Changes In Dynamic Lung Compliance Research Articles

The Stepwise Slow Titration of Positive End-Expiratory Pressure Before the End of General Anaesthesia Improves Lung Mechanics in Children: A Randomized Open Label Clinical Trial

Background: Intraoperative application of positive end-end-expiratory pressure (PEEP) is recommended in mechanically ventilated children since it improves lung mechanics. However, inadequate level of applied pressure can increase risk of barotrauma. Objectives: To assess the impact of titrated PEEP on lung mechanics in mechanically ventilated children under general anaesthesia. Methods: This was an open label, single Tertiary Centre randomized controlled clinical trial. The study population included 70 preschool children, ASA I and II, scheduled for orthopaedic, reconstructive, abdominal or urological surgery. Children with upper respiratory tract infection, allergic to chosen anaesthetics, cardiorespiratory comorbidities were excluded. Patients were randomly assigned either to receive intraoperative PEEP titration form 5 - 11 cmH2O 20 minutes before the end of anaesthesia (intervention group) or to be ventilated until the end of anaesthesia conventionally with a positive end-expiratory pressure of 3 cmH2O (control group). Main outcomes: changes in dynamic lung compliance (Cdyn), peak airway pressure (PIP), mean airway pressure (Paw) between groups at the end of surgery; changes in PIP and Paw during PEEP titration and desaturation in interventional group during PEEP titration. Results: Seventy preschool children were recruited and analysed. Intraoperative positive end-expiratory pressure titration improved Cdyn in the intervention group comparing to control (ΔCdy -3.2 vs. 0.63; P < 0.001). PIP and Paw were higher in interventional group (ΔPIP -0.57vs. 0.11; P < 0.001, and ΔPaw -0.63 vs. 0.0; P < 0.001) and desaturation was not observed in interventional group. Conclusions: Stepwise titration of PEEP up to 11 cmH2O improves subsequent lung mechanics without causing of barotrauma.

Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats1

To determine the effects of acetamide-45 on respiratory function, airway inflammation, and the activity of phosphodiesterase 4 (PDE4) in allergic rats. Rats were sensitized by a single intramuscular injection with ovalbumin (OVA) and were challenged with ovalbumin applied by using an aerosol repeatedly for 7 d after 2 weeks. Acetamide-45 at concentrations of 5, 10, or 30 mg/kg was then administered by intraperitoneal injection. Changes in dynamic lung compliance and lung resistance, the accumulation of inflammatory cells in bronchoalveolar lavage, PDE4 activity, and the concentration of interleukin-4 in rat lung tissue were determined. Seven days of treatment with acetamide-45 prevented eosinophil accumulation in allergic rats. At doses of 5, 10, and 30 mg/kg, acetamide-45 decreased lung resistance to 0.20+/-0.04, 0.25+/-0.07, and 0.22+/-0.05 cmH2O.s(-1).mL(-1), respectively (P<0.05 vs OVA), and it also increased dynamic lung compliance to 0.41+/-0.07, 0.39+/-0.06, and 0.42+/-0.09 mL/cmH2O (P<0.05 vs OVA). After being treated with different doses of acetamide-45, the PDE4 activities in lung tissue were 281+/-55, 273+/-57, and 238+/-36 nmol.g(-1).min( -1) (P<0.05 vs OVA), and the concentrations of interleukin-4 in lung tissue were 6.22+/-1.13, 5.95+/-1.20, and 5.68+/-2.20 microg/protein (P<0.05 vs OVA). Acetamide-45 was found to improve respiratory function and inhibit airway inflammation in this animal model, and the PDE4 activity of lung tissue was obviously inhibited. Acetamide-45 was an effective anti-inflammatory agent in respiratory inflammation, and the mechanism of its action might depend on inhibition of PDE4.

