Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects

We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of substance P on cardiovascular and respiratory function in subjects

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.     

Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects

The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.     

Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth

Five dogs underwent left pneumonectomy at 10 wk of age, whereas four littermates underwent a sham operation. At 26 wk of age the postpneumonectomy dogs had total lung vital capacity (VC) and lung weight similar to controls, but maximum expiratory flow was reduced. Pressure capsules were glued to right lower (RLL) and right cardiac (RCL) lobes, and alveolar pressures (PA) were measured during forced expiration. In postpneumonectomy dogs RLL and RCL both emptied more slowly than in control dogs, and emptying was especially delayed in RCL, which underwent the most growth. When both lobes deflated together, PA in RCL and RLL were similar in control dogs, but in postpneumonectomy dogs PA in RCL exceeded that in RLL by approximately 3 cmH2O from 80 to 20% VC. Because the higher driving pressure in RCL compensated for the relatively high resistance of RCL, the pattern of lobar emptying was relatively uniform over these lung volumes. This result was compatible with interdependence of lobar maximum expiratory flows. In addition, at PA of 6-10 cmH2O in postpneumonectomy dogs, maximum emptying rates of RCL were less when RCL deflated alone than when RCL and RLL emptied together, again demonstrating interdependence of lobar maximum expiratory flow.     

Interaction of inhaled LTC4 with histamine and PGD2 on airway caliber in asthma

To investigate possible mediator interaction in asthma, the effect of inhaled leukotriene (LT) C4 on bronchoconstriction provoked by histamine and prostaglandin (PG) D2 was studied in nine asthmatic subjects. The provocation doses of histamine, PGD2, and LTC4 required to produce a 12.5% decrease in baseline forced expiratory volume in 1 s (FEV1, PD12.5) and to further this fall to 25% (PD25-12.5) were determined. On three subsequent occasions, subjects inhaled either the PD12.5 LTC4 plus vehicle or vehicle plus the PD25-12.5 of either histamine or PGD2, and FEV1 and maximal flow at 70% of vital capacity below total lung capacity after a forced partial expiratory maneuver (Vp30) followed for 45 min. From these results, predicted time-course curves for LTC4 with histamine and LTC4 with PGD2 were calculated. On two final occasions, airway caliber was followed for 45 min after inhalation of the PD12.5 LTC4 followed by the PD25-12.5 of either histamine or PGD2. During the first 9 min after LTC4-histamine and LTC4-PGD2, the decreases in airway caliber were greater than the calculated predicted response. This interaction, although small, was significant with LTC4-PGD2 for both FEV1 (P = 0.01) and Vp30 (P less than 0.05) and with LTC4-histamine for Vp30 (P less than 0.05) but not for FEV1 (P less than 0.05). We conclude that inhaled LTC4 interacts synergistically with histamine and PGD2 and that this effect, although small, may be a relevant interaction in asthma.     

Bronchoalveolar lavage fluid obtained from smokers exhibits increased monocyte chemokinetic activity

Alveolar macrophages, which are cells derived from blood monocytes, accumulate within the lower respiratory tract of cigarette smokers. One mechanism to account for this accumulation of alveolar macrophages may be an increase in the migration of blood monocytes into the lungs of smokers. To evaluate this hypothesis, bronchoalveolar lavage fluid (BALF) was obtained from 15 smokers and 16 nonsmokers. The smokers' BALF possessed a significantly increased capacity to attract normal blood monocytes when evaluated using a blind-well chamber technique (26.2 +/- 7.6 vs 14.8 +/- 6.9 cells/high-power field, P less than 0.01). Checkerboard analysis of the activity revealed that it was predominantly chemokinetic. Partial characterization of the activity in smokers' BALF revealed that it was lipid soluble but only partially sensitive to trypsin and heat. The chemokinetic activity correlated with alveolar macrophage numbers in the BALF (r = 0.4391, P = 0.009). Furthermore, both the chemokinetic activity and alveolar macrophage number correlated with alterations of respiratory function (forced expiratory volume in 1 s, diffusing capacity for carbon monoxide, and forced expiratory flow at 75% of the vital capacity). These results suggest that the increase in alveolar macrophage number present in the BALF of cigarette smokers may be due, at least in part, to an increased amount of chemokinetic factor(s) in the smokers' BALF, and these factor(s) may participate in the decline of respiratory function associated with cigarette smoking, probably by recruiting monocytes into lung.     

