The association of a frailty index derived from laboratory tests and vital signs with clinical outcomes in critical care patients with septic shock: a retrospective study based on the MIMIC-IV database.

PURPOSE: Frailty is a vulnerable state to stressors due to the loss of physiological reserve as a result of multisystem dysfunction. The physiological and laboratory-based frailty index (FI-Lab), depending on laboratory values and vital signs, is a powerful tool to capture frailty status. The aim of this study was to assess the relationship between FI-Lab and in-hospital mortality in patients with septic shock. METHODS: Baseline data for patients with sepsis in the intensive care unit were retrieved from the Critical Care Medicine Database (MIMIC-IV, v2.2). The primary outcome was mortality during hospitalization. The propensity score matching (PSM) method was used to analyze the basic conditions during hospitalization between groups.The FI-Lab was analysed for its relationship with in-hospital mortality using logistic regression according to continuous and categorical variables, respectively, and described using the restricted cubic spline (RCS). Survival was compared between groups using Kaplan-Meier (KM) curves. Subgroup analyses were used to improve the stability of the results. RESULTS: A total of 9219 patients were included. A cohort score of 1803 matched patients was generated after PSM. The analyses showed that non-surviving patients with septic shock in the ICU had a high FI-Lab index (P<0.001). FI-Lab, whether used as a continuous or categorical variable, increased with increasing FI-Lab and increased in-hospital mortality (P<0.001).Subgroup analyses showed similar results. RCS depicts this non-linear relationship. KM analysis shows the cumulative survival time during hospitalisation was significantly lower as FI-Lab increased (log-rank test, P<0.001). CONCLUSION: Elevated FI-Lab is associated with increased in-hospital mortality in patients with septic shock.

miR-132-3p promotes heat stimulation-induced esophageal squamous cell carcinoma tumorigenesis by targeting KCNK2.

Epidemiological evidence supports that consumption of high-temperature food and beverages is an important risk factor for esophageal squamous cell carcinoma (ESCC); however, the underlying mechanism still remains unclear. Here, we established a series of animal models and found that drinking 65°C water can promote esophageal tumor progression from preneoplastic lesions to ESCC. RNA sequencing data showed that miR-132-3p was highly expressed in the heat stimulation group compared with controls. Further study verified that miR-132-3p were upregulated in human premalignant lesion tissues of the esophagus, ESCC tissues, and cells. Overexpression of miR-132-3p could promote ESCC cell proliferation and colony formation, whereas knockdown of miR-132-3p could inhibit ESCC progression in vitro and in vivo. Importantly, dual-luciferase reporter assays showed that miR-132-3p could bind with the 3'-untranslated region of KCNK2 and inhibit KCNK2 gene expression. Knockdown or overexpression of KCNK2 could promote or suppress ESCC progression in vitro. These data suggest that heat stimulation can promote ESCC progression and miR-132-3p mediated this process by directly targeting KCNK2.

4D line-scan hyperspectral imaging.

This paper proposes a 4D line-scan hyperspectral imager that combines 3D geometrical measurement and spectral detection with high spectral resolution and spatial accuracy. We investigated the geometrical optical model of a camera attaching with a spectrograph, theoretically explored the mathematical model for line-scan fringe projection profilometry, and established the 3D reconstruction and calibration methods under this proposed line-scan high-dimensional imaging system. The spectral resolution of the system is 2.8 nm, and the spatial root-mean-square-error is 0.0895 mm when measuring a standard sphere with a diameter of 40.234 mm. We measure a colored statue to showcase the intensity change along the dimension of wavelength. In addition, the quality and defect of the spinach leaves are inspected based on spectral data and depth data, which demonstrates the potential application of the system in the food industry.

p21-activated kinase 4 promotes the progression of esophageal squamous cell carcinoma by targeting LASP1.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage-independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull-down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC.

Effects of Shen-Fu injection on mitochondrial function in the intestinal epithelial cells of rats with endotoxemia.