Elastase-induced changes in lung function: relationship to morphometry and effect of drugs

Intratracheal administration of porcine pancreatic elastase (PPE) produced a dose related decline in lung function, as assessed by changes in dynamic lung compliance (C dyn) in New Zealand White rabbits. This occured within 24 h of administration and persisted for 56 days ( n=6). These lung function changes were accompanied by histological evidence of emphysema in the lungs and were not mimicked by intratracheal administration of the proteolytic enzyme trypsin. Neither the lung function nor the histological changes induced by elastase could be prevented or reversed by either the glucocorticosteroid, dexamethasone, or all trans retinoic acid (ATRA). Our data suggest that local administration of elastase to the lungs of rabbits may provide a convenient way to assess the effects of drugs on the changes induced by elastase in airways.

Inhibitory mechanism of slowly adapting pulmonary stretch receptors after release from hyperinflation in anesthetized rabbits

In anesthetized, artificially ventilated rabbits with vagus nerve section, release from 10 consecutive hyperinflations (inflation volume = 3 tidal volume) caused an inhibition of the slowly adapting pulmonary stretch receptor (SAR) activity for 16–22 sec. Intravenous administration of tetraethylammonium (TEA, 10 and 20 mg/kg), a K + channel blocker, did not significantly alter either basal SAR discharge or tracheal pressure (P T). Although TEA treatment at 10.0 mg/kg had no significant effect on the magnitude and duration of inhibited SAR activity seen after release from hyperinflation, the increasing dose of this K + channel blocker up to 20 mg/kg inhibited these effects of the receptor activity but this inhibition was small. The Na +-K + ATPase inhibitor ouabain (5 and 10 μg/kg) that had no significant effect on SAR activity and P T in the control abolished or attenuated the inhibitory action of SARs in a dose-dependent manner. Furthermore, the changes in dynamic lung compliance (Cdyn) and P T in response to post-hyperinflation were not significantly influenced by pretreatment with either TEA or ouabain. These results suggest that the inhibitory action of receptors seen during post-hyperinflation corresponded with the induction of slow afterhyperpolarization (sAHP), and that the mechanism of generating the sAHP of SARs is mainly mediated by the activation of Na +-K + pump activity.

Respiratory and cardiovascular changes associated with toxic doses of a peptide antagonist of vasopressin in the rat

SK&F 101926 is a synthetic octapeptide which was designed to promote free water excretion by antagonizing the action of antidiuretic hormone. The clinical and pathologic changes in rats resulting from lethal doses of SK&F 101926 have suggested that death is associated with respiratory failure and/or cardiovascular collapse. To define the relationships between respiratory failure, cardiovascular collapse, and death, respiratory and cardiovascular parameters were monitored in anesthetized rats following the intravenous administration of SK&F 101926 at a dosage (3 mg/kg) which resulted in 70% mortality. Within 5 min after receiving this dosage, mean arterial blood pressure was reduced to values between 30 and 40 mm Hg in all rats. This degree of hypotension was well tolerated by some rats and, consequently, was not considered to be the cause of death. Deaths occurred between 9 and 58 min after dosing and were preceded by respiratory depression involving marked reductions in respiratory rate and the lack of compensatory increases in tidal volume. At the time of respiratory arrest, heart rates remained above 200 beats/min, mean arterial blood pressure remained between 30 and 40 mm Hg, and there were no consistent changes in dynamic lung compliance or total pulmonary resistance. Pretreatment of rats with a mast cell stabilizing agent (disodium cromoglycate), a mast cell degranulating agent (compound 48 80 ), or a histamine/5-hydroxytryptamine blocking agent (cyproheptadine) prevented the reductions in respiratory rate and death caused by SK&F 101926. These pretreatments also reduced the effect of SK&F 101926 on blood pressure, but were not able to completely prevent the hypotension. In conclusion, administration of SK&F 101926 can produce marked changes in respiratory and cardiovascular functions, with death appearing to be more closely associated with respiratory failure than with cardiovascular collapse. Furthermore, respiratory failure was not related to changes in the mechanical properties of the lung, and both the respiratory and cardiovascular changes which occurred following the administration of SK&F 101926 appear to be dependent on the release of mast cell mediators.

