Dynamic Respiratory Compliance Research Articles

The effect of fentanyl on immobility after noxious stimulation in isoflurane-anaesthetized pigs: Exploring the role of the serotonergic system

ObjectiveTo investigate if fentanyl induces immobility through activation of the serotonergic 5HT1A receptor, by using the 5HT1A-antagonist robalzotan. Study designA prospective, blinded, randomized, two-group study. AnimalsA group of 12 mixed-breed pigs aged 71–79 days. MethodsThe motor response to clamping a claw was assessed in isoflurane-anaesthetized pigs at baseline, then fentanyl was infused intravenously (IV) for 40 minutes and clamping was repeated. The infusion started at 20 μg kg–1 hour–1 and was increased by 60% until fentanyl produced immobility, defined as no motor response for 60 seconds. Subsequently, either robalzotan (1 mg kg–1) or the same volume of saline was injected IV and clamping was repeated. The change in response was compared with Fisher’s exact test. Mean arterial blood pressure (MAP) and heart rate (HR) were extracted for 2 minutes before and after 60 seconds of clamping, and the differences compared with a Wilcoxon signed-rank test. Dynamic respiratory compliance was calculated at baseline and after fentanyl; p < 0.05. ResultsBaseline clamping produced a motor response within 5 seconds. This was abolished by fentanyl. Robalzotan or saline did not alter this (p = 0.45). As a response to clamping, MAP and HR changed with median (range) –0.5 (–4.4 to 22.2) mmHg and –1 (–7 to 1.5), respectively, where HR changed significantly (p = 0.039). The 95% confidence interval for the effect size of fentanyl upon dynamic compliance was –3.25 to –1.65 mL cmH2O−1. Conclusions and clinical relevanceNo indication was found for the 5HT1A receptor to be involved in fentanyl-induced reduction of the motor response to claw clamping. The decreased compliance after fentanyl could suggest onset of chest wall rigidity.

LncRNA-AK007111 affects airway inflammation in asthma via the regulation of mast cell function.

Long noncoding RNAs (lncRNAs) are involved in gene transcription and pathophysiological processes of human diseases. Multiple lncRNAs have been shown to play important roles in the occurrence and development of asthma. This study aimed to explore the role of a novel lncRNA, lncRNA-AK007111, in asthma. Overexpression of lncRNA-AK007111 was induced in a mouse model of asthma via viral transfection, followed by the collection of alveolar lavage fluid and lung tissue for the detection of relevant inflammatory factors and pathological analysis of lung sections. Pulmonary resistance and respiratory dynamic compliance were measured using an animal pulmonary function analyzer. The number of mast cells sensitized by immunofluorescence was detected at the cellular level. The degree of degranulation of lncRNA-AK007111 after its knockdown was determined by detecting the level of β-hexosaminidase that was released and quantifying IL-6 and TNF-α using ELISA in a model of RBL-2H3 cells activated by immunoglobulin E plus antigen. Finally, we observed the migration ability of mast cells under a microscope. The results showed that in ovalbumin-sensitized mice, the upregulation of lncRNA-AK007111 promoted the infiltration of inflammatory cells in lung tissue, increased the number of total cells, eosinophils, and mast cells, upregulated IL-5 and IL-6 levels, and increased airway hyper-reactivity. Downregulation of lncRNA-AK007111 decreased the degranulation ability of IgE/Ag-activated mast cells and inhibited the expression of IL-6 and TNF-α; moreover, the migration ability of mast cells was significantly weakened. In conclusion, our study revealed that lncRNA-AK007111 plays an important role in asthma by modulating mast cell-related functions.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Effect of Body Posture on Lung Ventilation and Oxygenation During Carbon Dioxide Pneumoperitoneum in Rabbit

This study was conducted to investigate the influence of body position on respiratory compliance and oxygenation during iatrogenic pneumoperitoneum in the rabbit. The peak inspiratory pressure, dynamic compliance, static compliance and arterial gas parameters were calculated and measured 10 min before and 30 min after the creation of pneumoperitoneum with the patient in the horizontal position, 30 min after placing the patient in the Trendelenburg position and 30 min after placing the patient in the reversed Trendelenburg position. Following the creation of pneumoperitoneum and Trendelenburg positioning, there was a significant increase in peak inspiratory pressure while dynamic and static respiratory compliance decreased. Similarly, arterial oxygenation increased during Trendelenburg position while arterial carbon pressure remained within limits during all positions. Overall, the reverse Trendelenburg position did not improve ventilation, neither the oxygenation. However, this position showed to be more appropriate because may reduce the risk of lung injury associated with high-pressure ventilation during pneumoperitoneum.

