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Objective To evaluate the role of calcineurin ( CaN)/nuclear factor of activated T cell cytoplasmic 4 protein ( NFATc4) signaling pathway in inflammatory responses in lung tissues of rats with ventilator-induced lung injury ( VILI) . Methods Twenty-four clean-grade healthy male Wistar rats, aged 5-8 weeks, weighing 220-250 g, were divided into 3 groups ( n=8 each) using a random number table method: control C (group C), VILI group and cyclosporine A plus VILI group (group CsA+VILI). The animals were anesthetized with pentobarbital and tracheostomized. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml/kg and respiratory rate at 40 breaths/min to establish the model of VI-LI. The rats kept spontaneous breathing in group C. CaN specific inhibitor cyclosporine A 10 mg/kg was in-traperitoneally injected at 1 h before ventilation in group CsA+VILI. Rats were sacrificed immediately after ventilation, lung tissues were obtained and stained with hematoxylin and eosin to evaluate lung injury, broncho-alveolar lavage fluid was collected for determination of tumor necrosis factor-alpha ( TNF-α) , inter-leukin-1beta ( IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay, and the lungs were removed for determination of the wet to dry weight ratio ( W/D ratio) , expression of intercellular adhesion molecule-1 ( ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) ( by real-time polymerase chain reaction) , and expression of calcineurin and NFATc4 in lung tissues ( using Western blot ) . Results Compared with group C, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly increased, and the expression of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was up-regulated in group VILI ( P＜0. 05) . Compared with group VILI, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly decreased, and the expres-sion of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was down-regulated in group CsA+VILI ( P＜0. 05) . Conclusion CaN/NFATc4 signaling pathway mediates inflammatory responses in lung tissues of rats with VILI.
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Objective To evaluate the effect of γ-aminobutyric acid (GABA) preconditioning on pathological stretch-induced damage to type Ⅱ alveolar epithelial cells by mechanical ventilation.Methods A549 cells cultured in vitro (0.2× 106/ml,2.5 ml/well) were randomly divided into 3 groups using a random number table:control group (group C),pathological stretch group (group P) and GABA preconditioning+pathological stretch group (group G).A549 cells were exposed to 20％ cyclic stretch at 0.3 Hz for 6 h in groups P and G;GABA 50 μmol/L was given 30 min before cyclic stretch in group G.After the end of pathological stretch,the cells were collected for determination of the cell viability by methyl thiazolyl tetrazolium assay and lactate dehydrogenase (LDH) release by colorimetricmethod;the expression of F-actin was observed with indirect immunofluorescence;the expression of Rho-associated kinase 1 (ROCK1) and GABAAR were determined by western blot.Results Compared with group C,the cell viability was significantly decreased,the amount of LDH released was increased,the expression of ROCK1 was significantly increased and the expression of GABAAR was significantly decreased in groups P and G (P＜0.05);Compared with group P,the cell viability was significantly increased,the amount of LDH released was decreased,F-actin was re constructed,the expression of ROCK1 was significantly decreased and the expression of GABAAR was significantly increased (P＜0.05) in group G.The reconstruction of F-actin in group P was better than that in group G and worse than that in group C.Conclusion GABA preconditioning can attenuate pathological stretch-induced damage to type Ⅱ alveolar epithelial cells probably through up regulating the expression of GABAA receptor.
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Objective To evaluate the accuracy of respiratory variations of internal jugular vein (IJV) in monitoring fluid responsiveness in patients undergoing radical gastrectomy for gastric cancer.Methods Fifty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 40-64 yr,scheduled for elective radical gastrectomy for gastric cancer,were enrolled in this study.Before induction of anesthesia,the hemodynamic parameters such as heart rate,central venous pressure,cardiac index,stroke volume index (SVI),stroke volume variation and respiratory variation of IJV were recorded after haemodynamics was stable and were recorded again at 10 min after endotracheal intubation,and a loading dose of 6％ 130/0.4 hydroxyethyl starch 7 ml/kg was infused over 15 min.The parameters mentioned above were recorded within 5 min after loading dose.Patients were divided into 2 groups according to the percentage of increase in SVI (△SVI) after volume expansion:△SVI≥ 15％ was considered to be a positive response (responder group) and △SVI＜15％ was considered to be a negative response after volume expansion (non-responder group).Results The area under the receiver operating characteristic curve of respiratory variations of IJV in monitoring fluid responsiveness and 95％ confidence interval were 0.852 (0.744-0.961).Respiratory variation of IJV 24.6％ was considered as the cut-off value and used to monitor fluid responsiveness,and the sensitivity and specificity were 67.6％ and 92.3％,respectively.Conclusion Respiratory variation of IJV can be considered as an effective index in monitoring fluid responsiveness in the patients undergoing radical gastrectomy for gastric cancer.
