Impact of Sevoflurane Versus Propofol Anesthesia on Post-Operative Cognitive Dysfunction in Elderly Cancer Patients: A Double-Blinded Randomized Controlled Trial.

BACKGROUND Research on the clinical outcomes of surgical patients anaesthetized with sevoflurane and the association of sevoflurane with post-operative cognitive dysfunction (POCD) is scarce. We evaluated whether sevoflurane-based anesthesia increased the incidence of POCD and worsened prognosis compared to propofol-based anesthesia in elderly cancer patients. MATERIAL AND METHODS This single-center, prospective, double-blind randomized controlled trial included 234 patients aged 65 to 86 years undergoing tumor resection who received sevoflurane-based (Group S) or propofol-based (Group P) anesthesia during surgery. A series of neuropsychological tests was performed to evaluate cognitive function before surgery and at 7 days and 3 months post-operation, and the results were compared to those of healthy controls. RESULTS At 7 days post-operation there were no significant differences in the incidence of POCD between patients who received sevoflurane-based or propofol-based anesthesia during surgery: Group S was at 29.1% (32 out of 110 patients) versus Group P at 27.3% (30 out of 110), P=0.764. At 3 months, Group S was at 11.3% (12 out of 106 patients) versus Group P at 9.2% (10 out of 109), P=0.604. During the first 2 days post-operation, the QoR-40 global score was significantly lower in Group S compared to Group P [POD 1: P=0.004; POD 2: P=0.001]. There were no significant differences in in-hospital post-operative complications, post-operative length of hospital stay, all-cause mortality at 30 days, and 3 months post-operation, or post-operative quality of life at 3 months between patients in Group S and Group P. CONCLUSIONS Sevoflurane-based anesthesia did not increase the incidence of POCD compared to propofol-based anesthesia at 7 days or 3 months post-operation or impact short-term post-operative prognosis.

A resorufin-based fluorescence probe for visualizing biogenic amines in cells and zebrafish.

Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 µM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance.

Neutrophil-Derived IL-17 Promotes Ventilator-Induced Lung Injury via p38 MAPK/MCP-1 Pathway Activation.

Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation and can severely affect health. VILI appears to involve excessive inflammatory responses, but its pathogenesis has not yet been clarified. Since interleukin-17 (IL-17) plays a critical role in the immune system and the development of infectious and inflammatory diseases, we investigated here whether it plays a role in VILI. In a mouse model of VILI, mechanical ventilation with high tidal volume promoted the accumulation of lung neutrophils, leading to increased IL-17 levels in the lung, which in turn upregulated macrophage chemoattractant protein-1 via p38 mitogen-activated protein kinase. Depletion of neutrophils decreases the production IL-17 in mice and inhibition of IL-17 significantly reduced HTV-induced lung injury and inflammatory response. These results were confirmed in vitro using RAW264.7 macrophage cultures. Our results suggest that IL-17 plays a pro-inflammatory role in VILI and could serve as a new target for its treatment.

Ly-6Chigh inflammatory-monocyte recruitment is regulated by p38 MAPK/MCP-1 activation and promotes ventilator-induced lung injury.

Lymphocyte antigen 6Chigh (Ly-6Chigh) inflammatory monocytes, as novel mononuclear cells in the innate immune system, participate in infectious diseases. In this study, we investigated the potential role of these monocytes in ventilator-induced lung injury (VILI) and the possible mechanism involved in their migration to lung tissue. Our results showed that mechanical ventilation with high tidal volume (HTV) increased the accumulation of Ly-6Chigh inflammatory monocytes in lung tissues and that blocking C­C chemokine receptor 2 (CCR2) could significantly reduce Ly-6Chigh inflammatory-monocyte migration and attenuate the degree of inflammation of lung tissues. In addition, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) activity could decrease the secretion of monocyte chemoattractant protein 1 (MCP-1), which in turn decreased the migration of Ly-6Chigh inflammatory monocytes into lung tissue. We also demonstrated that high ventilation caused Ly-6Chigh inflammatory monocytes in the bone marrow to migrate into and aggregate in the lungs, creating inflammation, and that the mechanism was quite different from that of infectious diseases. Ly-6Chigh inflammatory monocytes might play a pro-inflammatory role in VILI, and blocking their infiltration into lung tissue might become a new target for the treatment of this injury.