Recently, several studies have demonstrated that reactive oxygen species are responsible for inducing multiple organ failure and septic shock. Particularly, mitochondrial dysfunction has been demonstrated in the pathogenesis of multiple organ dysfunction syndrome (MODS). In cytopathic hypoxia, impairment of mitochondrial oxidative phosphorylation decreases aerobic adenosine triphosphate (ATP) production and potentially induces MODS. Shen-Fu (SF) injections are widely used in the treatment of various diseases. SF exhibits cardiovascular protective effects. For example, it can stretch the coronary artery, stabilize blood pressure, regulate IRI, and improve the overall heart function. Clinical studies have demonstrated that SF injections have notable therapeutic effects on septic and hemorrhagic shocks. In the present study, the effects of SF injection on mitochondrial function in the intestinal epithelial cells of rats with endotoxemia were analyzed.

T cell-mediated tumor killing based signature to predict the prognosis and immunotherapy for glioblastoma.

Despite the significant advancements in cancer treatment brought by immune checkpoint inhibitors (ICIs), their effectiveness in treating glioblastoma (GBM) remains highly dissatisfactory. Immunotherapy relies on the fundamental concept of T cell-mediated tumor killing (TTK). Nevertheless, additional investigation is required to explore its potential in prognostic prediction and regulation of tumor microenvironment (TME) in GBM. TTK sensitivity related genes (referred to as GSTTKs) were obtained from the TISIDB. The training cohort was available from the TCGA-GBM, while the independent validation group was gathered from GEO database. Firstly, we examined differentially expressed GSTTKs (DEGs) with limma package. Afterwards, the prognostic DEGs were identified and the TTK signature was established with univariate and LASSO Cox analyses. Next, we examined the correlation between the TTK signature and outcome of GBM as well as immune phenotypes of TME. Furthermore, the evaluation of TTK signature in predicting the effectiveness of immunotherapy has also been conducted. We successfully developed a TTK signature with an independent predictive value. Patients who had a high score experienced a worse prognosis compared to patients with low scores. The TTK signature showed a strong positive association with the infiltration degree of immunocyte and the presence of various immune checkpoints. Moreover, individuals with a lower score exhibited increased responsiveness to ICIs and experienced improved prognosis. In conclusions, we successfully developed and verified a TTK signature that has the ability to predict the outcome and immune characteristics of GBM. Furthermore, the TTK signature has the potential to direct the personalized immunotherapy for GBM.

TGF-ß based risk model to predict the prognosis and immune features in glioblastoma.

Background: Transforming growth factor-ß (TGF-ß) is a multifunctional cytokine with an important role in tissue development and tumorigenesis. TGF-ß can inhibit the function of many immune cells, prevent T cells from penetrating into the tumor center, so that the tumor cells escape from immune surveillance and lead to low sensitivity to immunotherapy. However, its potential roles in predicting clinical prognosis and tumor microenvironment (TME) immune features need to be deeply investigated in glioblastoma (GBM). Methods: The TCGA-GBM dataset was obtained from the Cancer Genome Atlas, and the validation dataset was downloaded from Gene Expression Omnibus. Firstly, differentially expressed TGF-ß genes (DEGs) were screened between GBM and normal samples. Then, univariate and multivariate Cox analyses were used to identify prognostic genes and develop the TGF-ß risk model. Subsequently, the roles of TGF-ß risk score in predicting clinical prognosis and immune characteristics were investigated. Results: The TGF-ß risk score signature with an independent prognostic value was successfully developed. The TGF-ß risk score was positively correlated with the infiltration levels of tumor-infiltrating immune cells, and the activities of anticancer immunity steps. In addition, the TGF-ß risk score was positively related to the expression of immune checkpoints. Besides, the high score indicated higher sensitivity to immune checkpoint inhibitors. Conclusions: We first developed and validated a TGF-ß risk signature that could predict the clinical prognosis and TME immune features for GBM. In addition, the TGF-ß signature could guide a more personalized therapeutic approach for GBM.

miRNA-130a-3p/CPEB4 Axis Modulates Glioblastoma Growth and Progression.