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Objective To evaluate the effect of dexmedetomidine on the expression of gamma-aminobutyric acid(GABAA)receptors during ventilator-induced lung injury(VILI)in rats. Methods Thirty pathogen-free adult male Sprague-Dawley rats,weighing 280-320 g,were divided into 3 groups(n=10 each)using a random number table:control group(group C),group VILI and dexmedetomidine group(group Dex).The rats were mechanically ventilated for 4 h with the tidal volume of 40 ml/kg to establish VILI model. Dexmedetomidine 50 μg/kg was injected intraperitoneally after the rats were anesthetized in group Dex,while the equal volume of normal saline was given instead in C and VILI groups. The animals were sacrificed at 4 h of mechanical ventilation,the lungs were removed for examination of pathological changes which were scored,bronchoalveolar lavage fluid(BALF)was collected for determination of concentrations of total protein,interleukin-1 beta(IL-1β),IL-6 and tumor necrosis factor-alpha(TNF-α),and the lung specimens were obtained for determination of the wet/dry weight ratio(W/D ratio),alveolar fluid clearance(AFC)and expression of GABAA receptors,IL-1β,IL-6 and TNF-α mRNA in lung tissues. Results Compared with group C,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly increased,and the GABAA receptor expression and AFC were decreased in VILI and Dex groups(P<0.05).Compared with group VILI,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly decreased,and the GABAA receptor expression and AFC were increased in group Dex(P<0.05).Conclusion The mechanism by which dexmedetomidine reduces VILI is related to up-regulation of GABAA receptor expression in rats.
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Objective To evaluate the effect of ulinastatin on γ-aminobutyric acid (GABA) signal pathway in mice with ventilator-induced lung injury (VILI).Methods Thirty-six male Wister mice were randomly divided into 3 groups using a random number table:control group (group C), ventilator-induced lung injury group (group VILI),and ventilator-induced lung injury+ ulinastatin group (group UTI),n =12 in each group.VILI was induced by 4 h mechanical ventilation with tidal volume 40 ml/kg in groups VILI and UTI.Ulinastatin 1×10 5 U/kg was injected intraperitoneally 1 h before ventilation in group UTI,while the equal volume of normal saline was given in groups C and VILI.The mice were then sacrificed,the left lung was lavaged,and broncho-alveolar lavage fluid (BALF)was collected for determination of concentrations of protein,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and intercellular adhesion molecule-1 (ICAM-1).The lung tissues were re-moved for determination of the wet to dry lung weight (W/D)ratio,the mRNA expression level of IL-1β,TNF-αand ICAM-1.The pathological changes of the lungs were determined under light micro-scope and the lung injury scores were also determined.Immunohistochemistry and Western blot were used to detected the protein expression level of GAD and GABAA R.Results The W/D ratio (6.7 ± 2.4 vs.8.5±2.3)and lung scores [(6.9±2.3)scores vs.(1 1.8±2.7)scores]were significantly de-creased in group UTI than those in group VILI.The concentrations of IL-1β[(56±1 1)ng/L vs.(77 ±1 5)ng/L],TNF-α[(105±29)ng/L vs.(1 58±37)ng/L]and ICAM-1 [(205±46)ng/L vs.(293 ±61)ng/L]in BALF in group UTI were significantly decreased than those in group VILI.The mRNA ex-pression levels of IL-1β(1.81±0.26 vs.2.58±0.34),TNF-α(1.61±0.15 vs.2.94±0.27)and ICAM-1 (1.74±0.27 vs.2.79±0.31)were significantly decreased in group UTI than those in group VILI.The protein expression levels of GAD (0.44±0.08 vs.0.18 ±0.04)and GABAA R (0.30 ±0.09 vs.0.15 ± 0.04)were significantly increased in group UTI than those in group VILI.Conclusion Ulinastatin can at-tenuate VILI probably through activating GABA signaling pathway.