Clinical impact of type 2 diabetes mellitus on outcomes after one-lung ventilation during thoracic surgery: a retrospective cohort study.

BACKGROUND: The preoperative presence of diabetes mellitus (DM) has been recently demonstrated to be a risk factor for adverse events after thoracic surgery. However, the specific effects of presence of DM preoperatively on thoracic surgery is not known. This study aimed to investigate the association between preoperative DM and clinical outcomes and the short-term survival rates after thoracic surgery. METHODS: In this retrospective, observational, and matched-pair analysis study, patients receiving thoracic surgery from a tertiary university hospital in 2 consecutive years were grouped as either type 2 DM (T2DM) or controlled within the first 24 hours after surgery. Multivariate Cox regression was conducted to investigate the impact of T2DM within the first 24 hours of admission on in-intensive care unit (ICU) and hospital survival. RESULTS: Among the included thoracic patients, 41 (8.4%) had T2DM and 450 (91.6%) did not have T2DM. In the single-factor analyses, T2DM patients were shown to have a higher preoperative white blood cells (WBCs) count, increased release of immunoglobulin A, complement C3 and C4, impaired kidney function with high level of urea, and low expression of alanine aminotransferase (ALT) and monoamine oxidase (MAO). In multivariate analyses, the preoperative urea level was associated with a low-grade risk of dying for the ICU survival time. In contrast, preoperative complement C3 level favored a positive contribution in-ICU survival. Besides the complement C3 level, immunoglobulin A level remained a positive contribution in regression models of hospital survival. CONCLUSIONS: Pre-admission T2DM was not associated with an increased in-ICU and hospital mortality among patients with thoracic surgery. Furthermore, they were accompanied by impaired kidney function, activated inflammation and liver function.

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway.

BACKGROUND: In animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear. METHODS: A model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretching-induced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury. RESULTS: Using a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression. CONCLUSION: These findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism in which released mtDNA activates TLR9 and thereby the MyD88/NF-κB pathway. Inhibiting this process may be a therapeutic approach to prevent inflammation and cell injury in patients on mechanical ventilation.

Non-intubated anesthesia in patients undergoing video-assisted thoracoscopic surgery: A systematic review and meta-analysis.

INTRODUCTION: Non-intubated anesthesia (NIA) has been proposed for video-assisted thoracoscopic surgery (VATS), although how the benefit-to-risk of NIA compares to that of intubated general anesthesia (IGA) for certain types of patients remains unclear. Therefore, the aim of the present meta-analysis was to understand whether NIA or IGA may be more beneficial for patients undergoing VATS. METHODS: A systematic search of Cochrane Library, Pubmed and Embase databases from 1968 to April 2019 was performed using predefined criteria. Studies comparing the effects of NIA or IGA for adult VATS patients were considered. The primary outcome measure was hospital stay. Pooled data were meta-analyzed using a random-effects model to determine the standard mean difference (SMD) with 95% confidence intervals (CI). RESULTS AND DISCUSSION: Twenty-eight studies with 2929 patients were included. The median age of participants was 56.8 years (range 21.9-76.4) and 1802 (61.5%) were male. Compared to IGA, NIA was associated with shorter hospital stay (SMD -0.57 days, 95%CI -0.78 to -0.36), lower estimated cost for hospitalization (SMD -2.83 US, 95% CI -4.33 to -1.34), shorter chest tube duration (SMD -0.32 days, 95% CI -0.47 to -0.17), and shorter postoperative fasting time (SMD, -2.76 days; 95% CI -2.98 to -2.54). NIA patients showed higher levels of total lymphocytes and natural killer cells and higher T helper/T suppressor cell ratio, but lower levels of interleukin (IL)-6, IL-8 and C-reactive protein (CRP). Moreover, NIA patients showed lower levels of fibrinogen, cortisol, procalcitonin and epinephrine. CONCLUSIONS: NIA enhances the recovery from VATS through attenuation of stress and inflammatory responses and stimulation of cellular immune function.

