Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome

BACKGROUND:

Animal experiments showed that recruitment maneuver (RM) and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS).

METHODS:

Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index (PaO₂/FiO₂), peak inspiratory pressure (PIP), Plateau pressure (Pplat), static pulmonary compliance (Cst) and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student''s t test and Fisher''s exact test were used to process the data.

RESULTS:

The levels of PaO₂/FiO₂ and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group (P<0.05). The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group (P<0.05). The EVLWI in the two groups showed downward trend after treatment (P<0.05), and the differences were signifcant at all time points (P<0.01); the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours (P<0.05 or P<0.01). Compared with pre-RM, hemodynamics changes during RM were significantly different (P<0.01); compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM (P>0.05).

CONCLUSIONS:

RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.KEY WORDS: Lung recruitment maneuver, Acute respiratory distress syndrome, Respiratory mechanics, Extravascular lung water index, Hemodynamics, Lung protective ventilation, Oxygenation index     

Effects of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome

BACKGROUND:

Pulmonary stretch reflex plays an important role in regulation of respiratory movement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome (ARDS).

METHODS:

ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilated with neurally adjusted ventilatory assistance (NAVA) with a tidal volume (V_T) of 6 mL/kg and the electrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation of the bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM) group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanics were detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively. Pulmonary permeability index, pathological changes and inflammatory response were also measured.

RESULTS:

Compared with the SHAM group, PaO₂/FiO₂ in the VAG group decreased significantly 2 and 3 hours after ventilation (P<0.05). There was no significant difference in PaCO₂ between the SHAM and VAG groups (P>0.05), and the VAG group had a high V_T, peak pressure (Ppeak), and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P<0.05). Compared to the SHAM group, dead space fraction (V_D/V_T) and respiratory system elastance (Ers) in the VAG group increased (P<0.05) and static pulmonary compliance (Cst) decreased markedly (P<0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injury score (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-α (TNF-α) (779±372 pg/mL vs. 355±130 pg/mL) and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG group compared with the SHAM group (P<0.05).

CONCLUSION:

Lung injury is aggravated after bilateral vagotomy, demonstrating that pulmonary stretch reflex may have protective effect on the lung.KEY WORDS: Pulmonary stretch reflex, Vagus nerve, Lung injury, Acute respiratory distress syndrome, Electrical activity of diaphragm, Mechanical ventilation     

Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation

BACKGROUND:

Early withdrawal of invasive mechanical ventilation (IMV) followed by noninvasive MV (NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with acute respiratory failure (ARF). Using pulmonary infection control window (PIC window) as the switch point for transferring from invasive to noninvasive MV, the time for early extubation can be more accurately judged, and therapy efficacy can be improved. This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy (FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV.

METHODS:

Since July 2006 to January 2011, 106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization. Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used (group A, n=54) or not (group B, n=52) during sequential weaning from invasive to noninvasive MV. In group A, for sputum suction and bronchoalveolar lavage (BAL), a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube, which was accompanied with uninterrupted use of a ventilator. After achieving PIC window, patients of both groups changed to NIMV mode, and weaned from ventilation. The following listed indices were used to compare between the groups after treatment: 1) the occurrence time of PIC, the duration of MV, the length of ICU stay, the success rate of weaning from MV for the first time, the rate of reventilation and the occurrence rate of ventilator-associated pneumonia (VAP); 2) the convenience and safety of FOB manipulation. The results were compared using Student’s t test and the Chi-square test.

RESULTS:

The occurrence time of PIC was (5.01±1.49) d, (5.87±1.87) d in groups A and B, respectively (P<0.05); the duration of MV was (6.98±1.84) d, (8.69±2.41) d in groups A and B, respectively (P<0.01); the length of ICU stay was (9.25±1.84) d, (11.10±2.63) d in groups A and B, respectively (P<0.01); the success rate of weaning for the first time was 96.30%, 76.92% in groups A and B, respectively (P<0.01); the rate of reventilation was 5.56%, 19.23% in groups A and B, respectively (P<0.05); and the occurrence rate of VAP was 3.70%, 23.07% in groups A and B, respectively (P<0.01). Moreover, it was easy and safe to manipulate FOB, and no side effect was observed.