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Objective To evaluate the accuracy of respirophasic variation in carotid artery blood flow peak velocity(ΔVpeak-CA)in predicting fluid responsiveness in the patients undergoing surgery in the prone position. Methods Forty-three American Society of Anesthesiologists physical status Ⅰ-Ⅲ pa-tients of both sexes, aged 45-75 yr, with body mass index of 20-25 kg∕m2, scheduled for elective posteri-or approach lumbar surgery, were enrolled in the study.After induction of anesthesia, hydroxyethyl starch 130∕0.4 sodium chloride injection 7 ml∕kg was intravenously infused over 20 min when the patients were in the prone position.Subjects were classified as responders if stroke volume index increased≥15% after vol-ume expansion.The receiver operating characteristic curve for ΔVpeak-CA in determining positive fluid re-sponsiveness was drawn. Results The results of receiver operating characteristic curve analysis showed that: the cut-off value of ΔVpeak-CA in predicting positive fluid responsiveness was 7.94%, sensitivity 81.8%, specificity 70.0%, and the area under the curve(95% confidence interval)was 0.818 (0.378-0.757). Conclusion Respirophasic ΔVpeak-CA can accurately predict fluid responsiveness in the patients undergoing surgery in the prone position.
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Objective To evaluate the relationship between the shedding of syndecan-4(SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups(n=10 each)using a random number table:control group(group C), mechanical ventilation with traditional tidal volume(VT)group(group T-VT) and mechanical ventilation with high VTgroup(group H-VT). The animals were anesthetized with pento-barbital sodium and tracheostomized. The rats kept spontaneous breathing in group C. The rats were me-chanically ventilated for 4 h with the VTset at 6 ml∕kg in group T-VT and with the VTset at 40 ml∕kg in group H-VT. Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta(IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay. The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues(by Western blot and real-time polymerase chain reaction, respectively)and for examination of the pathological changes. The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in bron-cho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT(P<005), and no significant change was found in the parameters mentioned above in group T-VT(P>005).Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats.
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Objective To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative cognitive function in the patients undergoing intracranial tumor resection.Methods One hundred patients of both sexes,aged 45-64 yr,weighing 50-70 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective cerebral glioma or meningioma resection,were randomly divided into 2 groups (n=50 each) using a random number table:GDFT group (group G) and conventional fluid therapy group (group C).The mean arterial pressure was maintained at 65-110 mmHg,urine volume ＞0.5 ml · kg-1 · h-1,and central venous pressure at 8-12 cmH2O in group C.In group G,GDFT was performed using FloTrac/Vigileo system,and the cardiac index was maintained at 2.5-4.0 L · min-1 · n 2,stroke volume variation≤ 13％,mean arterial pressure at 65-110 mmHg,and stroke volume index at 35-47 ml/m2.The requirement for crystalloid and colloid,urine volume,blood loss,and requirement for vasoactive agents were recorded during operation.Before induction of anesthesia (baseline),when the dura of brain was opened,at the end of tumor removal,at the end of operation,and at 24 h after operation (T0-4),venous blood samples were taken to determine the concentrations of serum neuron-specific enolase (NSE) and S100β protein by enzyme-linked immunosorbent assay.The patient's cognitive function was assessed using Mini-Mental State Examination at T0 and 7 days after operation (T5).Results Compared with the baseline value at T0,the serum NSE and S100β protein concentrations were significantly increased at T24 in the two groups (P＜0.05).Compared with group C,the requirement for colloid,total volume of fluid infused and urine volume during operation were significantly increased,the serum NSE and S100β protein concentrations were significantly decreased at T3,4 (P＜0.05),and no significant change was found in Mini-Mental State Examination score at T0 and T5 in group G (P＞0.05).Conclusion GDFT based on FloTrac/Vililgeo system can reduce the damage to brains after operation,but it has no significant effect on postoperative cognitive function in the patients undergoing intracranial tumor resection.