Conscious Sedation versus General Anesthesia for Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-Analysis.

The aim of this study is to compare the effect of conscious sedation (CS) with general anesthesia (GA) on clinical outcomes in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT). MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017) were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ≦ 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ≦ 2 at hospital discharge and one or three months was increased.

High Tidal Volume Induces Mitochondria Damage and Releases Mitochondrial DNA to Aggravate the Ventilator-Induced Lung Injury.

OBJECTIVE: This study aimed to determine whether high tidal volume (HTV) induce mitochondria damage and mitophagy, contributing to the release of mitochondrial DNA (mtDNA). Another aim of the present study was to investigate the role and mechanism of mtDNA in ventilator-induced lung injury (VILI) in rats. METHODS: Rats were tracheotomized and allowed to breathe spontaneously or mechanically ventilated for 4 h. After that, lung injury was assessed. Inhibition of toll-like receptor 9 (TLR9), named ODN2088, was used to determine the involvement of TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in VILI. The mitochondrial damage and release of mtDNA were assessed. Pharmacological inhibition of mtDNA (chloroquine) was used to determine whether mtDNA trigger inflammation via TLR9 in VILI. EDU-labeled mtDNA deriving from mitophagy was assessed by immunofluorescence. The role of mitophagy in VILI was shown by administration of antimycin A and cyclosporine A. MAIN RESULTS: Rats subjected to HTV showed more severe pulmonary edema and inflammation than the other rats. The decreased expression of TLR9, MyD88, and NF-κB were observed following the use of ODN2088. Mechanical ventilation (MV) with HTV damaged mitochondria which resulted in dysfunctional ATP synthesis, accumulation of reactive oxygen species, and loss of mitochondrial membrane potential. Moreover, the results of distribution of fluorescence in rats upon HTV stimulation indicated that mtDNA cleavage was associated with mitophagy. The expression levels of mitophagy related genes (LC3B-II/LC3B-I, PINK1, Parkin, and mitofusin 1) in animals ventilated with HTV were significantly upregulated. Administration of antimycin A aggregated the histological changes and inflammation after MV, but these effects were attenuated when administered in the presence of cyclosporine A. CONCLUSION: MV with HTV induces mitochondrial damage and mitophagy, contributing to the release of mtDNA, which may be induced VILI in rat via TLR9/MyD88/NF-κB signaling pathway.

[Study on Rac1/MAPK/ERK pathway mediated mechanism and role in rats with ventilator induced lung injury].

