Effect of dexmedetomidine on JAK2/STAT3 signaling pathway in lung tissues in a rat model of cardiopulmonary bypass / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in lung tissues in a rat model of cardiopulmonary bypass (CPB).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, weighing 320-350 g, aged 12-16 weeks, were randomly divided into sham operation group (group S), CBP group, and dexmedetomidine group (group Dex), with 8 rats in each group.In group Dex, dexmedetomidine was intravenously infused in a dose of 5 μg/kg starting from 15 min before CPB followed by infusion of 5 μg·kg -1·h -1 during CPB.Blood samples were collected at 2 h after the end of CPB for blood gas analysis, and oxygenation index (OI) and respiratory index (RI) were calculated.Then the rats were sacrificed by bloodletting.The lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)(by enzyme-linked immunosorbent assay), and expression of JAK2, STAT3, phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) (by Western blot). The p-JAK2/JAK2 and p-STAT3/STAT3 ratios were calculated. Results:Compared with group S, the lung injury score, W/D ratio and RI were significantly increased, OI was decreased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were increased in the other two groups ( P<0.05). Compared with group CPB, the lung injury score, W/D ratio and RI were significantly decreased, OI was increased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were decreased in group Dex ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates CPB-induced lung injury may be related to inhibiting JAK2/STAT3 signaling pathway and reducing inflammatory responses in lung tissues of rats.

Development of cerebral anoxia during controlled hypotension with nicardipine or urapidil after ca-rotid endarterectomy / 中华麻醉学杂志

Objective To evaluate the development of cerebral anoxia during controlled hypoten-sion with nicardipine or urapidil after carotid endarterectomy in patients. Methods Forty-four patients of either sex, aged 48-64 yr, scheduled for elective carotid endarterectomy under general anesthesia, requi-ring controlled hypotension after operation, were divided into nicardipine group ( group N ) and urapidil group ( group U) using a random number table method, with 22 patients in each group. Nicardipine at 2. 5μg·kg-1 ·min-1 was intravenously infused in group N, and urapidil 2μg·kg-1 ·min-1 was intravenously infused in group U. After systolic blood pressure was decreased to 130-140 mmHg, the consumption of nicardipine was adjusted to 0. 2 - 0. 5 μg·kg-1 ·min-1 and the consumption of urapidil to 1-2μg·kg-1 ·min-1 in group N and group U, respectively, to maintain systolic pressure at 130-140 mmHg. Heart rate ( HR) , cardiac index ( CI) , bispectral index ( BIS) value, regional cerebral oxygen saturation (rSO2) and end-tidal pressure of carbon dioxide (PETCO2) were recorded after entering the operating room ( baseline) , at the beginning of controlled hypotension ( T1 ) , and at 5, 10, 20, 30, 60 and 120 min af-ter systolic blood pressure was decreased to the target hypotension ( T2-7 ) . Development of cerebral anoxia( the relative decrease in rSO2>12％ of the baseline value) was recorded in controlled hypotension period. Results Compared with the value at T1 , the HR at T2,3 and CI at T3-7 were significantly increased ( P<0. 05), and no significant change was found in rSO2, PETCO2 or BIS value at the other time points in group N (P>0. 05), and rSO2 was significantly decreased at T3-7 (P<0. 05), and no significant change was found in HR, CI, PETCO2 or BIS value at the other time points in group U (P>0. 05). Compared with group N, the HR at T2,3, CI at T3-7 and rSO2 at T3-7 were significantly decreased in group U (P<0. 05). The incidence of cerebral anoxia was significantly higher in group U than in group N ( P<0. 05) . Conclu-sion Controlled hypotension with nicardipine is recommended after carotid endarterectomy in order to avoid the development of cerebral anoxia in the patients.