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Objective To evaluate the effect of dexmedetomidine on janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in mice with endotoxin-induced acute lung injury (ALI).Methods Twenty-four male C57BL/6 mice,weighing 20-25 g,were randomly divided into 3 groups (n=8 each) using a random number table:control group (group C),endotoxin-induced ALI group (group ALI),and dexmedetomidine group (group Dex).ALI was induced with lipopolysaccharide (LPS) 5 mg/kg injected intraperitoneally.Dexmedetomidine 40 μg/kg was injected intraperitoneally at 1 h after LPS injection in group Dex,while the equal volume of normal saline was given in C and ALI groups.At 6 h after LPS injection,blood samples were collected from the carotid artery to detect arterial oxygen partial pressure (PaO2).The mice were then sacrificed,and broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of total protein,interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-or (TNF-α).The lung tissues were removed for determination of wet to dry lung weight ratio (W/D ratio),and expression of phosphorylated JAK2 (p-JAK2),phosphorylated STAT3 (p-STAT3),IL-1β mRNA,IL-6 mRNA and TNF-α mRNA,and for examination of the pathological changes which were scored.Results Compared with group C,the PaO2 was significantly decreased,and W/D ratio,lung injury score,concentrations of total protein,IL-1β,IL-6 and TNF-α in BALF,and expression of IL-1β,IL-6 and TNF-α mRNA,p-JAK2 and p-STAT3 were increased in ALI and Dex groups (P＜0.05).Compared with group ALI,the PaO2 was significantly increased,and W/D ratio,lung injury score,concentrations of total protein,IL-1β,IL-6 and TNF-α in BALF,and expression of IL-1β,IL-6 and TNF-α mRNA,p-JAK2 and p-STAT3 were decreased in group Dex (P＜0.05).Conclusion The mechanism by which dexmedetomidine attenuates LPS-induced ALI is probably related to inhibition of activation of JAK2/STAT3 signaling pathway in mice.
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Objective To evaluate the effect of dexmedetomidine on microRNA (miRNA)-155-hypoxia-inducible factor-1α (HIF-1α)-heme oxygenase-1 (HO-1) signaling pathway in a rat model of endotoxin-induced acute lung injury.Methods Forty adult male Wistar rats,weighing 220-250 g,were equally and randomly divided into 4 groups using a random number table:control group (group C),dexmedetomidine group (group D),endotoxin-induced acute lung injury group (group L),and endotoxin-induced acute lung injury+dexmedetomidine group (group LD).Acute lung injury was induced by intraperitoneal lipopolysaccharide (LPS) 5 mg/kg in L and LD groups.In D and LD groups,dexmedetomidine was infused in a loading dose of 1 μg · kg-1 · h-1 for 10 min starting before intraperitoneal injection of normal saline or LPS followed by an infusion of 5 μg · kg-1 · h-1 throughout the operation.At 6 h after normal saline or LPS injection,blood samples were taken from the carotid artery for detection of arterial oxygen partial pressure (PaO2).The left lung was lavaged,and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of total protein,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α),and intercellular adhesion molecule-1 (ICAM-1).The rats were then sacrificed,and lungs were removed for determination of the wet to dry lung weight ratio (W/D ratio),mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1,and for examination of the pathological changes which were scored.Results Compared with group C,the PaO2 was significantly decreased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1 were significantly increased in L and LD groups (P ＜ 0.05).Compared with group L,the PaO2 and protein expression of HIF-1α and HO-1 were significantly increased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,and mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1 were significantly decreased in group LD (P＜0.05).Conclusion Dexmedetomidine reduces endotoxin-induced acute lung injury through activating miR-155-HIF-1α-HO-1 signaling pathway in rats.
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Objective To evaluate the role of spinal RhoA/ROCK signaling pathway in the development of lipopolysaccharide (IP)-induced inflammatory pain(IP) in rats.Methods Fifty-two male Sprague-Dawley rats, weighing 180-220 g, were equally randomized into 4 groups using a random number table: normal saline group (group NS) , LPS group, RhoA inhibitor C3 exoenzyme group (group LC) , and ROCK inhibitor Y27632 group (group LY).Inflammatory pain was induced by injecting LPS 25 μl (300 ng) into the plantar surface of hindpaws in IP, LC and LY groups, while the equal volume of normal saline was injected instead in NS group.C3 exoenzyme 10 pg and Y27632 10 nmol were injected intrathecally at 30 min prior to LPS administration in LC and LY groups, respectively.Before LPS injection (T0) , and at 1, 3, 5, 12 and 24 h after LPS injection (T1-5) , the mechanical and thermal pain thresholds were measured.Five rats in each group were sacrificed after pain thresholds were measured at T3, and L4.5 segments of the spinal cord were removed for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression in spinal dorsal horns by real-time reverse transcriptase-polymerase chain reaction.Results Compared with group NS, the mechanical and thermal pain thresholds were significantly decreased at T2-5in IP, LC and LY groups, and TNF-α and IL-1β mRNA expression was up-regulated at T3 in IP group.Compared with group IP, the mechanical and thermal pain thresholds were significantly increased at T2-5, and TNF-α and IL-1β mRNA expression was down-regulated at T3 in LC and LY groups.Conclusion Spinal RhoA/ROCK signaling pathway is involved in the development of LPS-induced IP in rats.
