1 or Tl/Ttot and cardiac performance which was distinct from the influence of the coexisting hypoxia (p less than or equal to 0.05). The limitation in the SV response to exercise was noted to be in part reversible, coincident with an improvement in ventilatory mechanics that had occurred in 2 of the 4 persons in whom repeated studies were available. These observations suggest that in individuals with CF and a moderately severe degree of expiratory airflow limitation, there is a mechanical element of cardiopulmonary interdependence.

Alteration of lung mechanics by protein-calorie malnutrition in weaned rats

The influence of protein-calorie malnutrition on lung development was studied in weaned rats. From the age of 28 days, they received ad libitum a diet containing 15 or 5% proteins (P15 or P5) or half of the high-protein diet ( 1 2 P15 ). After one month, lung weight and lung protein and DNA content were decreased in test animals, but DNA concentration was increased. These lungs appeared to have a higher density of smaller cells. V-P curves were performed on excised lungs. With air-filling, the curves obtained in 1 2 P15 and P5 rats weree shifted downward and to the right even when expressed as percent of maximal volume. Their exponential analysis assessed the decreased in compliance. With saline-filling, V-P curves were similarly shifted except at low volumes. Both in P5 and 1 2 P15 rats, the pressure at lung rupture after air- or saline-filling was increased. In conclusion, protein-calorie malnutrition started after weaning interferes with lung development, causing an increase in surface and tissue elastic forces and in resistance to rupture.

Increased synthesis of elastin in amiodarone-induced pulmonary fibrosis.

Both synthesis and total content of lung elastin were measured after induction of interstitial pulmonary fibrosis in hamsters by a single intratracheal insufflation of amiodarone. Elastin synthesis, as measured by 14C-lysine incorporation into desmosine and isodesmosine, was significantly elevated (P less than 0.05) above control values for a 3-week interval after induction of lung injury. Total lung elastin content in the amiodarone-treated animals was 32% greater than in controls (P less than 0.05) 2 weeks after insufflation of the agent. Furthermore, the time course of elastin synthesis in this experimental model was similar to that observed in bleomycin-induced pulmonary fibrosis in hamsters. Increases in elastin may therefore be a common feature of interstitial pulmonary fibrosis and may contribute to the altered lung mechanics seen in this disease.

Linear-lumped-parameter modeling of pulmonary impedance in monkeys.

Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linear-lumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr approximately 19%). Networks consisting of two series RIC pathways in parallel resulted in a lower Dr (approximately 14%), but parameter values were difficult to interpret. Despite not modeling the decrease in RL with frequency below 8 Hz, an airway wall compliance, Caw, network in which the airways were separated into central and peripheral components resulted in an even lower Dr (approximately 11%). In addition, parameter values were easy to interpret, consistent among our "normal" monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that networks containing both parallel pathways and Caw are necessary to model ZL over the entire frequency range (2-32 Hz), the effect of Caw is an important determinant of ZL above 8 Hz, and a six-parameter Caw network with the ratio of Caw to parenchymal compliance, Cp, fixed may prove useful in interpreting changes in ZL induced by alterations in lung mechanics in monkeys.

Respiratory mechanics in men following a deep air dive.

The mechanical properties of the lungs were measured in 10 men before and after a simulated air dive to 285 ft of seawater (87 m). The objective was to determine whether a dive likely to produce pulmonary bubble emboli would alter lung mechanics. Lung function was measured predive and at 1, 2, 3, 6, 7, and 23 h postdive. Measurements of lung function were also made at identical times on a control day when no dive was made. Each set of measurements included precordial Doppler signals, pulmonary resistance, quasistatic lung compliance, forced vital capacity (FVC), forced expired volume after 1.0 s (FEV 1.0), the ratio of FEV 1.0 to FVC (FEV 1.0/FVC%), and maximal airflow after 50 and 75% of the vital capacity had been expired (Vmax50 and Vmax75, respectively). Base-line measurements of pulmonary resistance and quasistatic compliance were normal in all subjects. FVC and FEV 1.0 were greater than predicted for most subjects and were increased proportionately so that the FEV 1.0/FVC% was normal. Following the dive, bubble signals were heard in four subjects, and two subjects had mild symptoms of decompression sickness. No subject demonstrated any alteration in lung function that could be attributed to the dive. We concluded that stressful decompressions capable of producing "silent" pulmonary bubble emboli do not alter lung mechanics.