Relation of pressure and flow of pulmonary circulation in patients with chronic obstructive pulmonary disease

A series of 31 patients with various degrees of chronic obstructive pulmonary disease underwent right heart catheterization using flow-directed thermodilution catheters. Both rest and supine exercise values were obtained. The patients were divided into two groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 values of greater than or equal to 1,300 ml (group 1), the arterial oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 of less than or equal to 1,200 ml (group 2) PaO2 significantly (p less than 0.05) fell in response to exercise. In group 2, a significant increase of total pulmonary resistance (TPR) with exercise was found (p less than 0.01). Pulmonary vascular resistance (PVR) remained unchanged in both subgroups. It is suggested that the value of PVR for subgroup 2 is artificially low because an important variable, namely pulmonary artery wedge pressure, is influenced by alveolar pressure in patients with an uneven distribution of perfusion and ventilation at pulmonary venous pressures lower than alveolar pressure. The steeper slope of the pressure-flow relationship in these patients is probably due to an increased vascular tone caused by chronic hypoxia at rest and further fall of PaO2 and rise of arterial CO2 partial pressure in response to exercise.     

Reactive oxygen species in the killing of Pseudomonas aeruginosa by human leukocytes

Pseudomonas aeruginosa (PA) infects hosts with compromised host defenses. An important defense mechanism is the generation of reactive oxygen species (ROS) by white blood cells (WBCs). What roles do ROS play in host defense against PA? Human WBCs killed PA in vitro, and they generated a respiratory burst as measured by the production of H₂O₂. ROS efficiently killed PA; in acellular assays, less than 10mm of H₂O₂ or OCl^- eliminated all bacteria in 90 min. However, WBCs with suppressed production of ROS (caused by hypoxia) killed PA normally. In addition, none of the antioxidants vitamin C, N-acetylcysteine, superoxide dismutase, or catalase affected PA killing by WBCs. Thus, PA stimulates WBCs to produce ROS, which can kill the bacteria, but disturbances of WBC ROS production do not interfere with the killing of PA. WBCs have robust, redundant mechanisms for PA elimination.     

Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal human lung

Amodel integrating airway/lung mechanics, pulmonary blood flow, and gasexchange for a normal human subject executing the forced vital capacity(FVC) maneuver is presented. It requires as input the intrapleuralpressure measured during the maneuver. Selected model-generated outputvariables are compared against measured data (flow at the mouth, changein lung volume, and expired O₂ and CO₂concentrations at the mouth). A nonlinear parameter-estimation algorithm is employed to vary selected sensitive model parameters toobtain reasonable least squares fits to the data. This study indicatesthat 1) all three components of the respiratory model arenecessary to characterize the FVC maneuver; 2) changes in pulmonary blood flow rate are associated with changes in alveolar andintrapleural pressures and affect gas exchange and the time course ofexpired gas concentrations; and 3) a collapsible midairway segment must be included to match airflow during a forced expiration. Model simulations suggest that the resistances to airflow offered bythe collapsible segment and the small airways are significant throughout forced expiration; their combined effect is needed toadequately match the inspiratory and expiratory flow-volume loops.Despite the limitations of this lumped single-compartment model, aremarkable agreement with airflow and expired gas concentration measurements is obtained for normal subjects. Furthermore, the modelprovides insight into the important dynamic interactions betweenventilation and perfusion during the FVC maneuver.