CONCLUSIONS:

The application of FOB in patients with AECOPD during sequential weaning of invasive-noninvasive MV is effective in ICU. It can decrease the duration of MV and the length of ICU stay, increase the success rate from weaning MV for the first time, reduce the rate of reventilation and the occurrence rate of VAP. In addition, such a method is convenient and safe in patients of this kind.KEY WORDS: Acute exacerbations of chronic obstructive pulmonary disease, Acute respiratory failure, Mechanical ventilation, Sequential weaning of invasive-noninvasive ventilation, Fiberoptic bronchscopy, Bronchoalveolar lavage, Pulmonary infection control window, Side effect, Success rate     

Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition

Introduction

The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity.

Methods

The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe.

Results

Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO₂/FIO₂ ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO₂/FIO₂ ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO₂/FIO₂ ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001).

Conclusions

Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability.

Trial registration

UMIN-CTR ID UMIN000003627     

Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator-induced lung injury

Introduction

Endothelial cell injury is an important component of acute lung injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane protein that connects endothelial cells to one another and can be detected as a soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial cells resulting in increasing sPECAM1 levels in the systemic circulation.

Methods

We studied 36 Sprague–Dawley rats in two prospective, randomized, controlled studies (healthy and septic) using established animal models of ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to spontaneous breathing or two MV strategies: low tidal volume (V_T) (6 ml/kg) and high-V_T (20 ml/kg) on 2 cmH₂O of positive end-expiratory pressure (PEEP). In low-V_T septic animals, 10 cmH₂O of PEEP was applied. We performed pulmonary histological and physiological evaluation and measured lung PECAM1 protein content and serum sPECAM1 levels after four hours ventilation period.

Results

High-V_T MV caused severe lung injury in healthy and septic animals, and decreased lung PECAM1 protein content (P < 0.001). Animals on high-V_T had a four- to six-fold increase of mean sPECAM1 serum levels than the unventilated counterpart (35.4 ± 10.4 versus 5.6 ± 1.7 ng/ml in healthy rats; 156.8 ± 47.6 versus 35.6 ± 12.6 ng/ml in septic rats) (P < 0.0001). Low-V_T MV prevented these changes. Levels of sPECAM1 in healthy animals on high-V_T MV paralleled the sPECAM1 levels of non-ventilated septic animals.

Conclusions

Our findings suggest that circulating sPECAM1 may represent a promising biomarker for the detection and monitoring of ventilator-induced lung injury.     

Protective effect of glutamine in critical patients with acute liver injury

BACKGROUND:

Glutamine (Gln) supplementation is known to decrease oxidative stress and inflammatory response, enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was undertaken to evaluate the relationship between the effect of early parenteral glutamine (Gln) supplement on acute liver injury (ALI) and heat shock protein 70 (HSP-70) expression in critical patients.

METHODS:

Forty-four patients who had been admitted to the emergency intensive care unit (EICU) of Nanjing First Hospital Affiliated to Nanjing Medical University were randomly divided into a control group (n=22) and a Gln group (n=22). The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gln 0.4 g/kg per day was given for 7 days in the Gln group. Serum HSP-70 and Gln were measured at admission and at 7 days after admission. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL), serum levels of HSP-70 and Gln, mechanical ventilation (MV) time, ICU stay, peripheral blood of TNF-α, IL-6, CD3, CD4 and CD4/CD8 levels were also measured in the two groups.

RESULTS:

In the Gln group, the levels of serum HSP-70 and Gln were significantly higher after Gln treatment than those before the treatment (P<0.01). HSP-70 level was positively correlated with the Gln level in the Gln group after administration of parenteral Gln (P<0.01). The levels of serum ALT, AST, TBiL and TNF-α, IL-6 were lower in the Gln group than in the non-Gln group (P<0.01). MV time and ICU stay were significantly different between the two groups (P<0.05). The levels of CD3, CD4 and CD4/CD8 were significantly higher in the Gln group than in the control group after treatment (P<0.05).