Respiratory system impedance in patients with acute left ventricular failure: pathophysiology and clinical interest.

To investigate the relationship between alterations in lung mechanics and acute pulmonary vascular congestion, repeated measurements of the respiratory system impedance (Zrs) were performed in 11 patients with and in seven without acute left ventricular failure. Indexes of Zrs were obtained by calculating the average and slope of the resistance and reactance in low (10 to 20 Hz) and high (20 to 50 Hz) frequency intervals. Zrs indexes in patients with ventricular failure differ significantly from those in patients without failure. Pulmonary vascular congestion is regularly associated with an abnormal frequency dependence of resistance at low frequencies and with an increased resonant frequency. Discriminant analysis of Zrs indexes allows 92% correct classification of pulmonary capillary wedge pressures lower than and those equal to or higher than 18 mm Hg. Zrs differences between patients with and without left ventricular failure are consistent with the presence of a small airways obstruction even in patients with mild left ventricular failure. Furthermore, use of Zrs indexes permits moderate and severe pulmonary vascular congestion to be distinguished from one another and this is probably due to a significant narrowing of the large airways during severe left ventricular failure.

Role of circulating granulocytes in sheep lung injury produced by phorbol myristate acetate.

Phorbol myristate acetate (PMA) and endotoxin cause pulmonary granulocyte sequestration and alteration in lung fluid and solute exchange in awake sheep that are felt to be analogous to the adult respiratory distress syndrome in humans. The basic hypothesis that PMA causes lung injury by activating circulating granulocytes has never been tested. The effects of infused PMA on lung mechanics and the cellular constituents of lung lymph have also not been reported. We therefore characterized the effects of intravenous PMA, 5 micrograms/kg, on lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, blood and lymph leukocyte counts, and plasma and lymph cyclooxygenase products of arachidonate metabolism in 10 awake sheep with normal granulocyte counts and after granulocyte depletion with hydroxyurea. PMA significantly altered lung mechanics from base line in both nongranulocyte depleted and granulocyte-depleted sheep. Dynamic compliance decreased by over 50% and resistance to airflow across the lungs increased over threefold acutely following PMA infusion in both sets of experiments. Changes in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, and plasma and lymph arachidonate metabolites were not significantly affected by greater than 99% depletion of circulating granulocytes. We conclude that the lung injury caused by PMA in chronically instrumented awake sheep probably is not a result of activation of circulating granulocytes.

Respiratory pressure sensation. Relationship to changes in breathing pattern and PCO2 during acute increase in airway resistance in patients with chronic obstructive pulmonary disease.

The intensity of sensations experienced during breathing by patients with chronic obstructive pulmonary disease (COPD) might influence their ventilatory response to altered lung mechanics. In 8 patients with COPD (mean FEV1, 1.6 +/- 0.6 L SD) the acuity with which changes in intrathoracic pressure were perceived was studied by a standard psychophysical technique, magnitude production of inspiratory pressure. Subjects voluntarily produced mouth pressures proportional to numbers randomly presented, and the sensory acuity to changes in pressure was assessed from the slope of log-log plots of numbers versus pressures. These slopes were then related to the ventilatory responses of the patients to external resistive loads of 10 cm H2O/L/s, applied during both inspiration and expiration, and methacholine-induced bronchoconstriction, which doubled baseline specific airway resistance. Both modes of increase in airway resistance caused an increase in end-tidal PCO2 in all patients (range, 0.5 to 11 mmHg). The magnitude of CO2 retention correlated significantly with the change in tidal volume during both external loading and bronchoconstriction (r = -0.77, p less than 0.01); decreases in tidal volume were associated with increases in PCO2. The slope for magnitude production of pressure was inversely related to changes in tidal volume during both modes of increases in airway resistance (r = 0.61, p less than 0.01 for both bronchoconstriction and external resistive loads). Patients with the highest exponents for pressure changes (highest slopes) demonstrated the greatest decreases in tidal volume. Consequently, a direct relationship was found between the magnitude of the exponent and the magnitude of CO2 retention during loaded breathing and bronchoconstriction (r = 0.81, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Lung Mechanics in Pulmonary Edema