Glioblastoma is the most frequent form of malignant brain tumor. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is overexpressed and involved in the tumorigenesis and metastasis of glioblastoma. miR-130a-3p has been revealed to be aberrantly expressed in tumors and has aroused wide attention. In present study, we would like to investigate the effect and potential mechanism of miR-130a-3p on the proliferation and migration in glioblastoma. The relative expression levels of miR-130a-3p and CPEB4 in glioblastoma cell lines were detected by real-time quantitative polymerase chain reaction. Cell viability and migration were detected by methylthiazolyl tetrazolium assay and transwell assay, and cell cycle analysis was detected by flow cytometry. The expression of CPEB4 protein and epithelial-mesenchymal transition associated markers were detected by western blot. Bioinformatics and luciferase activity analysis were used to verify the targeting relationship between miR-130a-3p and CPEB4. We observed that the expression of CPEB4 was upregulated while that of miR-130a-3p was downregulated in glioblastoma cell lines. CPEB4 was validated as a target of miR-130a-3p by luciferase activity assay. Increased levels of miR-130a-3p inhibited the proliferation and migration of the glioblastoma cells and the overexpression of miR-130a-3p inhibited epithelial-mesenchymal transition. However, CPEB4 overexpression resisted the inhibitory effects of miR-130a-3p. Our study elucidates CPEB4 is upregulated because of the downregulated miR-130a-3p in glioblastoma, which enhances the glioblastoma growth and migration, suggesting a potential therapeutic target for the disease.

TCAF2 is associated with the immune microenvironment, promotes pathogenesis, and impairs prognosis in glioma.

PURPOSE: Glioma is the most common primary intracranial tumor and exhibits rapid growth and aggressiveness. TRPM8 channel-associated factor 2 (TCAF2), located in cell junctions and the plasma membrane, plays a key role in the pathogeneses of several cancers in humans. However, the role of TCAF2 in glioma has been elusive. METHODS: A combination of bioinformatic analysis using The Cancer Genome Atlas database and biological experiments, including 5-ethynyl-2'-deoxyuridine, transwell, and immunohistochemistry assays and xenotransplantation, was performed to analyze the expression level of TCAF2 and to mechanistically explore the relationship of TCAF2 with malignancy, prognosis, and the immune microenvironment in glioma. RESULTS: TCAF2 was upregulated in glioma, and its expression level correlated with tumor grade and clinical outcome. The role of TCAF2 in promoting glioma malignancy was characterized through in vitro and in vivo experiments. Additionally, we observed that TCAF2 can modulate the metabolic pathways and immune microenvironment. CONCLUSION: TCAF2 acts as an oncogene and may serve as a therapeutic target and prognostic marker in glioma.

Long non-coding RNA growth arrest specific 5 is downregulated in sepsis-ALI and inhibits apoptosis by up-regulating miR-146a.

Long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) and microRNA (miR)-146a both have inhibitory effects on LPS-induced inflammation, suggesting the crosstalk between them. In this study, the expression of GAS5 and miR-146a in patients with sepsis-induced acute lung injury (sepsis-ALI), sepsis patients without obvious complications (sepsis) and healthy controls were studied by RT-qPCR. The role of GAS5 in the expression and methylation of miR-146a in human bronchial epithelial cells (HBEpCs) were studied by RT-qPCR and methylation-specific PCR (MSP), respectively. Cell apoptosis was analyzed by flow cytometry. We found that GAS5 and miR-146a were downregulated in sepsis-ALI and the expression of these two were correlated. LPS induced the downregulation of GAS5 and miR-146a in HBEpCs. In HBEpCs, overexpression of GAS5 increased the expression levels of miR-146a and reduced the methylation of miR-146a gene. Under lipopolysaccharide (LPS) treatment, overexpression of GAS5 and miR-146a decreased the apoptotic rate of HBEpCs. Moreover, the combined overexpression of GAS5 and miR-146a showed stronger effects. Therefore, GAS5 is downregulated in sepsis-ALI and inhibits cell apoptosis by up-regulating the expression of miR-146a.

Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.

PURPOSE: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure. METHODS: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality. RESULTS: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies. CONCLUSIONS: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

[Effects of combination of midazolam and propofol on anterograde amnesia in critical patients].

OBJECTIVE: To observe the effects of sedation with midazolam and propofol on anterograde amnesia in critical patients. METHODS: Sixty selected patients on mechanical ventilation in intensive care unit (ICU) were randomly divided into three subgroups (propofol, midazolam, and midazolam and propofol combination group), with 20 cases in each group. Patients who were awakened from sedation were showed with a card depicted with different colors, figures and numbers. When patients were totally conscious after weaning from mechanical ventilation,the influence of the different methods of sedation on anterograde amnesia of these critically ill patients was assessed. RESULTS: (1) 70%, 95% and 90% of patients manifested amnesia in propofol, midazolam and the combination group, respectively. All the patients recovered their memory immediately in 30 minutes after withdrawal of the sedatives. (2) When midazolam was compared with propofol and combination group, time of onset was obviously prolonged after an intravenous injection of a load dose in midazolam group [(2.7+/-1.1) minutes and (3.1+/-1.3) minutes vs. (5.1+/-2.8) minutes], also was time of extubation after regaining of consciousness [(0.7+/-0.2) hour and (1.2+/-0.6) hours vs. (2.7+/-0.3) hours, all P<0.01]. There was no significant difference between propofol group and the combination group in time of onset and extubation (both P>0.05). (3) Cost of propofol [(2,100+/-125) yuan] was 75% higher than that of midazolam [(1,200+/-112) yuan, P<0.01], but cost of sedatives in the combination group [(1,300+/-132) yuan] was similar to that in midazolam group (P>0.05). CONCLUSION: Combination of midazolam and propofol can not only ensure anterograde amnesia in critical patients, reduce drug dosage and adverse reactions, but also can help reduce the hospital expenses. This method may be a better sedation program in ICU.

[Effect of recruitment maneuver on alveolar epithelium barrier in rat with acute lung injury].

OBJECTIVE: To evaluate the influence of recruitment maneuver (RM) on alveolar epithelium barrier in rat with acute lung injury (ALI). METHODS: The ALI rats model were replicated by lipopolysaccharide iv injection. Sustained inflation (SI), as a method of RM, was applied by airway pressure of 30 cm H(2)O for 30 seconds. Forty-eight male SD rats were randomly divided into four groups: normal group, ALI group, low tidal volume (V(T)) group (LV group) and low V(T)+SI group (SI group). After 4 hours of mechanical ventilation, lung injury was evaluated by Smith lung injury score. Extravascular lung water (EVLW) was measured by gravimetric method. Alveolar epithelium apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). mRNA expression of surfactant protein (SP)-C was assessed by reverse transcription polymerase chain reaction (RT-PCR). Interleukin (IL-6) and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Injury degree of lung tissues in SI group was lighter than those of ALI and LV groups under microscope. A few of apoptotic epithelial cells were observed in SI group (all P<0.05). Compared with LV group, apoptotic epithelial cells were decreased in number in SI group. Smith lung injury score and EVLW in ALI, LV and SI group were higher than those in the control group. Smith lung injury score in ALI group was significantly higher than the score in SI and LV group (both P<0.05). Smith lung injury score and EVLW of SI group were significantly lower than those of LV group (both P<0.05). There was no significant difference in EVLW between SI and ALI group. The SP-C mRNA expression was significantly lowered in ALI, LV and SI groups compared with that in control group (all P<0.05). The SP-C mRNA expression in SI group was stronger than LV group significantly (P<0.05), but not significant when compared with that of ALI group. The concentrations of IL-6 and IL-10 in BALF of ALI, LV and SI groups were significantly higher than those of control group (all P<0.05). In SI group, the concentration of IL-6 in BALF was lower than LV group (P<0.05). There was no difference in the permeability of alveolar epithelium among ALI, LV and SI groups. CONCLUSION: RM can alleviate lung tissue injury, up-regulate SP-C mRNA expression in alveolar epithelium, protect alveolar epithelium barrier and down-regulate pulmonary inflammatory mediator expression in ALI.