CONCLUSION:

Parenteral Gln significantly increases the level of serum HSP70 in critically ill patients. The enhanced expression of HSP70 is correlated with improved outcomes of Gln-treated patients with acute liver injury.KEY WORDS: Glutamine, Heat shock protein, Critically ill patients, Acute liver injury     

Effects of bone marrow-derived mesenchymal stem cells engraftment on vascular endothelial cell growth factor in lung tissue and plasma at early stage of smoke inhalation injury

BACKGROUND:

This study was undertaken to determine the effect of mesenchymal stem cells (MSCs) engraftment on vascular endothelial cell growth factor (VEGF) in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.

METHODS:

A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly: a control group (S group, n=32) and a MSCs treatment group (M group, n=32). 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×10⁷/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 (baseline), 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.

RESULTS:

In the lung tissue, VEGF decreased gradually in the S group (P<0.05) and significantly decreased in the M group (P<0.05), but it increased more significantly than the values at the corresponding time points (P<0.05). In peripheral blood, VEGF increased gradually in the S group (P<0.05) and markedly increased in the M group (P<0.05), but it decreased more significantly than the values at corresponding time points (P<0.05).

CONCLUSION:

MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.KEY WORDS: Mesenchymal stem cells, Smoke inhalation injury, Vascular endothelial cell growth factor, Extravascular lung water, Rabbit     

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin

Introduction

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia.

Methods

We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation.

Results

In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1–3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut).

Conclusions

MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.     

Effects of dynamic ventilatory factors on ventilator-induced lung injury in acute respiratory distress syndrome dogs

BACKGROUND:

Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome (ARDS) including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries (VILI) and to explore its potential mechanisms.

METHODS:

Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.

RESULTS:

IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-α ray degree of group B was significantly higher than that in the other groups (P<0.01), especially in group C (P>0.05). The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.

CONCLUSION:

Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of pro-inflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.KEY WORDS: Acute respiratory distress syndrome, Dynamic factors, Inspiratory flow, Ventilator-induced lung injury     

Exhaled nitric oxide in neonates with or without hypoxemic respiratory failure

BACKGROUND:

Exhaled nitric oxide (eNO) is one of the airway condensate derived markers, reflecting mainly airway inflammation in asthma and other lung diseases. The changes of eNO levels as pathophysiology of neonatal hypoxemic respiratory failure (HRF) in early postnatal life have not been thoroughly studied. The present study was to establish a method for measuring eNO concentrations in neonates with or without HRF.

METHODS:

Twenty-two newborn infants with HRF and 26 non-NRF controls were included within the first 24 hours of postnatal life. Their eNO levels were detected with a rapid-response chemiluminescence analyzer daily during the first week of their postnatal life, and lung mechanics and gas exchange efficiency were monitored at the same time, such as pulse oxygen saturation (SpO₂), inspired fraction of oxygen (FiO₂) and other parameters.

RESULTS:

During the first two days of postnatal life, eNO values of HRF neonates were significantly higher than those of the control neonates (day 1, 7.9±3.2 vs. 5.8±1.8 parts per billion [ppb], P<0.05; day 2, 8.8±3.2 vs. 6.0±2.4 ppb, P<0.05), but there were no significant differences in the following days. With SpO₂/FiO₂ increasing, difference of eNO values between the HRF and non-HRF neonates became narrowed, but there was still a two-fold difference of eNO/[SpO₂/(FiO₂×100)] on days 5-7.

CONCLUSION:

We established a method for measuring eNO and found difference in neonates with or without HRF, which diminished with prolonged postnatal days, reflecting pathophysiological characteristics of HRF.KEY WORDS: Neonates, Respiratory failure, Respiratory therapy, Nitric oxide, Respiratory physiology, Nitric oxide synthase     

Effects of ventilation strategy on distribution of lung inflammatory cell activity

Introduction

Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin administration.

Methods

Anesthetized sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either injurious or protective mechanical ventilation (n = 6 per group). We used positron emission tomography to obtain images of regional perfusion and shunting with infused ¹³N[nitrogen]-saline and images of neutrophilic inflammation with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). The Sokoloff model was used to quantify ¹⁸F-FDG uptake (K_i), as well as its components: the phosphorylation rate (k₃, a surrogate of hexokinase activity) and the distribution volume of ¹⁸F-FDG (F_e) as a fraction of lung volume (K_i = F_e × k₃). Regional gas fractions (f_gas) were assessed by examining transmission scans.