OBJECTIVE: To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism. METHODS: Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group, normal tidal volume (VT) group and high VT group with 10 rats in each group. The rats in spontaneous respiration group were kept their spontaneous breathing. The rats in normal VT group and high VT group were performed tracheal intubation after tracheostomy, and underwent mechanical ventilation on bilateral lungs with 6 mL/kg and 40 mL/kg VT respectively with maintenance anesthesia. After 4-hour ventilation, heart blood, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The levels of interleukins (IL-1ß, IL-6), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA). Lung wet/dry radio (W/D) was determined. The lung tissues were stained with hematoxylin and eosin (HE), and pathological changes were observed, and pathological scores were evaluated. The ultra structure changes in type II alveolar epithelial cells (AEC II) were observed with transmission electron microscope. The positive expressions of phosphorylation of extracellular signal-regulated kinase (p-ERK) were determined by immunohistochemistry, and those of Rac1 and F-actin were determined by immunofluorescence. The mRNA expressions of ERK and Rac1 were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR), and protein expressions of Rac-1, p-ERK and F-actin were determined by Western Blot. RESULTS: (1) Compared with spontaneous breathing group, lung W/D in both mechanical ventilation groups was significantly increased, with more significant increase in the high VT group (6.64±0.88 vs. 1.79±0.36, P < 0.01). (2) There was no obvious pathological changes in the lung tissue and AEC II of the spontaneously breathing group. In the normal VT group, there was slight edema and infiltration of inflammatory cells; AEC II had less lamellar bodies and uniform distribution of the villi of the alveolar epithelium. In the high VT group, the edema of the lung tissue, the widening of the pulmonary septum, the alveolus congestion, the infiltration of inflammatory cells, and alveolar structure disorder were found; and AEC II was irregular, the number of lamellar bodies in the plastids was decreased and was unevenly distributed. The pulmonary histopathological score in the high VT group was significantly higher than that in the spontaneous breathing group and the normal VT group (12.00±2.00 vs. 6.00±1.51, 8.50±0.53, both P < 0.01). (3) Compared with spontaneous breathing group, IL-1ß, IL-6, TNF-α, MPO, and MIP-2 in serum and BALF in both mechanical ventilation groups were significantly increased, with more significant increase in the high VT group [serum IL-1ß (ng/L): 104.2±15.1 vs. 20.3±8.3, IL-6 (ng/L): 46.6±11.5 vs. 22.7±7.5, TNF-α (ng/L): 39.4±6.5 vs. 5.4±1.9, MPO (ng/L): 0.66±0.24 vs. 0.06±0.03, MIP-2 (ng/L): 109.2±25.8 vs. 22.8±8.4; BALF IL-1ß (ng/L): 121.5±25.6 vs. 24.0±7.5, IL-6 (ng/L): 136.7±32.7 vs. 31.4±10.5, TNF-α (ng/L): 98.0±14.8 vs. 10.1±2.6, MPO (ng/L): 0.80±0.31 vs. 0.08±0.04, MIP-2 (ng/L): 144.4±28.9 vs. 41.2±20.7; all P < 0.01]. (4) There were only a few p-ERK, Rac1 and F-actin positive expressions in the spontaneous breathing group. The positive expressions in normal VT group were increased. In high VT group, the positive expression of p-ERK was significantly increased; Rac1 and F-actin were mainly distributed in the cell membrane and cytoplasm respectively, the positive expressions were further enhanced. (5) The gene expressions of ERK and Rac1, and protein expressions of p-ERK, Rac1 and F-actin in the high VT group were significantly higher than those in the spontaneous breathing group and normal VT group [ERK mRNA (2-ΔΔCt): 8.23±2.83 vs. 1, 3.02±1.38, p-ERK protein (gray value): 1.15±0.36 vs. 0.61±0.23, 0.88±0.22; Rac1 mRNA (2-ΔΔCt): 4.45±2.26 vs. 1, 1.22±0.39, Rac1 protein (gray value): 0.91±0.16 vs. 0.48±0.11, 0.55±0.10; F-actin protein (gray value): 0.70±0.09 vs. 0.49±0.08, 0.55±0.04; all P < 0.01]. CONCLUSIONS: F-actin expression in lung tissue was up-regulated in rats with VILI, which resulted in reconstruction of AEC II cyto-skeleton, and variation of cell membrane permeability through Rac1/MAPK/ERK signaling pathway during VILI.

Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model.

OBJECTIVE: To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator-induced lung injury (VILI). METHODS: Male, adult pathogen-free Sprague-Dawley rats weighing 300-350 g were used in this study. Animals were tracheotomized and allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF-κΒ of alveolar macrophages' expression under the different ventilation conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL-1ß were assessed as well. RESULTS: Rats subjected to high tidal volume showed significantly greater pulmonary permeability and lung inflammatory than the control rats. Alveolar macrophages from rats subjected to high tidal volume also showed significantly higher protein expression of TLR2 (0.59±0.049 vs. 0.35±0.036 and 0.36±0.031, both P<0.001), TLR4 (0.845±0.0395 vs. 0.401±0.026 and 0.403±0.020, both P<0.001), TLR9 (0.727±0.074 vs. 0.383±0.039 and 0.367±0.043, both P<0.001), MyD-88 (1.01±0.060 vs. 0.485±0.045 and 0.507±0.046, both P<0.001) and NF-κΒ (0.776±0.067 vs. 0.448±0.043 and 0.481±0.047, both P<0.001), as well as significantly higher concentrations of IL-6 (7.32±0.24 vs. 2.42±0.13 and 2.44±0.32, both P<0.001) and IL-1ß (139.95±9.37 vs. 53.63±5.26 and 53.55±6.63, both P<0.001) than the control and low tidal volume group. CONCLUSIONS: The overexpression of TLR2, TLR4, and TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a role in VILI.