Increased effort during partial ventilatory support is not associated with lung damage in experimental acute lung injury

BackgroundAn on-going debate exists as to whether partial ventilatory support is lung protective in an acute phase of ARDS. So far, the effects of different respiratory efforts on the development of ventilator-associated lung injury (VALI) have been poorly understood.To test the hypothesis whether respiratory effort itself promotes VALI, acute lung injury (ALI) was induced in 48 Sprague Dawley rats by hydrochloric acid aspiration model. Hemodynamics, gas-exchange, and respiratory mechanics were measured after 4 h of ventilation in pressure control (PC), assist-control (AC), or pressure support with 100% (PS100), 60% (PS60), or 20% (PS20) of the driving pressure during PC. VALI was assessed by histological analysis and biological markers.ResultsALI was characterized by a decrease in PaO2/FiO2 from 447 ± 75 to 235 ± 90 mmHg (p < 0.001) and dynamic respiratory compliance from 0.53 ± 0.2 to 0.28 ± 0.1 ml/cmH2O (p < 0.001). There were no differences in hemodynamics or respiratory function among groups at baseline or after 4 h of ventilation. The reduction of mechanical pressure support was associated with a compensatory increase in an inspiratory effort such that peak inspiratory transpulmonary pressures were equal in all groups. The diffuse alveolar damage score showed significant lung injury but was similar among groups. Pro- and anti-inflammatory proteins in the bronchial fluid were comparable among groups.ConclusionsIn experimental ALI in rodents, the respiratory effort was increased by reducing the pressure support during partial ventilatory support. In the presence of a constant peak inspiratory transpulmonary pressure, an increased respiratory effort was not associated with worsening ventilator-associated lung injury measured by histologic score and biologic markers.

Visual function scale for identification of infants with low respiratory compliance

Precise estimation of respiratory function is essential to optimise neonatal respiratory care. However, current clinical scores have not been validated with quantitative measures of respiratory function. The aim of this study was to develop a physiological scoring system to predict low respiratory dynamic compliance of <0.6ml/cmH2O/kg. Forty-four newborn infants were studied before (dynamic compliance) and shortly after scheduled extubation (physiological signs). A novel scoring system was developed based on the association between physiological signs and dynamic compliance. The respiratory rate was identified as the primary independent variable for dynamic compliance in the univariate analysis. The prediction score for low dynamic compliance comprised the presence of nasal flaring, see-saw respiration, suprasternal/intercostal retraction, and the respiratory rate ranks (0-3). The area under the receiver-operating characteristics curve of the composite score had discriminatory capability of 0.86 (95% confidence interval: 0.75-0.97) to predict low dynamic compliance with the optimal cut-off value of ≥3 (sensitivity, 0.882; specificity, 0.667). Our novel scoring system might help predict newborn infants with low dynamic compliance, who may require escalation of respiratory support, or transfer to higher level units.

Application of dead space fraction to titrate optimal positive end-expiratory pressure in an ARDS swine model.

This study aimed to apply the dead space fraction [ratio of dead space to tidal volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models of ARDS were constructed. A lung recruitment maneuver was then conducted and the PEEP was set at 20 cm H2O. The PEEP was reduced by 2 cm H2O every 10 min until 0 cm H2O was reached, and VD/VT was measured after each decrement step. VD/VT was measured using single-breath analysis of CO2, and calculated from arterial CO2 partial pressure (PaCO2) and mixed expired CO2 (PeCO2) using the following formula: VD/VT = (PaCO2 - PeCO2)/PaCO2. The optimal PEEP was identified by the lowest VD/VT method. Respiration and hemodynamic parameters were recorded during the periods of pre-injury and injury, and at 4 and 2 cm H2O below and above the optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25±1.36 cm H2O. During the Po period, VD/VT decreased to a lower value (0.44±0.08) compared with that during the injury period (0.68±0.10) (P<0.05), while the intrapulmonary shunt fraction reached its lowest value. In addition, a significant change of dynamic tidal respiratory compliance and oxygenation index was induced by PEEP titration. These results indicate that minimal VD/VT can be used for PEEP titration in ARDS.

Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

Automated Rotational Percussion Bed and Bronchoscopy Improves Respiratory Mechanics and Oxygenation in ARDS Patients Supported with Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been used to provide "lung rest" through the use of low tidal volume (6 ml/kg) and ultralow tidal volume (<6 ml/kg) ventilation in acute respiratory distress syndrome (ARDS). Low and ultralow tidal volume ventilation can result in low dynamic respiratory compliance and potentially increased retention of airway secretions. We present our experience using automated rotational percussion beds (ARPBs) and bronchoscopy in four ARDS patients to manage increased pulmonary secretions. These beds performed automated side-to-side tilt maneuver and intermittent chest wall percussion. Their use resulted in substantial reduction in peak and plateau pressures in two patients on volume control ventilation, while the driving pressures (inspiratory pressure) to attain the desired tidal volumes in patients on pressure control ventilation also decreased. In addition, mean partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio (109 pre-ARPB vs. 157 post-ARPB), positive end-expiratory pressure (10 cm H2O vs. 8 cm H2O), and FiO2 (0.88 vs. 0.52) improved after initiation of ARPB. The improvements in the respiratory mechanics and oxygenation helped us to initiate early ECMO weaning. Based on our experience, the use of chest physiotherapy, frequent body repositioning, and bronchoscopy may be helpful in the management of pulmonary secretions in patients supported with ECMO.

Justification for Chest Physiotherapy during Ultra‐Protective Lung Ventilation and Extra‐Corporeal Membrane Oxygenation: A Case Study

This case report describes the chest physiotherapy (CPT) intervention provided to a 32-year old man with severe respiratory failure undergoing extra-corporeal membrane oxygenation (ECMO) support and ultra-protective ventilatory strategy. Low tidal volume ventilation when used in patients with extremely low dynamic respiratory compliance may predispose the patient to secretion retention, and the role of CPT in this setting is unclear. The method used is a single subject case report. Written consent obtained from patient's representative. Secretion clearance in this patient was initially limited to suctioning; however, after developing major airway occlusion secondary to impacted secretions, he received intensive CPT consisting of positioning, ventilator hyperinflation, expiratory chest wall shaking and suctioning. After 13 days of two to three times daily CPT, the patient weaned from ECMO support. Regular CPT may have facilitated secretion clearance and lung recovery in this patient. Future research should investigate the optimal CPT techniques for patients with sub-dead space tidal ventilation and extremely low dynamic respiratory compliance during ECMO with ultra-protective ventilatory strategy (UPVS).

The Impacts of Super Obesity Versus Morbid Obesity on Respiratory Mechanics and Simple Hemodynamic Parameters During Bariatric Surgery

This study was designed to determine the impact of the degree of obesity on respiratory mechanics and simple hemodynamic parameters at laparoscopic bariatric surgery. The patients were divided into two groups, each of which included 24 patients (a morbidly obese group and a super obese group) undergoing laparoscopic bariatric surgery. Dynamic respiratory compliance, respiratory resistance, and peak inspiratory pressures were measured at four time points: 10 min after anesthesia induction (T1: induction), 10 min after pneumoperitoneum (T2: pneumoperitoneum), 10 min after terminating pneumoperitoneum (T3: end-pneumoperitoneum), and before extubation (T4: extubation). The systolic, diastolic, and mean arterial pressures and the heart rate values were measured noninvasively in T0 (10 min before operation). Obesity was found to cause a statistically significant increase in respiratory resistance and a peak inspiratory pressure and a decrease in dynamic respiratory compliance. In the morbidly obese group, the lowest dynamic respiratory compliance was 37 ± 12 mL/cm H(2)O, but it was 33 ± 13 mL/cm H(2)O in the super obese group. The systolic pressure, diastolic pressure, and mean arterial pressure were found to decrease significantly in both groups. Morbid obesity and super obesity have negative effects on hemodynamics and respiratory mechanics.

Effects of respiratory mechanics on the capnogram phases: importance of dynamic compliance of the respiratory system

