A. Adamicza

Lung volumes and respiratory mechanics in elastase-induced emphysema in mice

Absolute lung volumes such as functional residual capacity, residual volume (RV), and total lung capacity (TLC) are used to characterize emphysema in patients, whereas in animal models of emphysema, the mechanical parameters are invariably obtained as a function of transrespiratory pressure (Prs). The aim of the present study was to establish a link between the mechanical parameters including tissue elastance (H) and airway resistance (Raw), and thoracic gas volume (TGV) in addition to Prs in a mouse model of emphysema. Using low-frequency forced oscillations during slow deep inflation, we tracked H and Raw as functions of TGV and Prs in normal mice and mice treated with porcine pancreatic elastase. The presence of emphysema was confirmed by morphometric analysis of histological slices. The treatment resulted in an increase in TGV by 51 and 44% and a decrease in H by 57 and 27%, respectively, at 0 and 20 cmH(2)O of Prs. The Raw did not differ between the groups at any value of Prs, but it was significantly higher in the treated mice at comparable TGV values. In further groups of mice, tracheal sounds were recorded during inflations from RV to TLC. All lung volumes but RV were significantly elevated in the treated mice, whereas the numbers and size distributions of inspiratory crackles were not different, suggesting that the airways were not affected by the elastase treatment. These findings emphasize the importance of absolute lung volumes and indicate that tissue destruction was not associated with airway dysfunction in this mouse model of emphysema.

Development of bronchoconstriction after administration of muscle relaxants in rabbits with normal or hyperreactive airways

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% ± 29% and 0.80 ± 0.12 cm H2O/L, respectively) and mivacurium (80% ± 25% and 0.71 ± 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% ± 12% and 0.41 ± 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity.

Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (eta = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol x kg(-1)) each evoked significant dose-related increases in Raw, G, H and eta. Pretreatment with 20 nmol x kg(-1) BQ-610 (a highly selective ETA receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol-kg(-1) BQ-610, with 20 nmol x kg(-1) ETR-P1/fl (a novel ETA receptor antagonist) or with 20 nmol x kg(-1) IRL 1038 (an ETB receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.

The involvement of histaminic and muscarinic receptors in the bronchoconstriction induced by myorelaxant administration in sensitized rabbits

BACKGROUND:Muscle relaxants cause bronchospasm via histamine release and/or by acting on the muscarinic receptors; we sought to characterize the respective importance of these pathways in the presence of bronchial hyperreactivity. METHODS:Ovalbumin-sensitized rabbits were randomly assigned to several protocol groups: Group C comprised untreated animals; in the other three groups, either H1 and H2 histaminic receptor blockade was performed, leaving the M1, M2, and M3 muscarinic receptors functional (Group M123), or combining this treatment with M3 muscarinic receptor blockade (Group M12), or with vagotomy (Group M3). Respiratory system impedance was measured over a 90-s period, during which succinylcholine, mivacurium or atracurium was administered. To monitor the changes in lung mechanics, respiratory system impedance was averaged in a 2-s time window and fitted by a model featuring airway resistance and inertance and tissue damping and elastance. RESULTS:The peak increases in airway resistance in Group C were greatest with succinylcholine (79 ± 17[SE]%) and mivacurium administration (75% ± 12%), whereas they were lower after attracurium (40% ± 11%). These changes were markedly attenuated by both histamine and muscarinic receptor blockade with the largest reduction in Group M3 for succinylcholine (14% ± 5.2%), and in Group M123 for mivacurium (5.1% ± 9.1%) and attracurium (7.8% ± 4.0%). DISCUSSION:Although the bronchospasm developing in the allergic airways after muscle relaxants is mediated primarily by the histaminic pathway, the interactions of succinylcholine on the M1, M2, and M3 receptors, those of atracurium on the M1 and M2 receptors, and those of mivacurium on the M3 receptors may also play a role.

Pulmonary mechanical responses to intestinal ischaemia-reperfusion and endotoxin preconditioning.

During intestinal ischaemia-reperfusion, endotoxin can be translocated. Pretreatment with sublethal doses of endotoxin develops tolerance to ischaemia-reperfusion in different organs; however, the tolerance to intestinal ischaemia-reperfusion in the lung has rarely been investigated. Our aim was to study the role of endotoxin pretreatment in the mechanical responses and inflammatory activation induced by intestinal ischaemia-reperfusion in the lung. Wistar rats were preconditioned with a sublethal dose of endotoxin on day -3 or -1. On day 0, anesthetized, paralyzed and mechanically ventilated rats were subjected to a 60-min occlusion of the superior mesenteric artery and a subsequent 240-min reperfusion. The low-frequency forced oscillation technique was employed to characterize the separate mechanical responses of the airways and respiratory tissues. Intestinal ischaemia-reperfusion caused a significant decrease in airway resistance and increases in tissue resistance and elastance, nitric oxide synthase and myeloperoxidase activities. Pretreatment with endotoxin modified both the pulmonary mechanical responses and the inflammatory markers in the lung during intestinal ischaemia-reperfusion. We conclude that endotoxin or the endotoxin-induced processes (and humoral mediators) have significant roles in the pathomechanism of the remote pulmonary effect of intestinal ischaemia-reperfusion.

Effect of pulmonary edema on changes in lung mechanics in rats

Because of similar pathophysiologic changes, oleic acid (OA)-induced pulmonary edema has been well established as an experimental model of certain types of ARDS. Data in the literature indicate changes mostly in global pulmonary mechanical parameters (lung resistance and compliance) during permeability-type edema. Therefore, we designed this study (1) to separate the OA-induced mechanical responses into airway and parenchymal components, and (2) to examine the relationship between the mechanical parameters and the degree of edema. Anaesthetized, paralyzed, mechanically ventilated rats were given iv. OA in doses of 0 (C n=9), 0.05 (OA0.05 n=8), 0.1 (OA0.1 n=10) and 0.3 (OA0.3 n=5) ml/kg. Respiratory system impedance was measured with a wave-tube low-frequency forced oscillation technique, and a model fitting was used to estimate airway (Raw) and lung tissue parameters (G, parenchymal damping; H, elastance). Pulmonary edema was quantified by gravimetric analysis (WW/DW, wet-to-dry weight ratio). In the OAL0.05 group, transient, but significant increase in Raw, only slight increase in H, and no response in G was observed. Different responses were obtained in OA0.1: significant Raw, G, and H values in survivors; rapid and significantly higher responses in all three parameters in non-survivors. Extremely large parameter values were measured in OA0.3. We found that OA caused dose-related increases in WW, DW and WW/DW. Highly significant correlations were found between the degree of edema and G or H, but not Raw. This study demonstrates that low dose of OA had only transient lung mechanical effects; however, it resulted in mild edema. The higher dose elicited significant airway and tissue changes (smaller responses in survivors than in non-survivors), and severe edema. The strong correlation between lung tissue parameters and the degree of edema suggests that the OA-induced acute lung injury is manifested primarily in the alterations in parenchymal mechanics.