[Value of preoperative pulmonary artery diastolic pressure on predicting primary graft dysfunction after bilateral lung transplantation for patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF). METHODS: A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation. RESULTS: Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGD group, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non-PGD group [PADP ahead of operation (mmHg, 1 mmHg = 0.133 kPa): 33.7±10.5 vs. 25.3±10.1, mPAP ahead of operation (mmHg): 40.4±14.1 vs. 32.8±11.1, the dosage of red cells suspension after the operation (mL): 700 (300, 1 500) vs. 300 (300, 500), the total amount of blood transfusion during and after the operation (mL): 2 250 (1 850, 4 275) vs. 1 800 (1 550, 2 800)], with statistically significant differences (all P < 0.05). There were no significant differences in age, gender, BMI, underlying disease, NT-proBNP before operation, PASP before and after operation, PADP and mPAP after operation, duration of operation, amount of plasma and red cells suspension as well as total amount of blood transfusion during operation, plasma amount and total amount of blood transfusion after operation, amount of plasma and red cells suspension during and after operation, use of ECMO during operation, blood purification treatment after operation, and shock after operation between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that the preoperative PADP was the independent risk factor of grade 3 PGD after lung transplantation [odds ratio (OR) = 1.084, 95% confidence interval (95%CI) = 1.016-1.156, P = 0.015]. It was shown by ROC curve that the area under the ROC curve (AUC) of the PADP before operation for predicting the grade 3 PGD after lung transplantation was 0.728. When the cut-off value was 36 mmHg, the sensitivity was 47.1%, and the specificity was 91.4%. CONCLUSIONS: Compared with the non-PGD group, the patients with higher preoperative PADP were more common in the PGD group, and the patients in the PGD group were more likely to be characterized by grade 3 PGD after lung transplantation. The preoperative PADP was an effective predictor of grade 3 PGD after lung transplantation.

Experimental study of airway pressure release ventilation in the treatment of acute respiratory distress syndrome.

Airway pressure release ventilation (APRV) is a ventilator mode which has demonstrated potential benefits in acute respiratory distress syndrome (ARDS) patients. We therefore sought to compare relevant pulmonary data and safety outcomes of this mode to the conventional ventilation and sustained inflation. Canines admitted after intravenous injection of oleic acid requiring mechanical ventilation were randomly divided into 3 groups (n=6), namely conventional ventilation group, low tidal volume ventilation with recruitment group (LTV+SI) and APRV group. The changes of oxygenation, ventilation, airway pressure, inflammatory reaction and hemodynamics at the basic state were observed at 0, 1, 2 and 4 h during the experiment. The levels of PaO2/FiO2 in APRV group were higher than LTV+SI group at 2 and 4 h (P<0.05). In APRV group, the PCO2 levels at 1, 2 and 4 h is much lower than LTV+SI group (P<0.05). Outcome variables showed no differences between APRV, LVT+SI and conventional mechanical ventilation for plateau airway pressure (24±1 vs. 29±3 vs. 25±4), mean arterial pressure (92.9±16.5 vs. 85.8±21.4 vs. 88.7±24.4), cardiac index (4.3±1.7 vs. 3.5±1.9 vs. 3.4±2.1), ERO2 (13.4±10.3 vs. 16.1±6.8 vs. 17.6±9.1), lac (2.5±1.7 vs. 3.1±1.6 vs. 3.9±1.9), tumor necrosis factor (TNF)-α (132±11 vs. 140±6 vs. 195±13) and matrix metalloproteinase (MMP)-9. For canines sustaining acute respiratory distress syndrome requiring mechanical ventilation, APRV can significantly improve oxygenation and keep hemodynamic stability compared with LTV+SI. The results of TNF-α and MMP-9 suggest that APRV could be as protective for ARDS as LTV with recruitment group.