Pulmonary edema can cause alterations in lung mechanics that directly contribute to clinical morbidity and mortality rates. Both the location of the edema fluid (interstitital versus alveolar pulmonary edema) and the etiology of the pulmonary edema contribute to the severity and type of abnormalities of lung mechanics observed. The alterations in lung mechanics associated with the adult respiratory distress syndrome may involve the direct effects of released mediators, alterations in pulmonary surfactant, and altered airway reactivity, as well as the direct effects of the edema fluid.

1825 THE ROLE OF GRANULOCYTES IN THE LUNG FUNCTION RESPONSE TO GROUP B STREPTOCOCCAL TOXIN IN YOUNG LAMBS

Neonatal group B streptococcal sepsis is characterized by cardio-pulmonary failure, leukopenia and pulmonary leukostasis. The aim of this study was to evaluate the role of granulocytes (G) in the response to infusion of group B Type III streptococcal exotoxin. Five lambs, age 1-4 weeks, were studied awake in a whole-body, pressure-compensated, integrated-flow plethysmograph before and after neutrophil depletion with hydroxyurea. A two phase reaction to the toxin was observed. During the first phase, which lasted about 30 minutes, circulating G decreased, pulmonary arterial (PA) pressure, temperature and lung lymph flow increased. At the same time a 50% reduction in dynamic lung compliance (Cdyn) and a 300% increase in lung resistance (R1) was observed. Thoracic gas volume (TGV) was unchanged. In the second phase 3-5 h. after toxin, PA pressure and temperature remained slightly elevated, circulating G increased and lung lymph protein clearance (LPC) was doubled. In this phase R1, was moderately increased, but Cdyn and TGV were unaffected. After G depletion, GBS toxin infusion resulted in a significantly reduced increase in R1 (60%) in both phases and significantly less decrease in Cdyn (10%) in Phase I. PA pressure response was unchanged, whereas the increase in LPC was less marked. The results indicate that G contribute to, but are not the sole mediators, of altered lung mechanics and increased permeability of pulmonary exchange vessels seen after GBS toxin administration; whereas pulmonary hypertension does not appear to be mediated by G.

Effects of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia.

The effect of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia was studied in eight unanesthetized sheep. Platelets were depleted with rabbit anti-sheep platelet antibodies (APA). Bolus injections of APA alone caused marked pulmonary hypertension (PPA increased from 21 +/- 2 to 62 +/- 5 cm H2O +/- SE) and alterations in lung mechanics (dynamic compliance of the lung [Cdyn] decreased to 38.5 +/- 4.6% and resistance to air flow across the lung [RL] increased to 705 +/- 162% +/- SE of control), which were attenuated by pretreatment with meclofenamate. It was possible to deplete platelets before endotoxemia through a slow continuous infusion of APA without altering base-line values of the measured variables. Platelet depletion did not significantly attenuate the alterations in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, or the normal increase in lung lymph concentrations of thromboxane B2 or 6-keto-PGF1 alpha observed following endotoxemia in the sheep. We conclude that normal circulating platelet counts are not required for the full expression of the sheep's response to endotoxemia.

Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function.