Comparison of three ventilatory modes during one-lung ventilation in elderly patients.

OBJECTIVE: The purpose of this study was to explore the effects of three different ventilatory modes: volume controlled ventilation (VCV), pressure controlled ventilation (PCV) and pressure controlled ventilation-volume guaranteed (PCV-VG) on arterial oxygenation and airway pressure during one-lung ventilation (OLV) in elderly patients. METHODS: We enrolled 66 patients who underwent thoracic surgery requiring at least 1 hour of OLV and aged above 65 years into the study. Patients were classified into VCV, PCV and PCV-VG groups according to a controlled, randomized design. Patients were ventilated to obtain a tidal volume (TV) of 8 mL/kg with three different ventilatory modes during OLV. The Hemodynamic and respiratory data had been recorded during intraoperation and arterial blood gases were obtained at baseline, 20, 40, 60 minutes after OLV, end of surgery. RESULTS: Compared with VCV group, Ppeak was significantly lower in PCV and PCV-VG group (P<0.05), and the difference was not found between the PCV and PCV-VG group. PaO2 in PCV and PCV-VG group were higher than VCV group after the point of OLV+40 (P<0.05). Comparison of PCV group, PaO2 in PCV-VG group was higher, but did not show a significantly improved during OLV (P>0.05). CONCLUSIONS: Compared with VCV, the use of PCV and PCV-VG have a significant advantage in intraoperative oxygenation and airway pressure for eldly patients undergoing OLV.

Differential expression of HIF-1α, AQP-1, and VEGF under acute hypoxic conditions in the non-ventilated lung of a one-lung ventilation rat model.

AIMS: One-lung ventilation (OLV) is a standard practice in thoracic surgery. However, OLV can give rise to arterial hypoxemia. Hypoxia-inducible transcription factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF) and aquaporin-1 (AQP-1) may be involved in arterial hypoxemia and contribute to cellular injury. Therefore, in the present study, these moieties were investigated in an OLV rat model. MAIN METHODS: Forty Sprague-Dawley (S-D) rats were randomly divided into four groups: right lung mechanical ventilation for 0.5 h (Group A); 1 h (Group B); 2 h (Group C) and mechanical ventilation of both lungs (control group). Rat lung tissue was examined using electron microscopy. Serum and lung tissue levels of VEGF were measured by ELISA, Western blot analyses were used to detect the protein expression of HIF-1α and immunohistochemical staining and real-time polymerase chain reaction (PCR) were performed to examine protein expression and gene levels, respectively, of VEGF and AQP-1 after hypoxia. KEY FINDINGS: Electron microscopy revealed that increased duration of OLV was correlated with greater destruction of the non-ventilated lung. The protein expression of HIF-1α was significantly increased in the non-ventilated lungs of the experimental hypoxia groups (A-C) compared to the control group, whereas VEGF and AQP-1 protein expression and gene levels were decreased in the non-ventilated lungs of the hypoxia groups (A-C) compared to the control group. SIGNIFICANCE: The OLV caused hypoxia in the non-ventilated lung and subsequent injury. The altered expression of HIF-1α, VEGF, and AQP-1 may be involved in the pathological process of lung injury caused by hypoxia.

Pressure-controlled versus volume-controlled ventilation during one-lung ventilation in elderly patients with poor pulmonary function.