Effect of α7nAChR agonists on acute lung injury caused by cardiopulmonary bypass in rats / 中华麻醉学杂志

Objective To evaluate the effect of α7 nicotinic acetylcholine receptor (α7nAChR)agonists on lung injury caused by cardiopulmonary bypass (CPB) in rats.Methods Eighteen healthy clean-grade adult male Sprague-Dawley rats,weighing 350-400 g,were divided into 3 groups (n =6 each)using a random number table method:sham operation group (group S),CPB group and α7nAChR agonist PHA568487 group (group PHA).The rats underwent no CPB and were mechanically ventilated for 60 min in group S.PHA568487 0.8 mg/kg (diluted to 2 ml in normal saline) was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group PHA.Normal saline 2 ml was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group CPB.Blood samples were collected from the internal jugular vein for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathologic changes and for determination of wet/dry weight ratio (W/D ratio) and matrix metalloproteinase-9 (MMP-9) expression (by Western blot).Results Compared with group S,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly increased,and the expression of MMP-9 was up-regulated in CPB and PHA groups (P＜0.05).Compared with group CPB,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly decreased,the expression of MMP-9 was down-regulated (P＜0.05),and the pathological changes of lung tissues were significantly attenuated in group PHA (P＜0.05).Conclusion α7nAChR agonists can reduce the acute lung injury caused by CPB in rats,and the mechanism may be related to down-regulating MMP-9 expression and inhibiting systemic inflammatory responses.

Effect of hemorrhagic shock factor on pharmacokinetics of rocuronium in pigs / 中华麻醉学杂志

Objective To evaluate the effect of hemorrhagic shock factor on the pharmacokinetics of rocuronium in pigs.Methods Sixteen pathogen-free Bama miniature pigs of both sexes,aged 3-5 months,weighing 22-25 kg,were divided into 2 groups (n=8 each) using a random number table:control group (group C) and hemorrhagic shock group (group HS).In group C,rocuronium 3.78 mg/kg was injected via the auricular vein.In group HS,the animals were subjected to volume-controlled hemorrhage,about 40％ of blood volume was withdrawn from the left femoral artery over 15 min (30 ml/kg),and rocuronium 3.78 mg/kg was injected via the auricular vein after the model was successfully established.At 0,2,4,7,10,15,20,30,60,120,180,240,300,360 and 420 min after rocuronium injection,blood samples were collected from the internal jugular vein for determination of the plasma concentration of rocuronium by high-performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters of rocuronium were calculated.Results Compared with group C,the plasma concentration of rocuronium was significantly increased at 20 and 60-420 min after rocuronium injection,the elimination half-life and mean residence time were prolonged,and the plasma effect-site equilibration rate constant was decreased in group HS (P＜0.05).There was no significant difference in the maximal concentration and area under the concentration-time curve between the two groups (P＞ 0.05).Conclusion The elimination of rocuronium is slower in a pig model of hemorrhagic shock.