[Relationship of stress index with lung recruitment and gas exchange in dogs with acute respiratory distress syndrome].

OBJECTIVE: To determine the relationship of stress index with lung recruitment and gas exchange in dogs with acute respiratory distress syndrome (ARDS). METHODS: The ARDS model was induced by infusion of oleic acid intravenously in anesthetized dogs. During volume control ventilation with constant inspiratory flow, the pressure-time (P-t) curve was fitted to a power equation: P = a.time(b)+c, where coefficient b (stress index) describes the shape of the curve: b = 1, straight curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in slope. Tidal volume (V(T)) was 6 ml/kg, and positive end-expiratory pressure (PEEP) was set to obtain a b value between 0.9 and 1.1 before (b = 1) and after (b = 1 after recruiting maneuver) application of a recruiting maneuver (RM). PEEP was changed to obtain 0.6 < b < 0.8 and 1.1 < b < 1.3. Experimental condition sequence was random. Recruited volume (RV) was measured by static pressure-volume curve method. Hemodynamics, pulmonary mechanics and gas exchange were observed at the same time. RESULTS: At b = 1 without RM, the PEEP was (5.0 +/- 3.0) cm H2O, the RV was (27 +/- 15) ml, and the RV increased to (166 +/- 84) ml significantly at b = 1 after RM [PEEP (10.8 +/- 2.3) cm H2O (1 cm H2O = 0.098 kPa), q = 3.18, P < 0.01]. At 1.1 < b < 1.3 after RM, the PEEP was (16.8 +/- 1.1) cm H2O and the RV was (262 +/- 57) ml, which was higher than that at b = 1 after RM (q = 2.54, P = 0.023). At 0.6 < b < 0.8 after RM, the PEEP was (5.6 +/- 2.2) cm H2O and the RV was lower than that at b = 1 after RM (q = 2.85, P = 0.013). The partial pressure of oxygen in arterial blood (PaO2) in b = 1, 0.6 < b < 0.8 and 1.1 < b < 1.3 after RM were (319 +/- 49) mm Hg (1 mm Hg = 0.133 kPa), (246 +/- 57) mm Hg and (314 +/- 27) mm Hg respectively, which was higher than the PaO2 at b = 1 without RM [(153 +/- 64) mm Hg, all q = 2.81, all P < 0.05]. The PaO2 at 0.6 < b < 0.8 was lower than that at b = 1 after RM (q = 2.81, P = 0.005), while there was no significant difference between the PaO2 at 1.1 < b < 1.3 and that at b = 1 after RM. The peak airway pressure and plateau pressure at 1.1 < b < 1.3 were higher than those at b = 1 after RM (q = 6.02, 5.72, all P < 0.05). CONCLUSION: In the b = 1 after RM, there were better PaO2 and lower airway pressure, suggesting that b = 1 after RM may be a good indicator for PEEP titration.

[Assessment of stroke volume variation and intrathoracic blood volume index on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock].

OBJECTIVE: To assess the significance of stroke volume variation (SVV) and intrathoracic blood volume index (ITBI) on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock. METHODS: Hemorrhagic shock canine model was established with the modified Wiggers' method. The heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), intrathoracic blood volume index (ITBI) and stroke volume variation (SVV) were investigated by Swan-Ganz catheter or PiCCO monitor. Graded volume loading (VL) was performed. Successive responsive VLs were performed (increase in SV > 5% after VL) until continuous change in SV < 5% (unresponsive) was reached. RESULTS: Fourteen canines were studied and a total of 134 VLs were performed. In 94 VLs, an increase in SV of more than 5% was reached. In the other 40 VLs, increase in SV was less than 5%. The change of HR, MAP, ITBI, SVV in responsive were more than those of unresponsive after VL. The change of CVP, PAWP in responsive were less than those of unresponsive. Significant correlation was found between DeltaSV after VL and the baseline values of ITBI, SVV. No correlation was found between DeltaSV and HR, MAP, CVP, PAWP. Significant correlations were also found between DeltaSV and DeltaCVP, DeltaPAWP, DeltaITBI, DeltaSVV after fluid loading. No correlation was found between DeltaSV and DeltaHR, DeltaMAP. By using receiver operating characteristic analysis, the area under the curve were 0.872 for SVV and 0.689 for ITBI, more than those of HR, MAP, CVP, PAWP statistically. As SVV value of 9.5% or more will predict an increase in the SV of at least 5% in response to a VL with a sensitivity of 92.6% and a specificity of 82.5%. CONCLUSIONS: SVV and ITBI were more useful indicators than CVP and PAWP on the assessment of responsiveness to volume loading. SVV as a functional preload parameter and for on-line monitoring may help to improve the hemodynamic management.