IntroductionThe slope of phase III of the capnogram (SIII) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. SIII depends not only on the airway geometry, but also on the dynamic respiratory compliance (Crs); this latter effect has not been evaluated. Accordingly, we established the value of SIII for monitoring airway resistance during mechanical ventilation.MethodsSidestream capnography was performed during mechanical ventilation in patients undergoing elective cardiac surgery (n = 144). The airway resistance (Raw), total respiratory resistance and Crs displayed by the ventilator, the partial pressure of arterial oxygen (PaO2) and SIII were measured in time domain (ST-III) and in a smaller cohort (n = 68) by volumetry (SV-III) with and without normalization to the average CO2 phase III concentration. Measurements were performed at positive end-expiratory pressure (PEEP) levels of 3, 6 and 9 cmH2O in patients with healthy lungs (Group HL), and in patients with respiratory symptoms involving low (Group LC), medium (Group MC) or high Crs (Group HC).ResultsST-III and SV-III exhibited similar PEEP dependencies and distribution between the protocol groups formed on the basis of Crs. A wide interindividual scatter was observed in the overall Raw-ST-III relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in SIII in Group HC, and in moderate decreases in SIII in Group MC, whereas ST-III was insensitive to changes in airway caliber in Groups LC and HL.ConclusionsSIII assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although ST-III may be of value for bedside monitoring of the airway properties, its sensitivity depends on Crs. Thus, assessment of the capnogram shape should always be coupled with Crs when the airway resistance or oxygenation are evaluated.

Case–control study of respiratory dynamic compliance in mechanically ventilated near-term newborns in a pre-hospital setting

To determine the threshold value between normal or decreased dynamic compliance (Cdyn) in ventilated near-term newborns. A case control study was performed during pediatric transport. Controls were newborns without pulmonary disease (group 1; n=30) and cases were newborns with respiratory distress syndrome, the paradigm of decreased Cdyn (group 2; n=30). All consecutive newborns of more than 34weeks' gestation and less than 5 days of life, intubated and ventilated with Babylog 8,000 plus (Dräger, Lübeck, Germany) were included from February 2008 to June 2010. Newborns were assigned to groups 1, 2, or 3 (other patients with disease where the compliance is not easily predictable) by two physicians, using predefined criteria. Cdyn was as measured by the ventilator in spontaneous mandatory ventilation mode with less than 15% leaks. One hundred and twelve newborns were included in the study. In the multivariate analysis, the groups of diseases and height were statistically associated with Cdyn (p<0.001). The receiver operating characteristic curve of Cdyn corrected for height constructed with group 1 and 2 newborns yielded a cutoff value of 2.02mL/mbar/m with a sensitivity of 100% (95% confidence interval [100-100%]) and a specificity of 96% (95% confidence interval [90-100%]) to differentiate between group 1 and 2 newborns. Ventilator-measured dynamic compliance can differentiate normal and decreased compliance in near-term newborns of more than 34weeks' gestation in the clinical setting.

A comparison of methods to identify open-lung PEEP

Many methods exist in the literature for identifying PEEP to set in ARDS patients following a lung recruitment maneuver (RM). We compared ten published parameters for setting PEEP following a RM. Lung injury was induced by bilateral lung lavage in 14 female Dorset sheep, yielding a PaO(2) 100-150 mmHg at F(I)O(2) 1.0 and PEEP 5 cmH(2)O. A quasi-static P-V curve was then performed using the supersyringe method; PEEP was set to 20 cmH(2)O and a RM performed with pressure control ventilation (inspiratory pressure set to 40-50 cmH(2)O), until PaO(2) + PaCO(2) > 400 mmHg. Following the RM, a decremental PEEP trial was performed. The PEEP was decreased in 1 cmH(2)O steps every 5 min until 15 cmH(2)O was reached. Parameters measured during the decremental PEEP trial were compared with parameters obtained from the P-V curve. For setting PEEP, maximum dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), and minimum shunt calculated during the decremental PEEP trial, and the lower Pflex and point of maximal compliance increase on the inflation limb of the P-V curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained using the deflation upper Pflex and the point of maximal compliance decrease on the deflation limb were significantly higher, and the true inflection point on the inflation limb and minimum PaCO(2) were significantly lower than the other variables. In this animal model of ARDS, dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), minimum shunt, inflation lower Pflex and Pmci,i yield similar values for PEEP following a recruitment maneuver.