Results

Before endotoxin administration, protective (vs. injurious) ventilation was associated with a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO₂/FiO₂) (351 ± 117 vs. 255 ± 74 mmHg; P < 0.01) and higher whole-lung f_gas (0.71 ± 0.12 vs. 0.48 ± 0.08; P = 0.004), as well as, in dependent regions, lower shunt fractions. Following 2 h of endotoxemia, PaO₂/FiO₂ ratios decreased in both groups, but more so with injurious ventilation, which also increased the shunt fraction in dependent lung. Protective ventilation resulted in less nonaerated lung (20-fold; P < 0.01) and more normally aerated lung (14-fold; P < 0.01). K_i was lower during protective (vs. injurious) ventilation, especially in dependent lung regions (0.0075 ± 0.0043/min vs. 0.0157 ± 0.0072/min; P < 0.01). ¹⁸F-FDG phosphorylation rate (k₃) was twofold higher with injurious ventilation and accounted for most of the between-group difference in K_i. Dependent regions of the protective ventilation group exhibited lower k₃ values per neutrophil than those in the injurious ventilation group (P = 0.01). In contrast, F_e was not affected by ventilation strategy (P = 0.52). Lung neutrophil counts were not different between groups, even when regional inflation was accounted for.

Conclusions

During systemic endotoxemia, protective ventilation may reduce the magnitude and heterogeneity of pulmonary inflammatory cell metabolic activity in early lung injury and may improve gas exchange through its effects predominantly in dependent lung regions. Such effects are likely related to a reduction in the metabolic activity, but not in the number, of lung-infiltrating neutrophils.     

Effects of aspirin on the expression of nuclear factor-κB in a rat model of acute pulmonary embolism

BACKGROUND:

Acute pulmonary embolism (APE) is a disorder involving the pulmonary circulation resulting from a blockage of the pulmonary artery. The present study aimed to investigate the effects of aspirin on the nuclear factor-κB (NF-κB) activity in a rat model of APE.

METHODS:

A total of 108 healthy male Sprague-Dawley rats were randomly assigned into six groups (n=18 rats per group): control group, sham operation group, APE model group, and low-, medium- and high-dose aspirin groups. Six, 24, and 72 hours after the induction of APE, rats in the low-, medium- and high-dose aspirin groups were given aspirin at a respective daily dose of 150, 300, and 600 mg/kg by gavage for three consecutive days. Rats in the other groups were treated with equal volumes of normal saline. Six rats in each group were anesthetized with 10% chloral hydrate solution at each time point, and then the lung tissues were collected and analyzed using immunohistochemical staining.

RESULTS:

Positive immunohistochemical staining was present in the bronchial epithelial cells, alveolar cells, macrophages, and surrounding bronchial smooth muscle cells. When compared with the APE model group, the number of positive cells was significantly lower in the other groups at each time point (P<0.001). Statistically significant differences were also observed among the aspirin-treated groups at 6 hours (P<0.05, P<0.001). Compared with the APE model group, NF-κB protein expression was reduced in the other groups at each time point (P<0.05, P<0.001). Rats from the APE model group had thrombosis, damaged alveolar walls, and pulmonary hemorrhage, along with different degrees of inflammatory cellular infiltration at each time point. However, pathological changes such as pulmonary hemorrhage and infiltration of inflammatory cells were attenuated after the aspirin treatment.

CONCLUSION:

Aspirin can significantly inhibit NF-κB activity in the lung of rats with APE in a dose-dependent manner, and can alleviate lung injury after APE.KEY WORDS: Aspirin, Acute pulmonary embolism, Nuclear factor-κB     

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

BACKGROUND:

This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.

METHODS:

Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group (NS group), 6 rats; paraquat poisoning group (PQ group), 30 rats; and paraquat+lipoic acid treatment group (LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Whole blood (0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.

RESULTS:

HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup (P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals (P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals (P<0.01), but the differences between different intervals in the PQ group were statistically significant (P<0.05). The differences between different intervals in the LA group were statistically significant (P<0.01).