[Effect of lung stress index on titration of positive end-expiratory pressure at post-recruitment in three canine acute respiratory distress syndrome models].

OBJECTIVE: To investigate the relationship of lung stress index and positive end-expiratory pressure (PEEP) at post-recruitment in different canine acute respiratory distress syndrome (ARDS) models. METHODS: The ARDS models were induced by intravenous oleic acid, saline lavage and hydrochloric acid aspiration in anesthetized dogs. During volume control ventilation with constant inspiratory flow, PEEP was set to obtain a b (stress index) value between 0.9 and 1.1 (b = 1) before and post recruitment maneuver (RM). PEEP was changed to obtain b < 1 (0.6 < b < 0.8) and b > 1 (1.1 < b < 1.3). Meanwhile, the recruited volume (RV) was measured and pulmonary mechanics and gas exchange were observed. RESULTS: At b = 1 after RM, PEEP were (10.8 +/- 2.3), (12.8 +/- 1.8) and (9.2 +/- 1.8) cm H2O in the oleic acid, saline-lavaged and hydrochloric acid aspiration groups, respectively. PEEP in saline-lavaged group was higher than that in hydrochloric acid aspiration group (P < 0.05). The ratio of partial arterial oxygen tension and fraction of inspiratory oxygen (PaO(2)/FiO(2)) at b = 1 without RM was lower than those post-RM in all three groups (P < 0.05). In oleic acid group, PaO(2)/FiO(2) at b = 1 post-RM was (399 +/- 61) mm Hg, which was higher than that at b < 1 [(307 +/- 71) mm Hg], but there was no difference between those at b = 1 and b > 1. At b = 1 after RM, PaO(2)/FiO(2) in the saline-lavaged group was higher than that in acid aspiration group, but no difference between saline-lavaged group and oleic acid group was found. At b = 1 post-RM, RV were higher than that at b = 1 before RM in all three groups (P < 0.01), but there was no significant difference among three groups. At b = 1 post-RM in three groups, pulmonary compliance were higher than those at b > 1, but airway plateau pressure were lower than those at b > 1. CONCLUSIONS: Lung stress index could be a good indicator for PEEP titration at post-RM.

[Comparison of single-indicator thermodilution versus gravimetric measurement in determination of extra-vascular lung water in dogs with acute respiratory distress syndrome].