Effect of sevoflurane on activation of NF-κB during brain injury induced by hemorrhagic shock in pigs / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on activation of nuclear factor kappa B (NF-κB) during brain injury induced by hemorrhagic shock (HS) in pigs.Methods Thirty-two adult male Bama miniature pigs,aged 6 months,weighing 22-25 kg,were divided into 4 groups (n=8 each) using a random number table:sham operation group (group Sham),HS group,sevoflurane preconditioning group (group Sev-Pre) and sevoflurane postconditioning group (group Sev-Post).The animals were anesthetized,and tracheostomized and mechanically ventilated.In group Sham,the bilateral femoral arteries and internal jugular veins were only cannulated.HS was induced by removing 40％ of blood volume within 15 min (30 ml/kg) via the right femoral artery and maintaining at this level for 1 h before resuscitation in HS,Sev-Pre and Sev-Post groups.In group Sev-Pre,2％ sevoflurane was inhaled for 30 min,and then HS was induced.In group Sev-Post,2％ sevoflurane was inhaled for 30 min starting from the time point immediately after HS was induced.Immediately before establishment of the model and at 30,60,90,120,180 and 240 min of HS (T1-6),blood samples from the jugular vein were collected for determination of serum interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) concentrations by enzymelinked immunosorbent assay.At 4 h of HS,the rats were sacrificed,and brains were removed for microscopic examination of hippocampal CA1 region (using haematoxylin and eosin staining) and for determination of the expression of NF-κB in nucleoprotein (by Western blot).Results Compared with group Sham,the concentrations of serum IL-1β and TNF-α were significantly increased at T2-6,and the expression of NF-κB in nucleoprotein in hippocampal CA1 region was up-regulated in HS,Sev-Pre and Sev-Post groups (P＜0.05).Compared with group HS,the concentrations of serum IL-1β and TNF-α were significantly decreased at T3-6,and the expression of NF-κB in nucleoprotein in hippocampal CA1 region was down-regulated in Sev-Pre and Sev-Post groups (P＜0.05).There were no significant differences between group SevPre and group Sev-Post in concentrations of serum IL-1β and TNF-α and expression of NF-κB in nucleoprotein in hippocampal CA1 region (P＞0.05).The pathologic changes were significantly attenuated in SevPre and Sev-Post groups as compared with group HS.Conclusion The mechanism by which sevoflurane attenuates brain injury induced by HS may be related to inhibition of NF-κB activation and reduction of inflammatory responses in pigs.

Effect of environmental hypothermia exposure on hemodynamics and oxygen metabolism during general anesthesia in a pig model of hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the effect of environmental hypothermia exposure on hemodynamics and oxygen metabolism during general anesthesia in a pig model of hemorrhagic shock.Methods Twelve pathogen-free Bama miniature pigs of both sexes,weighing 20-24 kg,were divided into 2 groups (n=6 each) using a random number table:room temperature group (group RT) and environmental hypothermia group (group EH).The animals inhaled 2％ isoflurane for maintenance of anesthesia.The pigs were placed at room temperature (20-22℃) and at low temperature (-10 ℃) in group RT and group EH,respectively.Hemorrhagic shock was induced by withdrawing blood from the right femoral artery within 20 min (30 ml/kg).Before withdrawing blood (T1),immediately after the end of withdrawing blood (T2),and at 1,2,3,4 and 5 h of shock (T3-7),heart rate,mean arterial pressure,mean pulmonary artery pressure,cardiac index and systemic vascular resistance index were recorded.Blood samples were collected from the right femoral artery and internal jugular vein for blood gas analysis,and lactic acid concentrations,hemoglobin,arterial oxygen partial pressure,arterial oxygen saturation,and mixed venous oxygen saturation were recorded.Oxygen delivery index,oxygen consumption index and O2 extraction rate were calculated.Results Compared with group RT,heart rate at T3-7,cardiac index and oxygen delivery index at T5-7,oxygen consumption index at T1-7,O2 extraction rate at T2-6,and lactic acid concentrations at T5-7 were significantly decreased,and mean arterial pressure at T4,5,mean pulmonary artery pressure at T4-7,systemic vascular resistance index at T3-7,and mixed venous oxygen saturation at T2-6 were increased in group EH (P＜0.05).Conclusion Environmental hypothermia exposure inhibits cardiac compensatory responses,increases the peripheral vascular resistance,and aggravates oxygen dysmetabolism during general anesthesia in a pig model of hemorrhagic shock.