     

Simulation of the effects of mechanical nonhomogeneities on expiratory flow from human lungs

A computational model for expiration from lungs with mechanical nonhomogeneities was used to investigate the effect of such nonhomogeneities on the distribution of expiratory flow and the development of alveolar pressure differences between regions. The nonhomogeneities used were a modest constriction of the peripheral airways and a 50% difference in compliance between regions. The model contains only two mechanically different regions but allows these to be as grossly distributed as left lung-right lung or to be distributed as a set of identical pairs of parallel nonhomogeneous regions with flows from each merging in a specified bronchial generation. The site of flow merging had no effect on the flow-volume curve but had a significant effect on the development of alveolar pressure differences (delta PA). With the peripheral constriction, greater values of delta PA developed when flows were merged peripherally rather than centrally. The opposite was true in the case of a compliance nonhomogeneity. The delta PA values were smaller at submaximal flows. Plots of delta PA vs. lung volume were similar to those obtained experimentally. These results were interpreted in terms of the expression used for the fluid mechanics of the merging flows. delta PA was greater when the viscosity of the expired gas was increased or when its density was reduced. Partial forced expirations were shown to indicate the presence of mechanical nonhomogeneity.     

Airway effects of purine nucleosides and nucleotides and release with bronchial provocation in asthma

Adenosine, AMP, and ADP all caused similar concentration-related bronchoconstriction when inhaled by patients with asthma, whereas the adenosine hydrolysis product inosine had no effect. Geometric mean provocation concentrations of adenosine AMP and ADP causing a 20% fall in forced expiratory volume in 1 s (PCf20) were 2.34, 4.27, and 2.19 mumol/ml and 40% fall in specific airway conductance (PCs40) 3.16, 5.01, and 2.0 mumol/ml. Bronchoconstriction was rapid in onset, reaching a maximum 2-5 min after a single inhalation of AMP. In 31 asthmatic subjects a positive correlation was established between airway responsiveness to histamine, as an index of non-specific responsiveness, and airway reactivity to adenosine (PCf20, r = 0.60; PCs40, r = 0.64; P less than 0.01). Following bronchial provocation with allergen in nine subjects, plasma levels of adenosine increased from a mean base line of 5.4 +/- 0.9 to 9.6 +/- 2.0 ng/ml at 15 min (P less than 0.01) in parallel with a fall in forced expiratory volume in 1 s. With methacholine provocation bronchoconstriction reached maximum 2-5 min postchallenge being followed by, but not accompanied by, significant increases in plasma levels of adenosine. These data suggest that adenosine is a specific bronchoconstrictor that may contribute to airflow obstruction in asthma.     

Right and left ventricular pressure-volume response to respiratory maneuvers

With respiration, right ventricular end-diastolic volume fluctuates. We examined the importance of these right ventricular volume changes on left ventricular function. In six mongrel dogs, right and left ventricular volumes and pressures and esophageal pressure were simultaneously measured during normal respiration, Valsalva maneuver, and Mueller maneuver. The right and left ventricular volumes were calculated from cineradiographic positions of endocardial radiopaque markers. Increases in right ventricular volume were associated with changes in the left ventricular (LV) pressure-volume relationship. With normal respiration, right ventricular end-diastolic volume increased 2.3 +/- 0.7 ml during inspiration, LV transmural diastolic pressure was unchanged, and LV diastolic volume decreased slightly. This effect was accentuated by the Mueller maneuver; right ventricular end-diastolic volume increased 10.4 +/- 2.3 ml (P less than 0.05), while left ventricular end-diastolic pressure increased 3.6 mmHg (P less than 0.05) without a significant change in left ventricular end-diastolic volume. Conversely, with a Valsalva maneuver, right ventricular volume decreased 6.5 +/- 1.2 ml (P less than 0.05), and left ventricular end-diastolic pressure decreased 2.2 +/- 0.5 mmHg (P less than 0.05) despite an unchanged left ventricular end-diastolic volume. These changes in the left ventricular pressure-volume relationship, secondary to changes in right ventricular volumes, are probably due to ventricular interdependence. Ventricular interdependence may also be an additional factor for the decrease in left ventricular stroke volume during inspiration.     