CONCLUSION:

Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.KEYWORDS: Lipoic acid, Paraquat, Acute lung injury, Surfactant protein, Tumor necrosis factor-α, Oxygen free radical, Superoxide dimutase, Malonaldehyde     

Effect of glucocorticoid on MIP-1α and NF-κB expressing in the lung of rats undergoing mechanical ventilation with a high tidal volume

BACKGROUND:

Ventilator induced lung injury (VILI) is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α (MIP-1α) in plasma and bronchoalveolar lavage fluid (BALF) and the expression of MIP-1α mRNA and nuclear factor-kappa B (NF-κB) p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.

METHODS:

Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury (VILI) group, a dexamethasone (DEX) group and a budesonide (BUD) group. The content of MIP-1α in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-κBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.

RESULTS:

The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-KBp65 mRNA in the lung in the DEX and BUD groups were significantly lower than those in the VILI group (P<0.001). Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-κBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no significant differences between them (P>0.05).

CONCLUSIONS:

Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-κB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.KEY WORDS: Mechanical ventilation, Lung injury, Macrophage inflammatory protein-1α, Nuclear factor-kappa B, Glucocorticoid, Inflammation     

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

BACKGROUND:

Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms.

METHODS:

Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa).

RESULTS:

TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05).

CONCLUSIONS:

There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.KEY WORDS: Hyperbaric oxygen, Ischemia-reperfusion injury, Apoptosis     

Effect of early goal directed therapy on tissue perfusion in patients with septic shock

BACKGROUND:

This study aimed to observe the effect of early goal directed therapy (EGDT) on tissue perfusion, microcirculation and tissue oxygenation in patients with septic shock.

METHODS:

Patients with early septic shock (<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled (research time: 12 months), and they didn’t meet the criteria of EGDT. Patients who had one of the following were excluded: stroke, brain injury, other types of shock, severe heart failure, acute myocardial infarction, age below 18 years, pregnancy, end-stage disease, cardiac arrest, extensive burns, oral bleeding, difficulty in opening the mouth, and the onset of septic shock beyond 24 hours. Patients treated with the standard protocol of EGDT were included. Transcutaneous pressure of oxygen and carbon dioxide (PtcO₂, PtcCO₂) were monitored and hemodynamic measurements were obtained. Side-stream dark field (SDF) imaging device was applied to obtain sublingual microcirculation. Hemodynamics, tissue oxygen, and sublingual microcirculation were compared before and after EGDT. If the variable meets the normal distribution, Student''s t test was applied. Otherwise, Wilcoxon''s rank-sum test was used. Correlation between variables was analyzed with Pearson''s product-moment correlation coefficient method.

RESULTS:

Twenty patients were involved, but one patient wasn’t analyzed because he didn’t meet the EGDT criteria. PtcO₂ and PtcCO₂ were monitored in 19 patients, of whom sublingual microcirculation was obtained. After EGDT, PtcO₂ increased from 62.7±24.0 mmHg to 78.0±30.9 mmHg (P<0.05) and tissue oxygenation index (PtcO₂/FiO₂) was 110.7±60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT (P<0.05). The difference between PtcCO₂ and PCO₂ decreased significantly after EGDT (P<0.05). The density of perfused small vessels (PPV) and microcirculatory flow index of small vessels (MFI) tended to increase, but there were no significant differences between them (P>0.05). PtcO₂, PtcO₂/FiO₂, and PtcCO₂ were not linearly related to central venous saturation, lactate, oxygen delivery, and oxygen consumption (P>0.05).

CONCLUSION:

Peripheral perfusion was improved after EGDT in patients with septic shock, and it was not exactly reflected by the index of systemic perfusion.KEY WORDS: Transcutaneous pressure of oxygen, Transcutaneous pressure of carbon dioxide, Microcirculation, Septic shock, EGDT, Tissue perfusion, Tissue oxygenation, Sidestream dark field imaging     

Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency

BACKGROUND:

This study aimed to investigate the risk factors and outcome of critically ill cancer patients with postoperative acute respiratory insufficiency.