Oxygen free radicals released during endotoxemia may contribute to the lung injury of the adult respiratory distress syndrome (ARDS). As this syndrome occurs frequently after gram-negative sepsis in humans, we studied the effect of intravenous N-acetylcysteine (NAC), a free radical scavenger, upon the endotoxin (E)-induced model of ARDS in awake sheep. In vivo studies demonstrated that NAC attenuates the endotoxin-induced rise in pulmonary artery pressure (62 +/- 3 torr with E control vs. 43 +/- 3 torr for E + NAC), and markedly diminishes the rise in lymph flow at 1 h (8.5 +/- 1.2 vs 4.5 +/- 0.6 ml/15 min) and 4 h (5.0 +/- 0.6 vs. 3.3 +/- 0.4 ml/15 min), respectively, for E control vs. E + NAC. NAC also markedly attenuated the alterations in lung mechanics after endotoxemia. Dynamic compliance at 2 h after endotoxemia was 44 +/- 6% of base line for E vs. 76 +/- 10% of base line for E + NAC. Resistance to airflow across the lung at 1 h postendotoxin was 811 +/- 280% of base line for E vs. 391 +/- 233% of base line for E + NAC. NAC substantially reduced the 1 h postendotoxin rise in lymph concentrations of thromboxane B2 (8.29 +/- 3.28 vs. 2.75 +/- 1.93 ng/ml for E vs. E + NAC) and 6-keto-prostaglandin-F1 alpha (0.91 +/- 0.27 vs. 0.23 +/- 0.12 ng/ml for E vs. E + NAC). In addition, in vitro studies were performed which revealed NAC to be a potent free radical scavenger in both biologic and nonbiologic free radical generating systems. NAC decreased phorbol-stimulated granulocyte aggregation in a concentration-dependent manner in vitro. Minimal effects were observed, however, upon leukocyte degranulation at the concentrations of NAC achieved during the in vivo tests. Thus, NAC significantly attenuated all monitored pathophysiologic changes in the endotoxin model of ARDS in sheep, possibly by its ability to scavenge toxic oxygen free radicals. A direct impairment of the ability of inflammatory cells to generate oxygen radicals cannot be ruled out.

Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep.

The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible role for cyclooxygenase products of arachidonate metabolism as mediators of the endotoxin-induced alterations in lung mechanics was investigated by studying sheep before and after cyclooxygenase inhibition with sodium meclofenamate and ibuprofen. Sheep were studied three times in random order: (a) sodium meclofenamate (or ibuprofen) infusion alone; (b) E. coli endotoxin alone; and (c) meclofenamate (or ibuprofen) and endotoxin. Meclofenamate alone had no effect on any of the variables measured. Endotoxin alone caused early marked changes in lung mechanics: resistance to airflow across the lungs (RL) increased 10-fold, dynamic lung compliance (Cdyn) decreased 80% and functional residual capacity (FRC) decreased by greater than 30%. The alveolar-to-arterial oxygen difference (delta AaPO2) increased markedly following endotoxemia. In the presence of sufficient meclofenamate to inhibit accumulation of thromboxane-B2 and 6-keto-prostaglandin F1 alpha in lung lymph, endotoxin caused no increase in RL, Cdyn decreased by less than 40%, and FRC decreased by only 6%. Meclofenamate significantly attenuated the hypoxemia and early pulmonary hypertension caused by endotoxemia but had no effect on the late increases in lung fluid and solute exchange. Ibuprofen had similar effects to those observed with meclofenamate. We conclude that both the pulmonary hypertension and changes in lung mechanics observed after endotoxemia may be mediated, at least in part, by constrictor prostaglandins or thromboxanes and that gas exchange may be improved by preventing endogenous synthesis of these mediators.

Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep.