Effect of hypothermia on pharmacokinetics of rocuronium in pigs with hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the effect of hypothermia on the pharmacokinetics of rocuronium in the pigs with hemorrhagic shock.Methods Thirty-two Bama mini pigs of both sexes,aged 4-6 months,weighing 22-25 kg,were randomly divided into 4 groups (n=8 each) using a random number table:normal temperature control group (group NC),normal temperature+hemorrhagic shock group (group NH),hypothermia control group (group HC),and hypothermia+hemorrhagic shock group (group HH).NC and NH groups were put in the normal temperature environment,and HC and HH groups were put in a freezer at-15 ℃.In NC and HC groups,rocuronium 3.78 mg/kg was injected via the auricular vein after the animals were awake.In NH and HH groups,hemorrhagic shock was then induced by removing 40％ of blood volume from the right femoral artery at a constant speed within 15 min (30 ml/kg),and rocuronium 3.78 mg/kg was injected via the auricular vein at 30 min after the model was successfully established.At 0 (T0),2 (T1),4 (T2),7 (T3),10 (T4),15 (T5),20 (T6),30 (T7),60 (T8),120 (T9),180 (T10),240 (T11) and 300 min (T12) after rocuronium injection,blood samples were collected from the internal jugular vein for determination of the blood concentration of rocuronium by high performance liquid chromatography-tandem mass spectrometry method.The maximum concentration (Cmax),elimination half-life (t1/2),plasma effect-site equilibration rate content (Ke0),area under concentration curve,and mean residence time (MRT) of rocuronium were calculated.Results Compared with group NC,the blood concentration of rocuronium was significantly decreased at T5-T12 in group NH,the blood concentration of rocuronium was significantly increased at T5-T12 in group HC,and t1/2 was significantly prolonged,Ke0 was decreased,and MRT was prolonged in NH and HC groups (P＜0.05 or 0.01).Compared with group HC,the blood concentration of rocuronium was significantly increased at T4-T12,t1/2 was prolonged,Ke0 was decreased,and MRT was prolonged in group HH (P＜0.05).Compared with group NH,the blood concentration of rocuronium was significantly increased at T5-T11,t1/2 was prolonged,Ke0 was decreased,and MRT was prolonged in group HH (P＜ 0.05).Conclusion Hypothermia can reduce the pharmacokinetics of rocuronium in the pigs with hemorrhagic shock.

Direct renin inhibitor aliskiren increases AQP2 expression in renal collecting ducts and improves urinary concentration defect in NDI / 中国病理生理杂志

AIM:The direct renin inhibitor aliskiren displays antihypertensive and antialbuminuric effects in humans and in animal models . Emerging evidence has shown that aliskiren localizes and persists in medullary collecting ducts even after treatment was discontinued . The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression and improves urinary concen -trating defect induced by lithium .METHODS:The mice were either fed with normal chow or LiCl diet (40 mmol/kg dry food per day for first 4 days and 20 mmol/kg dry food per day for last 3 days ) for seven days .Some mice were intraperitoneally injected aliskiren ( 50 mg/kg BW per day in saline ) .RESULTS:Mice injected aliskiren developed decreased urine output and increased urine osmolal -ity when compared with controls .Aliskiren significantly increased protein abundance of AQP 2 and phosphorylated-S256 AQP2 in the kidney inner medulla .Immunohistochemistry and immunofluoresence showed increased apical and intracellular labeling of AQP 2 and pS256-AQP2 in collecting duct principal cells of kidneys in mice treated with aliskiren .Aliskiren treatment prevented urinary concen-trating defect in lithium-treated mice , and improved the downregulation of AQP 2 and pS256-AQP2 protein abundance in inner medulla of the kidney .In primary cultured rat inner medulla collecting duct cells , aliskiren dramatically increased AQP 2 protein abundance which was significantly inhibited either by PKA inhibitor H 89 or by adenylyl cyclase inhibitor MDL 12330, indicating an involvement of the cAMP signalling pathway in mediating aliskiren-induced increased AQP 2 expression .CONCLUSION: The direct renin inhibitor aliskiren upregulates AQP 2 protein expression in inner medullary collecting duct principal cells and prevents lithium -induced nephro-genic diabetes insipidus ( NDI) likely via PKA-cAMP pathways .