Respiratory and hemodynamic changes during decremental open lung positive end-expiratory pressure titration in patients with acute respiratory distress syndrome

IntroductionTo investigate haemodynamic and respiratory changes during lung recruitment and decremental positive end-expiratory pressure (PEEP) titration for open lung ventilation in patients with acute respiratory distress syndrome (ARDS) a prospective, clinical trial was performed involving 12 adult patients with ARDS treated in the surgical intensive care unit in a university hospital.MethodsA software programme (Open Lung Tool™) incorporated into a standard ventilator controlled the recruitment (pressure-controlled ventilation with fixed PEEP at 20 cmH2O and increased driving pressures at 20, 25 and 30 cmH2O for two minutes each) and PEEP titration (PEEP lowered by 2 cmH2O every two minutes, with tidal volume set at 6 ml/kg). The open lung PEEP (OL-PEEP) was defined as the PEEP level yielding maximum dynamic respiratory compliance plus 2 cmH2O. Gas exchange, respiratory mechanics and central haemodynamics using the Pulse Contour Cardiac Output Monitor (PiCCO™), as well as transoesophageal echocardiography were measured at the following steps: at baseline (T0); during the final recruitment step with PEEP at 20 cmH2O and driving pressure at 30 cmH2O, (T20/30); at OL-PEEP, following another recruitment manoeuvre (TOLP).ResultsThe ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) increased from T0 to TOLP (120 ± 59 versus 146 ± 64 mmHg, P < 0.005), as did dynamic respiratory compliance (23 ± 5 versus 27 ± 6 ml/cmH2O, P < 0.005). At constant PEEP (14 ± 3 cmH2O) and tidal volumes, peak inspiratory pressure decreased (32 ± 3 versus 29 ± 3 cmH2O, P < 0.005), although partial pressure of arterial carbon dioxide (PaCO2) was unchanged (58 ± 22 versus 53 ± 18 mmHg). No significant decrease in mean arterial pressure, stroke volume or cardiac output occurred during the recruitment (T20/30). However, left ventricular end-diastolic area decreased at T20/30 due to a decrease in the left ventricular end-diastolic septal-lateral diameter, while right ventricular end-diastolic area increased. Right ventricular function, estimated by the right ventricular Tei-index, deteriorated during the recruitment manoeuvre, but improved at TOLP.ConclusionsA standardised open lung strategy increased oxygenation and improved respiratory system compliance. No major haemodynamic compromise was observed, although the increase in right ventricular Tei-index and right ventricular end-diastolic area and the decrease in left ventricular end-diastolic septal-lateral diameter during the recruitment suggested an increased right ventricular stress and strain. Right ventricular function was significantly improved at TOLP compared with T0, although left ventricular function was unchanged, indicating effective lung volume optimisation.

Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia

Bronchopulmonary dysplasia (BPD) is characterised by impaired alveolarisation, inflammation and aberrant vascular development. Phosphodiesterase (PDE) inhibitors can influence cell proliferation, antagonise inflammation and restore vascular development and homeostasis, suggesting a therapeutic potential in BPD. The aim of the present study was to investigate PDE expression in the lung of hyperoxia-exposed mice, and to assess the viability of PDE4 as a therapeutic target in BPD. Newborn C57BL/6N mice were exposed to normoxia or 85% oxygen for 28 days. Animal growth and dynamic respiratory compliance were reduced in animals exposed to hyperoxia, paralleled by decreased septation, airspace enlargement and increased septal wall thickness. Changes were evident after 14 days and were more pronounced after 28 days of hyperoxic exposure. At the mRNA level, PDE1A and PDE4A were upregulated while PDE5A was downregulated under hyperoxia. Immunoblotting confirmed these trends in PDE4A and PDE5A at the protein expression level. Treatment with cilomilast (PDE4 inhibitor, 5 mg.kg(-1).day(-1)) between days 14 and 28 significantly decreased the mean intra-alveolar distance, septal wall thickness and total airspace area and improved dynamic lung compliance. Pharmacological inhibition of phosphodiesterase improved lung alveolarisation in hyperoxia-induced bronchopulmonary dysplasia, and thus may offer a new therapeutic modality in the clinical management of bronchopulmonary dysplasia.

Effects of Pneumoperitoneum and Positioning on Respiratory Mechanics in Chronic Obstructive Pulmonary Disease Patients During Nissen Fundoplication