METHODS:

The data of 190 critically ill cancer patients with postoperative acute respiratory insufficiency were retrospectively reviewed. The data of 321 patients with no acute respiratory insufficiency as controls were also collected. Clinical variables of the first 24 hours after admission to intensive care unit were collected, including age, sex, comorbid disease, type of surgery, admission type, presence of shock, presence of acute kidney injury, presence of acute lung injury/acute respiratory distress syndrome, acute physiologic and chronic health evaluation (APACHE II) score, sepsis-related organ failure assessment (SOFA), and PaO₂/FiO₂ ratio. Duration of mechanical ventilation, length of intensive care unit stay, intensive care unit death, length of hospitalization, hospital death and one-year survival were calculated.

RESULTS:

The incidence of acute respiratory insufficiency was 37.2% (190/321). Multivariate logistic analysis showed a history of chronic obstructive pulmonary diseases (P=0.001), surgery-related infection (P=0.004), hypo-volemic shock (P<0.001), and emergency surgery (P=0.018), were independent risk factors of postoperative acute respiratory insufficiency. Compared with the patients without acute respiratory insufficiency, the patients with acute respiratory insufficiency had a prolonged length of intensive care unit stay (P<0.001), a prolonged length of hospitalization (P=0.006), increased intensive care unit mortality (P=0.001), and hospital mortality (P<0.001). Septic shock was shown to be the only independent prognostic factor of intensive care unit death for the patients with acute respiratory insufficiency (P=0.029, RR: 8.522, 95%CI: 1.243–58.437, B=2.143, SE=0.982, Wald=4.758). Compared with the patients without acute respiratory insufficiency, those with acute respiratory insufficiency had a shortened one-year survival rate (78.7% vs. 97.1%, P<0.001).

CONCLUSION:

A history of chronic obstructive pulmonary diseases, surgery-related infection, hypovolemic shock and emergency surgery were risk factors of critically ill cancer patients with postoperative acute respiratory insufficiency. Septic shock was the only independent prognostic factor of intensive care unit death in patients with acute respiratory insufficiency. Compared with patients without acute respiratory insufficiency, those with acute respiratory insufficiency had adverse short-term outcome and a decreased one-year survival rate.KEY WORDS: Acute respiratory insufficiency, Risk factors, Prognosis, Critical illness, Postoperative care, Septic shock, Chronic obstructive pulmonary disease, Survival     

Imaging in detecting sites of pulmonary fibrosis induced by paraquat

BACKGROUND:

The most common cause of death from paraquat (PQ) poisoning is respiratory failure from pulmonary fibrosis, which develops through pathological overproduction of extracellular matrix proteins such as collagens. In this study, a MicroCT system was used to observe dynamic changes of pulmonary fibrosis in rats with PQ poisoning, and find the characteristics of interstitial lung diseases via density-based and texture-based analysis of CT images of the lung structure.

METHODS:

A total of 15 male SD rats were randomly divided into a control group (n=5) and a PQ poisoning group (n=10). The rats in the poisoning group were intraperitoneally administered with 4 mg/ mL PQ at 14 mg/kg, and the rats in the control group were administered with the same volume of saline. The signs of pulmonary fibrosis observed by the MicroCT included ground-glass opacity, nodular pattern, subpleural interstitial thickening, consolidation honeycomb-like shadow of the lung.

RESULTS:

Compared with the control group, the rats with acute PQ poisoning had different signs of pulmonary fibrosis. Ground-glass opacity and consolidation of the lung appeared at the early phase of pulmonary fibrosis, and subpleural interstitial thickening and honeycomb-like shadow developed at the middle or later stage. MicroCT images showed that fibrotic lung tissues were denser than normal lungs, and their density was up-regulated with pulmonary fibrosis. There was no difference in the progress of pulmonary fibrosis between the right lung and the left lung (P>0.05), but there were differences in fibrosis degree at different sites in the lung (P<0.05 or P<0.01). Pulmonary fibrosis was mainly seen in the exterior area of the middle-lower part of the lung.