Effect of sevoflurane preconditioning on brain injury induced by cardiopulmonary bypass in rats / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane preconditioning on brain injury induced by cardiopulmonary bypass (CPB) in rats.Methods Forty adult male Sprague-Dawley rats,aged 6-8 months,weighing 350-450 g,were randomly divided into 5 groups (n=8 each) using a random number table:sham operation group (S group),CPB group,and preconditioning with different concentrations of sevoflurane groups (SP1,SP2 and SP3 groups).In SP1,SP2 and SP3 groups,sevoflurane with the final concentrations of 1.2％,2.4％ and 3.6％,respectively,was inhaled for 1 h,and then CPB was started.After sevoflurane preconditioning and before CPB (T0),at 30 min of CPB (T1),at the end of CPB (T2),and at 1,2 and 3 h after termination of CPB (T3-5),venous blood samples were collected from the right internal jugular vein for determination of serum S100-β protein concentrations by enzyme-linked immunosorbent assay.Rats were sacrificcd at T5,and hippocampi were isolated for determination of neuronal apoptosis (by TUNEL) and NF-κB p65 expression (by immunohistochemistry).Results Compared with group S,the concentration of serum S100-β protein was significantly increased at T1-5,the number of apoptotic neurons was significantly increased,and the expression of NF-κB p65 was significantly up-regulated in CPB,SP1,SP2 and SP3 groups (P＜0.05).Compared with group CPB,the serum S100-β protein concentration was significantly decreased at T1-5,the number of apoptotic neurons was significantly decreased,and the expression of NF-κB p65 was significantly down-regulated in SP1,SP2 and SP3 groups (P＜ 0.05).Compared with group SP1,the serum S100-β protein concentration was significantly decreased at T1-5,the number of apoptotic neurons was significantly decreased,and the expression of NF-κB p65 was significantly down-regulated in SP2 and SP3 groups (P＜0.05).Compared with group SP2,the serum S100-β protein concentration was significantly decreased at T1-5,the number of apoptotic neurons was significantly decreased,and the expression of NF-κB p65 was significantly downregulated in group SP3 (P＜0.05).Conclusion Sevoflurane preconditioning can attenuate CPB-induced brain injury probably by inhibiting activation of NF-κB in hippocampal neurons of rats.

Effect of sevoflurane on liver injury in pigs with hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on liver injury in a pig model of hemorrhagic shock.Methods Twenty-four Bama miniature pigs of both sexes,weighing 20-25 kg,aged 3-5 months,were equally randomized into 3 groups using a random number table:sham operation group (group S);hemorrhagic shock group (group HS);sevoflurane group (group Sev).Hemorrhagic shock was induced by withdrawing 40％ of blood volume from the right femoral artery within 15 min (30 ml/kg) in HS and Sev groups.The animals inhaled 2％ sevoflurane for 30 min after establishment of the model in group Sev.Before hemorrhagic shock (T0),and at 30,60,90,120,180 and 240 min after hemorrhagic shock (T1-6),blood samples were collected from the femoral artery for determination of plasma alaninc aminotransferase (ALT) and betaine-homocysteine S-methyltransferase (BHMT) concentrations (by enzymelinked immunosorbent assay).After blood sampling at T6,the animals were sacrificed,and the right lobes of livers were removed for examination of the pathological changes with light microscope.Results Compared with group S,the plasma ALT concentrations were significantly increased at T4-6,the plasma BHMT concentrations were significantly increased at T3-6 (P＜0.05),and significant liver pathological changes were observed in HS and Sev groups.Compared with group HS,the plasma ALT concentrations were significantly decreased at T4-6,the plasma BHMT concentrations were significantly decreased at T3-6 (P＜0.05),and the liver pathological changes were significantly attenuated in group Sev.Conclusion Sevoflurane can mitigate liver injury in a pig model of hemorrhagic shock.

Effect of dexmedetomidine on acute kidney injury in endotoxemic rats / 中华麻醉学杂志

Objective To investigate the effect of dexmedetomidine on acute kidney injury in endotoxemic rats.Methods Thirty adult male Sprague-Dawley rats,aged 4-6 months,weighing 180-220 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group (group C),lipopolysaccharide group (group L),and dexmedetomidine (group D).Lipopolysaccharide (LPS) 5 mg/kg was injected slowly into the femoral vein to establish the model of endotoxemic in rats anesthetized with chloral hydrate.In group D,after LPS injection,a loading dose of dexmedetomidine 7 μg/kg was injected intravenously,and 15 min later dexmedetomidine was infused for 6 h at 5 μg · kg-1 · h-1,while the equal volume of normal saline was given in L and C groups.At 6 h after the end of LPS administration,blood samples were collected from the femoral vein for determination of serum creatinine (Cr),blood urea nitrogen (BUN),tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations.At 24 h after the end of LPS administration,the animals were sacrificed and kidneys were removed for microscopic examination and for determination of the expression of tight junction proteins ZO-1 and occludin in renal tissues by Western blot.Results Compared with group C,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly increased,and the expression of ZO-1 and occluding was down-regulated in L and D groups.Compared with group L,the serum Cr,BUN,TNF-α and IL-6 concentrations were significantly decreased,the expression of ZO-1 and occluding was up-regulated,and the pathological changes of kidneys were mitigated in D group.Conclusion Dexmedetomidine can alleviate acute kidney injury in endotoxemic rats.

Effect of dexmedetomidine on acute liver injury in rats with endotoxemia / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on acute liver injury in rats with endotoxemia.Methods Eighteen adult male Sprague-Dawley rats, aged 3-4 months, weighing 250-300 g, were randomly divided into 3 groups (n=6 each) using a random number table: control group (group C), endotoxin group (group E), and dexmedetomidine group (group D).In E and D groups, lipopo-lysaccharide 5 mg/kg was injected via the femoral vein of rats anesthetized with chloral hydrate.In group D, dexmedetomidine was infused with a 7 μg/kg loading bolus over 15 min after injection of lipopolysaccharide, followed by a 6 h continuous infusion of 5 μg · kg-1 · h-1.The equal volume of normal saline was given instead in E and C groups.After the end of administration, blood samples from the femoral vein were drawn for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) concentrations in serum (by using enzyme-linked immunosorbent assay), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum (using the International Federation of Clinical Chemistry and Laboratory Medicine reference procedures).Liver specimens were obtained for examination of pathologic changes with electron microscope.Results Compared with group C, the serum ALT and AST activities and TNF-α and IL-lβ concentrations were significantly increased in E and D groups.Compared with group E, the serum ALT and AST activities and TNF-α and IL-1β concentrations were significantly decreased in group D.The pathologic changes of livers were obvious in group E, and were significantly reduced in group D compared with group E.Conclusion Dexmedetomidine can alleviate acute liver injury in rats with endotoxemia, and the underlying mechanism is associated with inhibition of systemic inflammatory responses.

Effect of sevoflurane on brain injury in a pig model of hemorrhagic shock in hypothermia environ-ment / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on brain injury in a pig model of hem?orrhagic shock in hypothermia environment. Methods Twenty?four Bama miniature pigs, weighing 21-25 kg, aged 3-5 months, were equally randomized into 3 groups using a random number table: sham opera?tion group (group Sham);hemorrhagic shock (group HS); sevoflurane group (group Sev). The animals were anesthetized, tracheostomized and mechanically ventilated. Bilateral femoral arteries were cannulated for continuous mean arterial pressure, and heart rate monitoring, blood?letting and blood sampling. A cath?eter was inserted into the right internal jugular vein for body temperature monitoring. After the animals were awake, they were placed in an environment at-15℃. Hemorrhagic shock was induced by withdrawing 40%of blood volume from the right femoral artery within 15 min ( 30 ml∕kg) in HS and Sev groups. The animals inhaled 2% sevoflurane for 30 min after establishment of the model in group Sev. Before hemorrhagic shock, and at 30, 60, 90, 120, 180 and 240 h after hemorrhagic shock ( T0?6 ) , blood samples were collected from the femoral artery for determination of plasma tumor necrosis factor?alpha ( TNF?α) , interleukin?6(IL?6), nuclear factor kappa B (NF?κB), S100β protein and neuron?specific enolase (NSE) concentra?tions. After blood sampling at T6 , the animals were sacrificed, and brains were removed for microscopic examination of pathological changes, and for determination of Toll?like receptor 4 ( TLR4) expression by Western blot. Results Compared with group Sham, the plasma NSE, S100β protein, TNF?α, IL?6 and NF?κB concentrations were significantly increased at T2?6 , and TLR4 expression was up?regulated at T6 in HS and Sev groups ( P<0?05) . Compared with group HS, the plasma NSE, and S100βprotein concentra?tions were significantly decreased at T4?6 , the plasma TNF?α, IL?6 and NF?κB concentrations were de?creased at T2?6, and TLR4 expression was down?regulated at T6 (P<0?05), and the pathological changes were significantly attenuated in group Sev. Conclusion Sevoflurane can mitigate brain injury in a pig mod?el of hemorrhagic shock in hypothermia environment, and the mechanism may be related to inhibited TLR4∕NF?κB signaling pathway and attenuated inflammatory responses.