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Objective To evaluate the effects of mechanical stretch preconditioning on pathological stretch-induced activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways in human type Ⅱ alveolar epithelial cells.Methods Human type Ⅱ alveolar epithelial cell line A549 cells cultured in vitro were randomly divided into 3 groups (n =24 each) using a random number table: control group (group Ⅰ), pathological stretch group (group Ⅱ), and mechanical stretch preconditioning group (group Ⅲ).In group Ⅰ , A549 cells were cultured routinely without receiving pathological stretch.In group Ⅱ , A549 cells were exposed to 20％ cyclic stretch at 0.3 Hz for 6 h.In group Ⅲ , A549 cells were exposed to 5％ cyclic stretch at 0.3 Hz for 60 min, and then exposed to 20％ cyclic stretch at 0.3 Hz for 6 h.After the end of the treatment, the cells were collected for determination of the cell viability (by methyl thiazolyl tetrazolium assay) and lactate dehydrogeuase (LDH)release (by colorimetric method).The concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-8 (IL-8) and high mobility group box 1 (HMGB1) in the culture medium were detected using enzyme linked immunosorbent assay.The expression of total NF-κB, phosphorylated NF-κB, total STAT3 and phosphorylated STAT3 was detected using Western blot.The ratios of phosphorylated NF-κB to total NF-κB and phosphorylated STAT3 to total STAT3 were calculated to reflect the activation.Results Compared with group Ⅰ , the cell viability was significantly decreased, the amount of LDH released was increased, and the concentrations of TNF-α, IL-8 and HMGB1, and activation of NF-κB and STAT3 were increased in Ⅱ and Ⅲ groups.Compared with group Ⅱ , the cell viability was significantly increased, the amount of LDH released was decreased, and the concentrations of TNF-α, IL-8 and HMGB1, and activation of NF-κB and STAT3 were decreased in group Ⅲ.Conclusion The mechanism by which mechanical stretch preconditioning attenuates pathological stretch-induced damage to human type Ⅱ alveolar epithelial cells is related to inhibited activation of NF-κB and STAT3 signaling pathways.
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Objective To evaluate the protective effects of lung protective ventilation on the lungs in patients undergoing radical resection for esophageal cancer.Methods Sixty-eight patients of both sexes,aged 40-64 yr,of ASA physical status Ⅰ or Ⅱ,with body mass index 17-40 kg/m2,scheduled for elective radical resection for esophageal cancer,were randomly divided into conventional ventilation group (CV group,n =34) and protective ventilation group (PV group,n =34) using a random number table.Double lumen tube was inserted after induction of anesthesia,an anesthesia machine was connected,and the patients were mechanically ventilated.In group CV,VT was set at 10 ml/kg during two-lung ventilation,and VT was set at 7 ml/kg,and I ∶ E was set at 1 ∶ 2 during one-lung ventilation.In group PV,VT was set at 7 ml/kg during two-lung ventilation,VT was set at 5 ml/kg,I ∶ E was set at 1 ∶ 2,and PEEP was set at 10 cmH2O during one-lung ventilation,and bilateral lung recruitment maneuver was performed every 45 min.Before induction of anesthesia,and at days 1,3,and 5 after surgery,blood gas analysis was performed,and Clinical Pulmonary Infection Score was recorded.Before induction of anesthesia,and at 5 days after surgery,point-of-care testing for pulmonary function was performed,and percentages of maximum ventilatory volume (MVV％),forced vital capacity (FVC％),and forced expiratory volume in 1 second (FEV1％) were recorded,and FEV1/FVC was calculated.The development of respiratory failure,pulmonary atelectasis and incision infection was recorded within 5 min after surgery.Results Compared with group CV,MVV％,FVC％,FEV1％ and FEV1/FVC were significantly increased,Clinical Pulmonary Infection Score was decreased at each time point after surgery,SaO2 and PaO2 were increased,and no significant changes were found in pulmonary atelectasis and incision infection in group PV.Conclusion Lung protective ventilation can effectively protect the lungs in the patients undergoing radical resection for esophageal cancer.