The aim of this study was to evaluate the effects of pneumoperitoneum and patient positioning on respiratory mechanics and blood gases in chronic obstructive pulmonary disease (COPD) patients during laparoscopic Nissen fundoplication. After the approval of the Ethical Committee, 32 patients were divided into 2 groups as COPD patients (n=16) and normal patients (n=16). Dynamic respiratory compliance (Cdyn), airway resistance, and peak inspiratory pressure were monitored. Measurements were made in 5 time points: after intubation (intubation), Trendelenburg position (Trendelenburg), during laparoscopic Nissen fundoplication surgery after pneumoperitoneum with the Fowler position (Fowler), right before the desufflation with Fowler position (Fowler-end), and after the desufflation in supine position (supine). Samples of arterial blood gases were collected at the same periods. At all periods, there was a significant decrease in Cdyn and arterial oxygen pressure in 2 groups. Although pneumoperitoneum did not exist during Trendelenburg position, the Cdyn (38+/-13 mL cm H2O(-1)) found to be significantly decreased in COPD patients. In 2 groups, the lowest Cdyn value detected during the Fowler-end period was 43+/-8 mL cm H2O(-1) in control group and 34+/-11 mL cm H2O(-1) in COPD group. Whereas the pH decreased at Fowler, Fowler-end, and supine period, arterial carbon dioxide pressure increased (P<0.05). There was no difference for the other parameters. In COPD patients, Trendelenburg position has negative effect on respiratory mechanics. Pneumoperitoneum and other positions have similar effect on respiratory mechanics in COPD and control patients.

Effect of inhalation of nebulized NO donor substance on acute hypoxic lung injury in newborn piglets

Birth asphyxia may result in multiple organ dysfunction such as lung injury. Inhalation of nebulized nitric oxide precursor can selectively reduce pulmonary hypertension. However, it is unknown whether such precursors can alleviate lung injury induced by hypoxia. We evaluated the effect of inhalation of nebulized nitroglycerine and sodium nitroprusside on acute hypoxic lung injury in newborn piglets. Acute hypoxic lung injury was induced by inspiring 10% O2 for 1 hour. Twenty-four anaesthetized and mechanically ventilated piglets (5-7 days old) were randomly divided into four groups: (1) group S, not hypoxic; (2) group C, nebulized saline after hypoxia; (3) group NTG, nebulized nitroglycerine after hypoxia; (4) group SNP, nebulized sodium nitroprusside after hypoxia. Respiratory dynamic compliance and resistance of respiratory system were recorded at baseline, 0.5 hour and 1 hour of hypoxia; then 0.5 hour, 1 hour, 3 hours and 5 hours following hypoxia. After nebulization, arterial blood was collected for measuring methaemoglobin and nitrate/nitrite levels. Right lung tissue, wet-dry ratio and myeloperoxidase level were determined. White blood cell count (WBC), total surfactant phospholipids (TPL) and disaturated phosphatidyl choline (DSPC) of the bronchoalveolar lavage fluid (BALF) were calculated. Left lungs were used for examining pathological changes. No significant difference was observed in respiratory dynamic compliance, resistance of respiratory system, wet-dry ratio, levels of methaemoglobin and nitrate/nitrite after nebulization, TPL or DSPC/TPL among four groups. WBC in BALF in groups NTG and SNP significantly decreased as compared with group C: similarly for myeloperoxidase level in lung tissue. Lung histological findings showed infiltration of neutrophils in groups NTG and SNP decreased significantly as compared with group C. Inhalation of nebulized nitroglycerine or sodium nitroprusside can alleviate the infiltration of neutrophils, while it affects neither the metabolism of phospholipids nor water content in the lungs.

Measurement and Inhibition of Airway Hyperreactivity in a Guinea Pig Model of Allergic Asthma

An accurate invasive technique to measure airway hyperreactivity (AHR) in a guinea pig model of asthma is described. Previous reports of the use of flexi‐Vent, a computer controlled, small animal ventilator using forced oscillation techniques have been limited to the mouse. Dexamethasone and an H4R antagonist, JNJ‐7777120, were investigated for their ability to attenuate the AHR response which was induced by systemic sensitization and aerosol challenge with ovalbumin (OVA). To attenuate the response, guinea pigs were dosed around aerosol challenge with JNJ‐7777120 or dexamethasone. Twenty‐four hours post challenge airway hyperreactivity (AHR) was measured. AHR was assessed by measuring changes in dynamic respiratory resistance (R) and compliance (C), in response to rising doses of aerosolized methacholine (Mch), in anaesthetized animals. AHR was induced by Mch in a dose dependent manner as shown by an increase in R and decrease in C. JNJ‐7777120 and dexamethasone inhibited the increase in R and decrease in C dose dependently. Measurement and pharmacological modulation of AHR responses to Mch are therefore detectable using this technique. The novel method described allows for the accurate measurement of airway hyperreactivity a major clinical hallmark of asthma and has utility in the assessment of potential therapies for lung disease.

Correlação dos achados tomográficos com parâmetros de função pulmonar na fibrose pulmonar idiopática em não fumantes

To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography (HRCT) findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF(25-75%)/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans.