Changes In Respiratory System Mechanics Research Articles

Cardiorespiratory effects of different intraabdominal pressures in sheep: An experimental study.

Increased intraabdominal pressure (IAP) during laparoscopy can reduce venous return, but changes in respiratory system mechanics and their effect in left cardiac function are not well documented. This study evaluated the effects of different IAPs on respiratory mechanics and cardiac function in 10 healthy nonpregnant adult Santa Ines ewes randomly submitted to a crossover study using different IAPs: 0 mm Hg (G1), 10 mm Hg (G2), 12 mmHg (G3), and 15 mmHg (G4). Animals were anesthetized and mechanically ventilated (VT =15 ml/kg; positive end-expiratory pressure=3 cmH2 O; FiO2 =1.0). Pneumoperitoneum was induced by Hasson's trocar cannula. Variables were measured at INITIAL (IAP, 0 mmHg) and FINAL time points for each IAP after 1 h. At FINAL, driving airway pressure (ΔP,RS ), and percentage fraction of dead space (Vd/Vt) were higher in G3 and G4 than G1 (p=0.002, difference in means [MD] 4.60, 95% CI: 7.91-1.28, and p < 0.001, MD 5.4, 95% CI: 8.7-2.0; p=0.016, MD -9.5, 95% CI: -17.9 to -1.2; and p=0.027, MD -8.7, 95% CI: -17.1 to -0.4). The ejection fraction and fractional shortening were lower in G3 (p=0.039, MD -11.38, 95% CI: -0.07--22.68; p=0.015, MD -13.05, 95% CI: -1.74--24.36) and G4 (p=0.039, MD -9.94, 95% CI: -0.07 to -19.80; p=0.015, MD -11.43, 95%CI: -1.57 to -21.30, respectively) than G2. In G3, the maximum pulmonary flow velocity correlated negatively with ΔP,RS (r=-0.740; p=0.018), and Vd/Vt correlated positively with ΔP,RS (r=0.738, p=0.046). At IAP of 12 and 15 mm Hg impaired respiratory system mechanics, reduced left cardiac function and no change in maximum pulmonary artery flow velocity were detected. Therefore, respiratory mechanics should be monitored as an interplay to reduce left cardiac function.

Low‐dose administration of bleomycin leads to early alterations in lung mechanics

What is the central question of this study? When do alterations in pulmonary mechanics occur following chronic low-dose administration of bleomycin? What is the main finding and its importance? Remarkably, we report changes in lung mechanics as early as day7 that corresponded to parameters determined from single-frequency forced oscillation manoeuvres and pressure-volume loops. These changes preceded substantial histological changes or changes in gene expression levels. These findings are significant to refine drug discovery in idiopathic pulmonary fibrosis, where preclinical studies using lung function parameters would enhance the translational potential of drug candidates where lung function readouts are routinely performed in the clinic. Idiopathic pulmonary fibrosis (IPF) is the most widespread form of interstitial lung disease and, currently, there are only limited treatment options available. In preclinical animal models of lung fibrosis, the effectiveness of experimental therapeutics is often deemed successful via reductions in collagen deposition and expression of profibrotic genes in the lung. However, in clinical studies, improvements in lung function are primarily used to gauge the success of therapeutics directed towards IPF. Therefore, we examined whether changes in respiratory system mechanics in the early stages of an experimental model of lung fibrosis can be used to refine drug discovery approaches for IPF. C57BL/6J mice were administered bleomycin (BLM) or a vehicle control i.p. twice a week for 4weeks. At 7, 14, 21, 28 and 33days into the BLM treatment regimen, indices of respiratory system mechanics and pressure-volume relationships were measured. Concomitant with these measurements, histological and gene analyses relevant to lung fibrosis were performed. Alterations in respiratory system mechanics and pressure-volume relationships were observed as early as 7days after the start of BLM administration. Changes in respiratory system mechanics preceded the appearance of histological and molecular indices of lung fibrosis. Administration of BLM leads to early changes in respiratory system mechanics that coincide with the appearance of representative histological and molecular indices of lung fibrosis. Consequently, these data suggest that dampening the early changes in respiratory system mechanics might be used to assess the effectiveness of experimental therapeutics in preclinical animal models of lung fibrosis.

Aging-related changes in respiratory system mechanics and morphometry in mice.

Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice.

Sites of allergic airway smooth muscle remodeling and hyperresponsiveness are not associated in the rat

The cause-and-effect relationship between airway smooth muscle (ASM) remodeling and airway hyperresponsiveness (AHR) following allergen challenge is not well established. Using a rat model of allergen-induced ASM remodeling we explored the relationship between the site of ASM remodeling and AHR. Brown Norway rats, sensitized and challenged (3 times at 5-day intervals) with ovalbumin, were intranasally administered 0.1 mg/kg budesonide 24 and 1 h before challenge. Airway responses to aerosolized methacholine were assessed 48 h or 1 wk after three challenges. Airways were stained and analyzed for total airway wall area, area of smooth muscle-specific α-actin, and goblet cell hyperplasia, and the constant-phase model was used to resolve the changes in respiratory system mechanics into large airway and peripheral lung responses. After three ovalbumin challenges, there was a significant increase in ASM area and in the total wall area in all sized airways as well as an increase in goblet cells in the central airways. Budesonide inhibited ASM growth and central airway goblet cell hyperplasia following ovalbumin challenges. Budesonide also inhibited small but not large airway total wall area. AHR was attributable to excessive responses of the small airways, whereas responsiveness of the large airways was unchanged. Budesonide did not inhibit AHR after repeated challenge. We conclude that ASM remodeling induced by repeated allergen challenges involves the entire bronchial tree, whereas AHR reflects alterations in the lung periphery. Prevention of ASM remodeling by corticosteroid does not abrogate AHR.

Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation

Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min(-1), tidal volume 10 ml x kg(-1), positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin-6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-alpha was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.

A novel adaptive control system for noisy pressure-controlled ventilation: a numerical simulation and bench test study

There is growing interest in the use of both variable and pressure-controlled ventilation (PCV). The combination of these approaches as "noisy PCV" requires adaptation of the mechanical ventilator to the respiratory system mechanics. Thus, we developed and evaluated a new control system based on the least-mean-squares adaptive approach, which automatically and continuously adjusts the driving pressure during PCV to achieve the desired variability pattern of tidal volume (V (T)). The controller was tested during numerical simulations and with a physical model reproducing the mechanical properties of the respiratory system. We applied step changes in respiratory system mechanics and mechanical ventilation settings. The time needed to converge to the desired V (T) variability pattern after each change (t (c)) and the difference in minute ventilation between the measured and target pattern of V (T) (DeltaMV) were determined. During numerical simulations, the control system for noisy PCV achieved the desired variable V (T) pattern in less than 30 respiratory cycles, with limited influence of the dynamic elastance (E*) on t (c), except when E* was underestimated by >25%. We also found that, during tests in the physical model, the control system converged in <60 respiratory cycles and was not influenced by airways resistance. In all measurements, the absolute value of DeltaMV was <25%. The new control system for noisy PCV can prove useful for controlled mechanical ventilation in the intensive care unit.

Moderate hypothermia attenuates changes in respiratory system mechanics and cytokine production during low lung volume ventilation in rats

Hypothermia was shown to attenuate ventilator-induced lung injury (VILI) in high end-inspiratory lung volume models of VILI [1-3]. Experimental evidence suggests that moderate tidal volumes may, under certain clinical conditions that induce alveolar instability, lead to a lung injury [4]. Recent studies have also suggested that insults like shock [5] or surgery [6] sensitize the lung to injury by priming for an exaggerated response to a second stimulus. The aim of this study was to investigate whether moderate hypothermia attenuates low lung volume injury during low PEEP, high FiO2 and moderate tidal volume ventilation in animals sensitized to injury by previous anesthesia and surgery.

Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome

AIMTo investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.METHODSStarting within 24 hours of age, ventilated preterm...

The Effect of Oral Clonidine Premedication on Changes in Respiratory System Mechanics by Tracheal Intubation

The Effect of Oral Clonidine Premedication on Changes in Respiratory System Mechanics by Tracheal Intubation

Strength of the Breuer-Hering inflation reflex in term and preterm infants.

The effect of the presence of the respiratory distress syndrome (RDS) or related factors (static compliance of the respiratory system and transcutaneous blood gases) and gestational age on the strength of the Breuer-Hering inflation reflex (BHIR) was studied in three groups of infants. Twenty-six ventilated preterm infants with and without RDS were studied 6 h after birth (group 1). In 24 preterm infants, we followed the development of reflex strength during the first year of life (group 2). Twenty-one healthy nonintubated term infants were studied within the first week of life (group 3). The BHIR was initiated by end-inspiratory occlusions, and the strength was characterized by the ratio of expiratory time after and without preceding airway occlusion. The static compliance of the respiratory system in ventilated infants was assessed by the multiple-occlusion technique. In group 1, reflex strength declined with increasing gestational age; in the presence of RDS or low respiratory compliance, the decline was less. Transcutaneous blood gases did not affect reflex strength. At term age, reflex strength was similar in spontaneously breathing preterm (group 2) and term infants (group 3). The BHIR decreased in strength during the first year after preterm birth. We conclude that 1) the strength of the BHIR decreases with increasing gestational and postnatal ages and 2) RDS, due to changes in respiratory system mechanics, causes an increase in reflex strength.

Mechanical respiratory system input impedance during high-frequency oscillatory ventilation in rabbits

To study the mechanical properties of the rabbit respiratory system during high-frequency oscillatory ventilation by means of mechanical respiratory impedance measurement and to characterize the changes in oscillation mechanics of the respiratory system occurring after bilateral vagotomy. Acute experimental trial. Physiology laboratory. Ten adult rabbits (mean body weight 3.1 kg). Anesthetized rabbits were exposed to short runs of high-frequency oscillatory ventilation, with stroke volumes of 5.0, 6.6, and 10.0 mL, applied at oscillation frequencies of 10, 15, 20, and 25 Hz before and after vagotomy. Mechanical respiratory input impedance was determined from the pressure and flow signals simultaneously measured at the airway opening and analyzed in terms of its real and imaginary parts. (The real part of respiratory impedance characterizes the resistive property of the lungs and chest wall; the imaginary part of respiratory impedance characterizes the elastic and inertial properties of the lungs and chest wall.) At all stroke volumes and oscillation frequencies studied, vagotomy resulted in a decrease in the real part of respiratory impedance. After vagotomy, the real part of respiratory impedance was stroke volume-independent, and exhibited negative frequency dependency. Vagotomy also led to a decrease in the imaginary part of respiratory impedance, mainly at lower oscillation frequencies, and thus, to a higher resonant frequency of the respiratory system. Mechanical respiratory impedance measurement proved to be a useful method to study the mechanical properties of the respiratory system during high-frequency oscillatory ventilation. The results suggest that vagally mediated reflex changes in respiratory system mechanics are associated with high-frequency oscillatory ventilation, depending on the ventilatory variables that are used.

Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression.

The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of continuous positive airway pressure on upper airway and respiratory muscle activity.

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.