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Objective To evaluate the effects of mechanical ventilation preconditioning on the expression of Rho-associated kinase 1 (ROCK1) in the lung tissue in a rat model of ventilator-induced lung injury.Methods Forty-eight male Sprague-Dawley, aged 8-12 weeks, weighing 250-300 g, were randomly assigned into 6 groups (n =8 each) using a random number table: control group (group C);normal mechanical ventilation group (group N);mechanical ventilation with large tidal volume (VT) group (group L);preconditioning with mechanical ventilation with different VT groups (P1, P2 and P3 groups).The animals were anesthetized with intraperitoneal pentobarbital sodium, and tracheostomized.In group C, the animals kept spontaneous breathing after intubation.In group N, the animals were mechanically ventilated for 3 h with the VT of 8-10 ml/kg.In group L, the animals were mechanically ventilated for 3 h with the VT of 40 ml/kg.In P1, P2 and P3 groups, the animals were mechanically ventilated for 30 min with the VT of 6-7, 20 and 30 ml/kg, respectively, and then were mechanically ventilated for 3 h with the VT of 40 ml/kg.The respiratory rate was 40 breaths/min, and inspiratory/expiratory ratio was 1 : 1.The animals were sacrificed at the end of ventilation.Broncho-alveolar lavage fluid was collected, and pulmonary permeability index (PPI) was calculated.Lungs were removed for examination of pathological changes which were scored,and for detection of the wet to dry lung weight ratio (W/D ratio), apoptosis in alveolar epithelial cells, and expression of ROCK1 (by immunohistochemistry and Western blot).Apoptosis index (AI) was calculated.Results Compared with group C, the pathological scores, W/D ratio, PPI and AI were significantly increased, and the expression of ROCK1 was up-regulated in L, P1, P2 and P3 groups (P＜0.05) , and no significant change was found in the parameters mentioned above in group N (P＞0.05).Compared with group L, the pathological scores, W/D ratio, PPI and AI were significantly decreased, and the expression of ROCK1 was down-regulated in group P1 (P＜0.05) , and no significant change was found in the parameters mentioned above in P2 and P3 groups (P＞0.05).Conclusion The mechanism by which mechanical ventilation preconditioning decreases ventilator-induced lung injury may be related to inhibition of the expression of ROCK1 in lung tissues of rats.
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Objective To investigate the effects of dexmedetomidine on inflammatory responses in brain tissues of the patients undergoing carotid endarterectomy.Methods A total of 40 ASA physical status Ⅱ or Ⅲ patients,aged 65-80 yr,scheduled for elective unilateral carotid endarterectomy under general anesthesia,were randomly divided into 2 groups (n =20 each) using a random number table:dexmedetomidine group (group Dex) and control group (group C).In group Dex,dexmedetomidine 0.03 μg · kg-1 · min-1 was infused over 10 min before induction of anesthesia,and after tracheal intubation dexmedetomidine was then infused at a rate of 0.3 μg · kg-1 · min-1 until 30 min before the end of operation.The equal volume of normal saline was given in group C.At 20 min before induction of anesthesia (T0),10 min after induction of anesthesia (T1),15 min after carotid artery clamping (T2),15 min after carotid artery unclamping (T3),and at 6 and 24 h after operation (T4,5),blood samples were drawn from the ispilateral jugular bulb for determination of serum concentrations of malondialdehyde (MDA) (by TBA) and S100B,tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (by ELISA).Results Compared with group C,the serum S100B concentrations were significantly decreased at T3-5,the serum TNF-α and IL-6 concentrations were decreased at T2.5,and the serum MDA concentration was decreased at T3 in group Dex.Conclusion Dexmedetomidine can reduce the brain damage through mitigating inflammatory responses in brain tissues of the patients undergoing carotid endarterectomy.