OBJECTIVE: THE AIM WAS TO INVESTIGATE THE EFFECTS OF TWO DIFFERENT VENTILATORY STRATEGIES: Pressure-controlled ventilation (PCV) versus volume-controlled ventilation (VCV) in elderly patients with poor pulmonary function during one-lung ventilation (OLV). PATIENTS AND METHODS: The patients were enrolled into the study having poor pulmonary function (forced expiratory volume in 1 s <1.5 L) and undergoing radical resection of pulmonary carcinoma requiring at least 2 h of OLV. Patients were respectively allocated to VCV group and PCV group. The intraoperative data, arterial, and mixed venous blood gases were obtained at baseline, 20, 40, 60, 80, 100 and 120 min after OLV and end of surgery. The postoperative data had been recorded and arterial gas measurements were performed at 6, 12 and 24 h after surgery in Intensive Care Unit. RESULTS: Comparison of the VCV group and PCV group, PaO2 and P(A-a)O2 were higher and dead space to tidal volume was lower in the PCV group (P < 0.05) after the point of OLV +60, Ppeak was higher in the VCV group (P < 0.05). There were significant advantages in PCV groups with regard to the PaO2 of three points in postoperation, the duration of postoperative ventilation duration, intensive care duration of stay and the days stay in hospital after surgery. CONCLUSIONS: The use of PCV compared with VCV during OLV in elderly patients with poor pulmonary function has significant advantages of intraoperative and postoperative oxygenation and it might be a factor, which can beneficial to postoperative recovery.

[The impacts of regulating Toll-like receptor 2/nuclear factor-ΚB signal pathway on rats with ventilator-induced lung injury].

OBJECTIVE: To evaluate the role of Toll-like receptor 2/nuclear factor-ΚB (TLR2/NF-ΚB) signaling pathway pretreatment in ventilator-induced lung injury (VILI). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into three groups by using random number scale, with 10 rats in each group. Group A: rats were given 200 µL of TLR2 monoclonal antibodies (TLR2mAb, 10 µg/kg) by slow instillation through tracheal catheter, and then ventilated with a high tidal volume (VT) of 40 mL/kg. Group B: ventilated with a normal VT of 8 mL/kg. Group C: rats were tracheally instilled with 10 µg/kg of TLR2mAb devoid of biologic activity, and then ventilated with a high VT of 40 mL/kg. The rats were mechanically ventilated for 4 hours, the lung wet to dry weight ratio (W/D) was calculated. The changes in pathology and ultrastructure in lung tissue were observed with microscope. Enzyme linked immunosorbent assay (ELISA) was performed to determine the concentration of interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) in serum and brconchoalveolar lavage fluid (BALF). Real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the mRNA expressions of TLR2, NF-ΚB and myeloid differentiation factor 88 (MyD88) in lung tissue. RESULTS: No obvious pathological changes in lungs were found in group A and group B, and no obvious damages to ultra-microstructure were found in lung macrophages, typeI epithelial cell and typeII epithelial cell. In group C, pathological changes were observed, including pulmonary alveoli fusion, alveoli septum thickening, inflammatory cells infiltration, and damages to ultrastructure of lung macrophage, damage to cell membrane of typeI epithelial cells and type II epithelial cells, vacuoles in cytoplasm, damage to organelle, and even pyknosis and perinuclear cistern thickening. Compared with group C, W/D ratio and mean concentration of inflammatory cytokines in serum and BALF showed a significant decrease in group A and B [W/D ratio: 1.151 ± 0.026, 1.128 ± 0.048 vs. 1.403 ± 0.062; concentration of IL-1ß in serum (ng/L): 37.05 ± 5.61, 34.52 ± 4.31 vs. 51.45 ± 8.18; concentration of IL-6 in serum (ng/L): 53.65 ± 5.16, 55.77 ± 5.62 vs. 89.96 ± 7.08; concentration of TNF-α in serum (ng/L): 71.93 ± 13.29, 67.36 ± 11.42 vs. 96.20 ± 11.60; concentration of IL-1ß in BALF (ng/L): 56.48 ± 6.16, 54.44 ± 7.26 vs. 99.77 ± 8.41; concentration of IL-6 in BALF (ng/L): 172.44 ± 21.26, 163.47±18.70 vs. 216.22 ± 23.90; concentration of TNF-α in BALF (ng/L): 235.81 ± 42.75, 231.72 ± 40.38 vs. 374.85 ± 69.61, all P<0.01], but there were no significant differences between group A and group B (all P>0.05). The mRNA expressions of TLR2, MyD88, and NF-ΚB were significantly decreased in group A and group B compared with those in group C [TLR2 mRNA(2(-Δ ΔCt)):1.021 ± 0.287, 0.938 ± 0.196 vs. 3.862 ± 0.871; MyD88 mRNA(2(-Δ ΔCt)):1.235 ± 0.277, 1.300 ± 0.306 vs. 3.618 ± 1.107; NF-ΚB mRNA(2(-Δ ΔCt)):0.519 ± 0.036, 1.043 ± 0.170 vs. 20.280 ± 9.466, P<0.05 or P<0.01], but there was no significant difference among the parameters mentioned above between group A and B (all P>0.05). CONCLUSIONS: To some extent, pre-intervention with TLR2mAb to block the TLR2/NF-ΚB signal pathway can inhibit the release of pro-inflammatory factors, and regulate the VILI.

[Role and mechanism of signal pathway mediated by Toll-like receptor 9-myeloid differentiation factor 88 in alveolar macrophages in ventilator-induced lung injury in rats].

OBJECTIVE: To investigate the role of Toll-like receptor 9 (TLR9)-myeloid differentiation factor 88 (MyD88) signal pathway in alveolar macrophages in ventilator-induced lung injury (VILI). METHODS: 30 adult male Sprague-Dawley (SD) rats were randomly assigned to three groups (with 10 rats in each group). Group A was the control group, with spontaneous respiration after tracheostomy. Rats in group B received mechanical ventilation for 4 hours with normal tidal volume (VT) 7 ml/kg after tracheostomy, and group C rats received mechanical ventilation with VT 40 ml/kg for 4 hours. After termination of ventilation, examination with transmission electron microscopy was performed to observe the ultrastructure changes in alveolar epithelial cell type II (AECII) of the lung. Lung wet/dry ratios (W/D) and total protein concentration, the concentration of interleukins (IL-6 and IL-1ß) in bronchoalveolar lavage fluid (BALF) were determined. The protein and mRNA expressions of TLR9, MyD88 and nuclear factor-ΚB (NF-ΚB) in alveolar macrophages were assayed by Western Blot and real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The ultrastructure of AECII in the group A and group B was almost normal, whereas the chromatin of the nuclei, the lamellar corpuscles in the cytoplasm, the cell membrane and the microvilli of the AECII in the group C showed injurious changes in various degrees. When the group C was compared with the group A and the group B, it was shown that the W/D ratios (5.54±0.17 vs. 4.58±0.17, 4.69±0.16) and total protein concentration (6.33±0.61 g/L vs. 0.45±0.05 g/L, 0.47±0.04 g/L), IL-6 (1.989±0.103 µg/L vs. 1.033±0.061 µg/L, 1.010±0.069 µg/L) and IL-1ß (2.79±0.25 ng/L vs. 1.05±0.15 ng/L, 1.23±0.22 ng/L) in BALF, the protein expressions of TLR9, MyD88 and NF-ΚB [TLR9 (A value): 0.770±0.042 vs. 0.300±0.027, 0.310±0.037; MyD88 (A value): 0.950±0.091 vs. 0.560±0.082, 0.580±0.084; NF-ΚB(A value): 1.020±0.076 vs. 0.740±0.052, 0.700±0.076] in alveolar macrophages were all increased significantly, and all of which showed significant difference (P<0.05 or P<0.01). The mRNA levels of TLR9, MyD88 and NF-ΚB in alveolar macrophages in the group B were (1.13±0.32), (1.18±0.33), and (1.11±0.22) folds of those of the group A, respectively, but there were no significant differences (all P>0.05). While the mRNA levels of TLR9, MyD88 and NF-ΚB of alveolar macrophages in the group C were (8.66±0.69), (6.41±0.53) and (5.29±0.71) folds of those of the group A, respectively, and all of them showed significant difference (all P<0.01). CONCLUSIONS: TLR9-MyD88 signaling in alveolar macrophages plays a role in pathogenesis of VILI.