Effects of the PAF Antagonist WEB 2086 on PAF-induced Physiologic Alterations and on IgE Anaphylaxis in the Rabbit

The inhibitory effects of the specific platelet-activating factor (PAF) antagonist WEB 2086 on the in vivo PAF- and antigen-induced respiratory, circulatory, and hematologic alterations in the rabbit were investigated. WEB 2086 (600 micrograms/kg) given 5 min before challenge with 0.6 micrograms/kg of PAF completely inhibited the PAF-induced bronchoconstriction, period of rapid, shallow breathing, bradycardia, increase in right ventricular pressure, and hypotension. The PAF-induced thrombocytopenia, leukopenia, and basopenia were also prevented by WEB 2086 pretreatment. In contrast, the inhibitory effects of WEB 2086 on IgE anaphylaxis were much more limited. No significant inhibition of the responses in tidal volume, breathing frequency, hypotension, or bradycardia was observed in sensitized rabbits pretreated with 1 or 6 mg/kg of WEB 2086. However, WEB 2086 significantly inhibited the increase in total pulmonary resistance. Although the peak changes in dynamic lung compliance and right ventricular pressure were not or were only slightly inhibited by WEB 2086, a more rapid recovery to baseline was observed in rabbits receiving the PAF antagonist. No significant inhibition of the thrombocytopenia, leukopenia, and basopenia accompanying antigen challenge was observed in WEB 2086-pretreated rabbits. Pretreatment with the PAF antagonist prevented anaphylactic lethality. Thus, PAF appears to play a role in the lethality and the maximum increase in total pulmonary resistance of IgE systemic anaphylaxis but does not appear to be a major mediator of the other physiologic alterations, including systemic hypotension.

Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs

We examined the ability of rapidly adapting receptors (RARs) to monitor changes in dynamic lung compliance (Cdyn) in anesthetized spontaneously breathing dogs by recording RAR impulses from the vagus nerves. We decreased Cdyn in steps through the physiological range by briefly restricting lung expansion with an inflatable cuff around the chest and recording the response after deflating the cuff; we restored Cdyn to control by hyperinflating the lungs. Of 45 RARs, 34 were stimulated by a 40 +/- 2% reduction in Cdyn, their inspiratory discharge increasing on average more than threefold. Two-thirds of responsive RARs were stimulated by less than or equal to 20% reductions in Cdyn; in most, firing increased proportionately with lung stiffness (1/Cdyn) as Cdyn was decreased further. Stimulation by reduced Cdyn was not simply a function of the concomitant increase in transpulmonary pressure, because similar increases in pressure produced by increasing tidal volume produced smaller increases in firing. RAR stimulation was unaffected by atropine and, hence, was not dependent on neurally mediated changes in bronchomotor tone. Our results indicate that during spontaneous breathing RARs provide a signal inversely proportional to Cdyn.

Effect of cyclooxygenase and lipoxygenase products on pulmonary function in group B streptococcal sepsis.

The effects of the cyclooxygenase inhibitor, indomethacin, and the leukotriene receptor antagonist, FPL 57231, on changes in dynamic lung compliance and pulmonary resistance associated with a 1-h infusion of live group B streptococci were evaluated in mechanically ventilated piglets. To define mediators of early changes in lung function, animals were given an infusion of either FPL 57231 or indomethacin beginning 15 min after the infusion of group B streptococci was begun. These groups were compared to an untreated group who received only group B streptococci. Within 15 min of starting the bacterial infusion, all groups showed significant increases in pulmonary artery pressure, pulmonary artery wedge pressure, total pulmonary resistance, transpulmonary pressure, and thromboxane B2, and decreases in tidal volume, dynamic lung compliance, and PaO2. After treatment with indomethacin there were significant decreases in pulmonary artery pressure (mean +/- SEM; 48 +/- 1 to 22 +/- 3 mm Hg, p less than 0.001), pulmonary artery wedge pressure (7.5 +/- 1.3 to 2.2 +/- 0.4 mm Hg, p less than 0.001) and thromboxane B2 (6.51 +/- 1.56 to 1.01 +/- 0.27 ng/ml, p less than 0.01) and an increase in dynamic lung compliance (1.10 +/- 0.10 to 1.28 +/- 0.14 ml/cm H2O/kg, p less than 0.01) over the study period. Total pulmonary resistance decreased significantly (18.7 +/- 1.8 to 15.7 +/- 1.5 cm H2O/liter/s, p less than 0.02) only at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of lung stiffness on rapidly adapting receptors in rabbits and cats