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Objective To systematically review the efficacy of dexmedetomidine and fentanyl-class drugs for induction in awake intubation patients.Methods We searched the PubMed,Embase, Cochrane library,Wanfang Database,CNKI,VIP and China Biology Medicine (CBM)for all ran-domized controlled trials (RCTs)about the efficacy of dexmedetomidine versus drugs of fentanyl class (fentanyl,sufentanil,remifentanil)for induction in awake intubation patients.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.Meta-analysis was con-ducted using the Cochrane Collaboration's RevMan 5.0 software.Results Ten RCTs involving 400 patients were included in our Meta-analysis.The results of meta-analysis showed that the ramsay se-dation scores in awake intubation patients was higher in group dexmedetomidine than that of group fentanyl-class drugs (P<0.05).Compared with group fentanyl-class drugs,the incidence of compli-cations such as hypertension,respiratory depression,bucking and post-surgical memory in the group dexmedetomidine was lower (P<0.05).Conclusion The efficacy of dexmedetomidine is better than that fentanyl-class drugs for induction in awake intubation patients.
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Objective To evaluate the effects of mechanical ventilation preconditioning on ventilatorinduced lung injury in rats.Methods Forty-eight healthy male Sprague-Dawley rats,weighing 250-300 g,were randomly assigned into 6 groups (n =8 each) using a random number table:control group (group C),normal ventilation group (group N),mechanical ventilation with large tidal volume (VT) group (group L) and mechanical ventilation preconditioning group (group P).The animals were anesthetized with intraperitoneal 2 ％ pentobarbital sodium 0.2 ml/100 g.Tracheal intubation was performed.In group C,the animals kept spontaneous breathing after intubation.In group N,the animals were mechanically ventilated for 3 h with the VT of 8-10 ml/kg.The animals were mechanically ventilated for 3 h with the VT of 40 ml/kg in group L.In group P,the animals were mechanically ventilated for 30 min with the VT of 6 ml/kg,and then were mechanically ventilated for 3 h with the VT of 40 ml/kg (RR 40 bpm,I:E =l:l,PET CO2 35-45 mmHg).The animals were sacrificed at the end of ventilation,and the lungs were removed for measurement of wet to dry lung weight ratio (W/D ratio) and cell apoptosis and for microscopic examination of the pathological changes of the lung and the lung injury was scored.The apoptosis.index was calculated.Results Compared with group C,the lung injury score,W/D ratio,and apoptosis index were significantly increased in L and P groups,and no significant change was found in the parameters mentioned above in group N.Compared with group L,the lung injury score,W/D ratio,and apoptosis index were significantly decreased in group P.Conclusion Mechanical ventilation preconditioning can reduce ventilator-induced lung injury in rats.
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Objective To evaluate the effects of dexmedetomidine on postoperative cognitive function in the aged patients undergoing carotid endarterectomy.Methods Forty patients,aged 65-80 yr,of ASA physical status Ⅱ or Ⅲ,scheduled for elective carotid endarterectomy,were randomly divided into 2 groups (n =20 each):control group (group C) and dexmedetomidine group (group DEX).Anesthesia was induced with midazolam,etomidate,fentanyl and rocuronium.The patients were tracheally intubated.In group DEX,a loading dose of dexmedetomidine 0.03 μg· kg-1 ·min-1 was infused intravenously for 10 min starting from the time point before induction,and dexmedetomidine 0.30μg· kg-1 ·min-1 was infused until 30 min before the end of operation starting from the end of intubation.The equal volume of normal saline was given instead of dexmedetomidine in group C.At 1 day before operation (To) and 6 and 24 h after operation (T1.2),venous blood samples were collected for determination of serum brain-derived neurotrophic factor (BDNF) concentrations.The cognitive function of the patients was assessed using Mini-Mental State Examination (MMSE) at To,T2,and 48 h,72 h,7days and 1 month after operation (T3-6).Results Compared with the baseline value at T0,the serum BDNFconcentrations were significantly increased at T1 in the two groups,MMSE scores were decreased at T2,3 in groupC,and MMSE scores were decreased,and the serum BDNF concentrations were increased at T2 in group DEX.Compared with group C,the MMSE scores were significantly increased at T3.4,the serum BDNF concentrations were increased at T2,and no significant change was found in MMSE scores at T5.6 in group DEX.Conclusion Dexmedetomidine is helpful in improving postoperative cognitive function and in promoting the recovery of postoperative cognitive function,and the mechanism may be related to enhanced production of endogenous BDNF in the aged patients undergoing carotid endarterectomy.