Effects of changes in left ventricular loading and pleural pressure on mitral flow

The cause of the fall in left ventricular (LV) stroke volume (SV) during a fall in pleural pressure (Pp1) has been in dispute for over a century. We have defined the changes in the temporal relationship between LV inflow (Qm) and outflow (Qa) in a canine preparation to test the mutually exclusive hypotheses that the fall in LVSV is caused only by changes during diastole (e.g., ventricular interdependence) or only by changes during systole (e.g., afterload). The ability of the experimental preparation to measure the results of acute changes in right heart volume or output and acute changes in LV afterload was validated in open-chest studies with and without pericardial constraint. In closed-chest studies, with a fall in Pp1 during a Mueller maneuver Qm reached both its inspiratory minimum and expiratory maximum before Qa in 80% of the Mueller maneuvers, invalidating both hypotheses, which each required that one flow lead the other in 100% of the Mueller maneuvers. Review of individual records suggested that if the rapid changes in Pp1 occurred during systole, Qa could vary in a manner independent of the preceding Qm. These studies suggest that both diastolic and systolic events may contribute to the fall in SV, while causing opposite changes in LV volumes.     

Laryngeal resistance immediately after panting in control and constricted airways

Laryngeal resistance (Rla) in the postpanting interval (PPRla) was examined in five normal subjects in the control state and with methacholine- and histamine-induced bronchoconstriction. Respiratory resistance (Rrs) was measured by the forced oscillation technique at 10 Hz, and Rla was measured by the low-frequency sound method (Sekizawa, K., C. Shindoh, W. Hida, S. Suzuki, et al. J. Appl. Physiol. 55:591-597, 1983). Inspiratory Rrs (IRrs) was lower than expiratory Rrs (ERrs), and Rrs immediately after panting (PPRrs) was not significantly different from IRrs in the three airway conditions. Rla increased with bronchoconstriction and inspiratory Rla (IRla) was lower than expiratory Rla (ERla). PPRla was lower than IRla (P less than 0.01) by an amount corresponding to the decrease in Rrs in the control airway. However, in constricted airways, PPRla was higher than IRla and about the same as ERla. We suggest that the panting maneuver is suitable for minimizing the effect of laryngeal artifact in the control airway, but in the constricted airway the panting maneuver may fail to cause widening of the laryngeal orifice.     

Infarct-induced chronic heart failure increases bidirectional protein movement across the alveolocapillary barrier

Chronic heart failure (CHF) is associated with adaptive structural changes at the alveolocapillary barrier that may be associated with altered protein permeability. Bidirectional protein movement across the barrier was studied in anesthetized rats with infarct-induced CHF by following (125)I-labeled albumin ((125)I-albumin) flux into the alveoli and the leakage of surfactant protein (SP)-B from the alveoli into the circulation. Three groups were studied: controls [0% left ventricular (LV) infarction], moderate infarct (25-45% LV infarction), and large infarct (>46% LV infarction). Wet and dry lung weights increased in the large infarct group (both P < 0.001), consistent with increased lung water and solid lung tissue. (125)I-albumin flux increased across the endothelial (P < 0.001) and epithelial (P < 0.01) components of the alveolocapillary barrier in the large infarct group. Plasma SP-B increased 23% with moderate infarcts (P < 0.05) and 97% with large infarcts (P < 0.001), independent of alveolar levels. Lavage fluid immune cells (P < 0.01) and myeloperoxidase activity (P < 0.05) increased in the large infarct group, consistent with inflammation. Bidirectional protein movement across the alveolocapillary barrier is increased in CHF, and alveolar inflammation may contribute to this pathophysiological defect.     

Transient analysis of cardiopulmonary interactions. II. Systolic events

The etiology of the fall in left ventricular stroke volume (LVSV) and arterial pressure with a negative intrathoracic pressure (NITP) during inspiration is controversial. An increase in LV afterload produced by NITP has been proposed as one explanation but is difficult to evaluate if preload is also altered. To test the hypothesis that a systolic event alone, i.e., a change in LV afterload or contractility, can reduce LVSV during inspiration independent of changes in LV preload, a rapid transient NITP confined to systole was produced by electrocardiogram-triggered phrenic nerve stimulation in eight anesthetized dogs. Intrathoracic descending aortic diameters were measured by sonomicrometry to transduce qualitative changes in aortic transmural pressure. With the airway completely obstructed systolic NITP resulted in a decrease in LVSV (-8.1%, P less than 0.001) but an increase in the systolic anteroposterior (0.54 mm, P less than 0.01) and right-to-left (0.45 mm, P less than 0.01) aortic diameters compared with preceding beat. Similar significant changes were observed with the airway unobstructed. These observations are consistent with an increased afterload imposed on the LV reducing LVSV and egress of blood out of the thorax. Prolonging NITP to include both systole and diastole, a profound fall in LVSV is observed, consistent with the independent influences of systolic and diastolic events combining to diminish LVSV.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Exercise response after rapid intravenous infusion of saline in healthy humans.