We examined the response of rapidly adapting receptors (RARs) to changes in dynamic lung compliance (C dyn), recording vagal impulses in open-chest rabbits and cats with lungs ventilated at constant f and v t, and a positive end-expiratory pressure (PEEP) of 3–4 cm H 2O. After hyperinflation to produce maximal c dyn, most RARs fired irregularly and sparsely (< 1 impulse · sec 1). Reducing c dyn in steps by briefly removing PEEP progressively stimulated RARs during inflation, activity increasing sevenfold when c dyn was reduced by 40% ( P<0.0001). Reducing c dyn also increased RAR responses to static lung inflation. RAR stimulation by decreasing c dyn was virtually unaltered by atropine and hence was largely independent of reflex changes in bronchomotor tone. RARs were also stimulated by increasing vt at constant f, but, expressed as a function of airway pressure, the afferent response was less than that to increased lung stiffness (1/C dyn); expressed as a function of 1/c dyn, however, the responses were similar. We conclude that RARs signal increases in the force required to expand the lung, and speculate that their excitatory influence helps to maintain v t as the lungs become stiffen

Rapidly adapting receptor activity in dogs is inversely related to lung compliance.

We examined the response of pulmonary rapidly adapting receptors (RAR's) to changes in dynamic lung compliance (Cdyn) in the physiological range. RAR impulse activity was recorded from the cervical vagus nerves in anesthetized open-chest dogs whose lungs were ventilated at constant rate and tidal volume (VT), with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. After hyperinflation to produce maximal Cdyn, RAR's were silent or fired sparsely and irregularly. Reducing Cdyn in steps by briefly removing PEEP increased firing proportionately, and RAR's began to discharge vigorously in inflation. Activity was restored to control by hyperinflating the lungs. Activity also increased when we increased inflation rate, and hence the rate of change of airway pressure (dP/dt), by reducing inflation time, keeping VT and cycle length constant. RAR's were stimulated more when dP/dt was increased by reducing compliance than when dP/dt was increased by increasing inflation rate. We conclude that RAR's are sensitive to changes in Cdyn and speculate that excitatory input from RAR's may help to maintain VT as the lungs become stiffer.

Propranolol potentiates leukotriene D 4-induced bronchoconstriction and enhances antagonism by FPL 55712

Aerosol LTD 4-induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs was potentiated by either pretreatment with propranolol or bilateral adrenalectomy, whereas bilateral vagotomy did not affect the LTD 4 response. The dose-response curve describing LTD 4-induced changes in dynamic lung compliance (C D Y N) and pulmonary resistance (R L) [as reflective indices of bronchochonstriction] was shifted to the left by approximately 20-fold by propranolol. Against an equal degree of LTD 4-induced bronchoconstriction, the leukotriene antagonist, FPL 55712, had an apparent 20-fold greater potency in propranolol-pretreated animals vis a vis saline-treated controls. The duration of action of aerosol FPL 55712 was similar in both propranolol-treated and saline-treated animals. These results demonstrate that aerosol LTD 4-induced bronchoconstriction is modulated by an adrenergic compensatory bronchodilator mechanism that is apparently dependent upon the adrenals and independent of vagal influences. Inhibition of the effect of this reflex with propranolol also enhances the apparent potency of an aerosol leukotriene antagonist, FPL 55712, presumably reflecting a constant LTD 4 to antagonist ratio in the saline-treated and propranolol-pretreated guinea pigs.

Time-dependent carbon dioxide-induced changes in dynamic lung compliance

Time-dependent carbon dioxide-induced changes in dynamic lung compliance