CONCLUSION:

Imaging can show the development of pulmonary fibrosis in PQ poisoning rats, and this method may help to administer drugs more reasonably in treating pulmonary fibrosis.KEY WORDS: MicroCT, CT value, Paraquat, Pulmonary fibrosis, Region of interest     

Effects of early rehabilitation therapy on patients with mechanical ventilation

BACKGROUND:

For patients in intensive care unit (ICU), mechanical ventilation is an effective treatment to survive from acute illness and improve survival rates. However, long periods of bed rest and restricted physical activity can result in side effects. This study aimed to investigate the feasibility of early rehabilitation therapy in patients with mechanical ventilation.

METHODS:

A randomized controlled trial was carried out. Sixty patients, with tracheal intubation or tracheostomy more than 48 hours and less than 72 hours, were admitted to the ICU of the Affiliated Hospital of Medical College, Qingdao University, from May 2010 to May 2012. These patients were randomly divided into a rehabilitation group and a control group. In the rehabilitation group, rehabilitation therapy was performed twice daily, and the training time and intensity were adjusted according to the condition of the patients. Early rehabilitation therapy included heading up actively, transferring from the supine position to sitting position, sitting at the edge of the bed, sitting in chair, transferring from sitting to standing, and ambulating bedside. The patient''s body mass index, days to first out of bed, duration of mechanical ventilation, length of ICU stay, APACHE II score, highest FiO₂, lowest PaO₂/FiO₂ and hospital mortality of patients were all compared between the rehabilitation group and the control group. The differences between the two groups were compared using Student''s t test.

RESULTS:

There was no significant difference in body mass index, APACHE II score, highest FiO₂, lowest PaO₂/FiO₂ and hospital mortality between the rehabilitation group and the control group (P>0.05). Patients in the rehabilitation group had shorter days to first out of bed (3.8±1.2 d vs. 7.3±2.8 d; P=0.00), duration of mechanical ventilation (5.6±2.1 d vs. 12.7±4.1 d; P=0.005) and length of ICU stay (12.7±4.1 d vs. 15.2±4.5 d; P=0.01) compared with the control group.

CONCLUSION:

Early rehabilitation therapy was feasible and effective in improving the outcomes of patients with mechanical ventilation.KEYWORDS: Early rehabilitation therapy, Mechanical ventilation, Intensive care unit, Hospital mortality, APACHE II score     

The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

BACKGROUND:

Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as CD31, is mainly distributed in vascular endothelial cells. Studies have shown that PECAM-1 is a very significant indicator of angiogenesis, and has been used as an indicator for vascular endothelial cells. The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury (ALI) and fibrosis in paraquat (PQ) induced lung injury in rabbits.

METHODS:

Thirty-six adult New Zealand rabbits were randomly divided into three groups (12 rabbits in each group) according to PQ dosage: 8 mg/kg (group A), 16 mg/kg (group B), and 32 mg/kg (group C). After PQ infusion, the rabbits were monitored for 7 days and then euthanized. The lungs were removed for histological evaluation. Masson staining was used to determine the degree of lung fibrosis (LF), and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1. Pearson’s product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.

RESULTS:

Rabbits in the three groups showed apparent poisoning. The rabbits survived longer in group A than in groups B and C (6.47±0.99 days vs. 6.09±1.04 days vs. 4.77±2.04 days) (P<0.05). ALI score was lower in group A than in groups B and C (8.33±1.03 vs. 9.83±1.17 vs. 11.50±1.38) (P<0.05), and there was statistically significant difference between group B and group C (P=0.03). LF was slighter in group A than in groups B and C (31.09%±2.05 % vs. 34.37%±1.62 % vs. 36.54%±0.44%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.026). The PEACAM-1 expression was higher in group A than in groups B and C (20.31%±0.70% vs. 19.34%±0.68% vs. 18.37%±0.46%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.017). Pearson’s correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score (Coe=–0.732, P=0.001) and degree of LF (Coe=–0.779, P<0.001).

CONCLUSIONS:

The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning, and the decrease is dose-dependent. The PECAM-1 expression is negatively correlated with ALI score and LF, showing a significant role in the development of lung injuries induced by PQ.KEY WORDS: Platelet endothelial cell adhesion molecule-1, Paraquat, Acute lung injury, Lung fibrosis