To examine the role of circulating granulocytes in the airway changes caused by endotoxemia, we measured the response of chronically instrumented unanesthetized sheep to endotoxemia before and after granulocyte depletion with hydroxyurea. Granulocyte depletion did not affect the increases in mean pulmonary arterial pressure caused by endotoxin [peak pressure 59 +/- 8 cmH2O +/- (SE) control, 51 +/- 8 cmH2O granulocyte depleted]. However, the early (30-60 min after endotoxin) airway response to endotoxemia was markedly attenuated. Without granulocyte depletion, endotoxin caused dynamic compliance (Cdyn) to decrease to 41 +/- 10% of the base-line value and total lung resistance (RL) to increase to 283 +/- 61% of base line. When animals were granulocyte depleted, endotoxin decreased Cdyn to 69 +/- 6% (P less than 0.05) of base line and increased RL to 141 +/- 20% of base line (P less than 0.05). Granulocyte depletion also attenuated the effect of endotoxin on arterial oxygenation. During the maximum airway response to endotoxin, the alveolar-to-arterial oxygen gradient was 47 +/- 5 Torr in control studies and 32 +/- 2 Torr in granulocyte depleted studies (P less than 0.05). We conclude that interaction of granulocytes with the lung contributes to the changes in lung mechanics observed following endotoxemia and that the early pulmonary hypertension and the early alterations in lung mechanics caused by endotoxemia are caused by separate processes.

Effect of Simple Anthracite Pneumoconiosis on Lung Mechanics

A respiratory questionnaire was administered to 20 miners with simple anthracite coal workers' pneumoconiosis (CWP) and ten normal subjects. Lung function studies which included lung mechanics and small airways disease measurements were also performed. Seventeen of the miners admitted to having symptoms of bronchitis. No significant differences were demonstrated between the two groups for vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and three seconds (FEV3), midmaximal flow rate (FEF25-75%), and peak flow rate (PEFR). A significant decrease in the maximum expiratory flow rate at 50 percent of vital capacity (V max50%) was detected; however, this was not evident when the flow rate was corrected for lung volume. Also, there were no significant differences in lung volumes, diffusing capacity (DCO) and diffusion coefficient (DCO/TLC). The mean static expired compliance (Cstate) was significantly increased in the anthracite miners, but no difference in specific compliance (Cstate/FRC) could be demonstrated. Also, no significant differences were detected in the mean values of any of the tests of small airways disease. There is little evidence of significant alterations in lung mechanics or small airway narrowing in miners with simple anthracite pneumoconiosis.

Altered lung mechanics in neonates with persistent fetal circulation syndrome.

Altered lung mechanics in neonates with persistent fetal circulation syndrome.

Lung function in children with recurrent bronchitis.

Lung function was studied in 29 children suffering from recurrent bronchitis (average number of bronchitis attacks per year: 4.2 +/- 0.5). Most of them (73%) were 1--7 years old. The date of exploration in relation to the last acute bronchitis was on average 6 weeks. Lung mechanics, residual functional capacity, blood gases and regional lung function were measured. Most of the children were suffering from some kind of functional disorder; alteration of lung mechanics -- increase of lung resistance (22/29) decrease of dynamic compliance (15/23); increase of functional residual capacity (6/10), non specific bronchial hypersensitivity (12/17); regional ventilatory and perfusion malfunction. These functional disorders could be the first evidence of the bronchial lesions which cause chronic obstructive bronchitis in adults.

Relationship of anginal symptoms to lung mechanics during myocardial ischemia.

The anginal syndrome (AP) typically includes sensations of chest tightness or difficulty in breathing. Left ventricular (LV) dysfunction during myocardial ischemia incident with AP is now well documented. Since secondary alterations in lung mechanics could relate to these symptoms, we examined airway resistance (Raw), lung volume (TGV), lung compliance (C L ), and LV pressure-volume relations during pacing-induced AP. LV end-diastolic pressure (EDP) increased suddenly with AP, (mean + 41%, p < 0.01), without change in end-diastolic volume (EDV). LV distensibility (EDV/EDP) decreased abruptly, (–37%, P < 0.01), with reduction in airway conductance (1/Raw/TGV), (–40%, P < 0.05), and C L (–27%, P < 0.05). When AP was relieved, these changes returned toward preangina levels. Ischemia-induced LV dysfunction abruptly increases LVEDP. The resulting increased pulmonary capillary pressure effects an alteration of lung mechanics consisting of increasing Raw and reduced C L . The changes in ventilatory effort which ensue may be interpreted as chest tightness, heaviness, or constriction by the AP patient.