Patients with chronic heart failure have an abnormal pattern of exercise ventilation (Ve), characterized by small tidal volumes (Vt), increased alveolar ventilation, and elevated physiological dead space (Vd/Vt). To investigate whether increased lung water in isolation could reproduce this pattern of exercise ventilation, 30 ml/kg of saline were rapidly infused into nine normal subjects, immediately before a symptom-limited incremental exercise test. Saline infusion significantly reduced forced vital capacity, 1-s forced expiratory volume, and alveolar volume (P < 0.01 for all). After saline, exercise ventilation assessed by the Ve/Vco(2) slope increased from 24.9 +/- 2.4 to 28.0 +/- 2.9 l/l, (P < 0.0002), associated with a small decrease in arterial Pco(2), but without changes in Vt, Vd/Vt, or alveolar-arterial O(2) difference. A reduction in maximal O(2) uptake of 175 +/- 184 ml/min (P < 0.02) was observed in the postsaline infusion exercise studies, associated with a consistent reduction in maximal exercise heart rate (8.1 +/- 5.9 beats/min, P < 0.01), but without a change in the O(2) pulse. Therefore, infusion of saline to normal subjects before exercise failed to reproduce either the increase in Vd/Vt or the smaller exercise Vt described in heart failure patients. The observed increase in Ve can be attributed to dilution acidosis from infusion of the bicarbonate-free fluid and/or to afferent signals from lung and exercising muscles. The reduction in maximal power output, maximal O(2) uptake, and heart rate after saline infusion may be linked to accumulation of edema fluid in exercising muscle, impairing the diffusion of O(2) to muscle mitochondria.     

Reduction of eicosanoid production by essential fatty acid depletion does not attenuate the inflammatory response induced by Pseudomonas aeruginosa pneumonia in rat lung.

Sipid mediators of inflammation have been implicated in the pathogenesis of Pseudomonas aeruginosa (PA) related pulmonary damage in patients with cystic fibrosis. We studied the role of these mediators in a rat model of PA endobronchitis using essential fatty acid deficient (EFAD) animals. Whole blood from EFAD animals produced significantly less leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid when stimulated ex vivo than did whole blood from control animals (p less than 0.005). Similarly, lung lavage fluid from EFAD animals infected with PA contained less LTB4 and thromboxane B2 (TXB2) than that from control animals. Despite these differences, cellular infiltration of airways in response to PA infection was virtually identical in animals from the regular diet and the EFAD groups. Both EFAD and control animals had a significant increase in white blood cells (WBC) in lung lavage fluid at 1, 3 and 6 days following infection with PA when compared to animals receiving sterile beads. Localized areas of consolidation and nodularity were grossly evident in the lungs of all PA infected animals irrespective of their ability to generate the lipid inflammatory mediators. Microscopic examination of lung sections demonstrated similar changes in all infected animals. We conclude that LTB4 and TXB2 production occurs early in the course of PA pulmonary infection in rats. This early rise in lipid mediators is temporally associated with an influx of WBC into the airways. However, attenuation of eicosanoid production by use of an EFAD diet does not lead to a reduction in the inflammatory response to PA infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interdependence of regional expiratory flow

Flows from different lung regions interact at the junctions of the bronchial tree, and flow from each region depends on the driving pressures for other regions. At each junction, flow from the region with the higher driving pressure is favored. As a result there is a limit on the difference in alveolar pressures that can develop during expiratory flow from a lung with regional differences in lung compliance and airway resistance. The limiting pressure difference is smaller for lower flow. A nonuniform lung therefore empties more uniformly if it empties slowly, and maximum flow at low lung volume may be greater than it would be at the same lung volume during a maximal expiratory vital capacity maneuver.