OBJECTIVE: To compare the measurement of extra-vascular lung water (EVLW) by a single-indicator dilution technique and measurement obtained by gravimetry in different types of acute respiratory distress syndrome (ARDS). METHODS: Thirty-three dogs were randomly assigned to three groups: control group, oleic acid group and hydrochloric acid group. ARDS was reproduced by either intravenous injection of oleic acid or intratracheal instillation of hydrochloric acid. EVLW was measured before ARDS, at the onset of ARDS and 10 hours after ARDS by a single indicator dilution technique. Ten hours after ARDS, dogs were sacrificed and then EVLW was quantitated by a gravimetric measurement (golden standard). Hemodynamics and pulmonary gas exchange were determined. RESULTS: There was a close positive correlation (r=0.8820, P<0.05) between single indicator dilution and gravimetric measurements. However, the measurement with the single indicator dilution was consistently higher than the gravimetric measurement. In the control group, there was a positive correlation (r=0.9870, P<0.05) between the values of EVLW as measured by single indicator dilution and by gravimetric measurements. In the oleic acid group, there was also a significant correlation (r=0.9360, P<0.05) between the values of EVLW as measured by single indicator dilution and by gravimetric measurements. In the hydrochloric acid group, correlation (r=0.7950, P<0.05) was also found between EVLW as measured by the two methods. However, the correlation found was lower in the hydrochloric acid group than those in other two groups. Hydrochloric acid instillation resulted in a significant increase in shunting and the partial pressure of carbon dioxide in artery (PaCO(2)) compared with oleic acid group at 10 hours after ARDS. CONCLUSION: The results of measuring EVLW using single indicator dilution measurement are closely related with those of gravimetric measurement in ARDS, however, the correlations varies with the methods of reproduction of ARDS.

Effect of setting high APRV guided by expiratory inflection point of pressure-volume curve on oxygen delivery in canine models of severe acute respiratory distress syndrome.

In the present study, the effect of setting high airway pressure release ventilation (APRV) pressure guided by an expiratory inflection point of pressure-volume (PV) curve following lung recruitment maneuver (RM) on oxygen delivery (DO2) in canine models of severe acute respiratory distress syndrome (ARDS) was examined. Canine models of severe ARDS were established by intravenous injection of oleic acid. After injection of sedative muscle relaxants, a PV curve plotted using the super-syringe technique, and the pressure at lower inflection point (LIP) at the inhale branch and the pressure at the point of maximum curvature (PMC) at the exhale branch were measured. The ventilation mode was biphasic positive airway pressure (BiPAP), an inspiration to expiration ratio of 1:2, and Phigh 40 cm H2O, Plow 25 cm H2O. Phigh was decreased to 30 cm H2O after 90 sec. The dogs were randomized into 3 groups after RM, i.e., Blip group, BiPAP Plow = LIP+2 cm H2O; Bpmc group, BiPAP Plow = PMC; and Apmc group. In the APRV group, Phigh was set as PMC, with an inspiratory duration of 4 sec and expiratory duration of 0.4 sec. PMC was 18±1.4 cm H2O, and LIP was 11±1.3 cm H2O. Thirty seconds after RM was stabilized, it was set as 0 h. Hemodynamics, oxygenation and DO2 were measured at 0, 1, 2 and 4 h after RM in ARDS dogs. The results demonstrated: i) cardiac index (CI) in the 3 groups, where CI was significantly decreased in the Bpmc group at 0, 1, 2 and 4 h after RM compared to prior to RM (P<0.05) as well as in the Blip and Apmc groups (P<0.05). CI in the Blip and Apmc groups was not significantly altered prior to and after RM. ii) Oxygenation at 0, 1, 2 and 4 h in the 3 groups was improved after RM and the oxygenation indices for the 3 groups at 1 and 2 h were not significantly different (P>0.05). However, the oxygenation index in the Blip group at 4 h was significantly lower than those at 0 h for the Apmc and Bpmc groups (P<0.05). Oxygenation for the Apmc group at 4 h was higher than that for the Blip and Bpmc groups (P<0.05). Oxygenation for the Bpmc group was lower than that at 0 h, although the difference was not significant (P>0.05). iii) DO2 in at 0, 1, 2 and 4 h in the Bpmc group was significantly lower than that in the Blip and Apmc groups, and not significantly improved after RM. DO2 in the Blip and Apmc groups after RM was improved as compard to that before RM and that in the Bpmc group. However, DO2 at 4 h in the Blip group was significantly lower than that at 0 h and in the Apmc group (P<0.05). DO2 at 4 h in the Apmc group was higher than that at 0 h and that in the remaining 2 groups (P<0.05). In conclusion, high APRV pressure guided at PMC of PV curve after RM significantly improved DO2 in ARDS dogs.