Effect of sevoflurane on expression of aquaporin 8 in intestinal mucosa in a pig model of hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on the expression of aquaporin 8 (AQP8) in the intestinal mucosa in a pig model of hemorrhagic shock.Methods Twenty-four Bama miniature pigs of both sexes, weighing 22-25 kg, were randomly divided into 3 equal groups using a random number table: sham operation group (group S), hemorrhagic shock group (group HS) and sevoflurane group (group PS).The femoral artery and jugular vein were cannulated for blood pressure monitoring, blood-letting, and blood sampling in anesthetized pigs.Hemorrhagic shock was induced by withdrawing blood from the right femoral artery.Hemorrhagic shock was induced after cannulation in group HS.In group PS, 2％ sevoflurane was inhaled for 30 min after the model of hemorrhagic shock was successfully established.Before anesthesia, and at 0.5, 1, 1.5, 2, 3 and 4 h after hemorrhagic shock, blood samples were collected from the jugular vein for determination of serum D-lactic acid and intestinal fatty acid-binding protein (I-FABP) concentrations.The animals were sacrificed at 4 h after hemorrhagic shock, and the intestinal specimens were obtained for microscopic examination and for determination of AQP8 expression in the intestinal mucosa (by enzyme-linked immunosorbent assay).The intestinal water content was calculated.Results Compared with group S, the serum D-lactic acid and I-FABP concentrations, AQP8 expression, and intestinal water content were significantly increased in HS and PS groups (P＜0.05).Compared with group HS, the serum D-lactic acid and I-FABP concentrations, AQP8 expression, and intestinal water content were significantly decreased in group PS (P＜0.05).The pathological changes of intestinal tissues were significantly reduced in group PS as compared with group HS.Conclusion Sevoflurane can decrease the intestinal mucosal edema through inhibiting AQP8 expression, thus reducing hemorrhagic shockinduced damage to the intestinal mucosa in pigs.

Effectof monosialoganglioside on hippocampal Akt/GSK-3β signaling pathway in rats undergoing cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effect of monosialoganglioside (GM-1) on hippocampal protein kinase B (Akt) /glycogen synthase kinase 3β (GSK-3β) signaling pathway in the rats undergoing cardiopulmonary bypass (CPB).Methods Eighteen healthy male Sprague-Dawley rats, aged 6 months, weighing 400-500 g, were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C), CPB group and GM-1 group.GM-1 20 mg/kg was added to the priming solution in group GM-1, while the equal volume of normal saline was given in group CPB.At 3 h after termination of CPB, blood samples were taken from the jugular vein for determination of plasma neuron-specific enolase (NSE) and S-100β protein concentrations using enzyme-linked immunosorbent assay.After blood sampling, the rats were sacrificed, and the hippocampi were isolated for microscopic examination of the ultrastructure of the hippocampal neurons (with electron microscope), and for detection of neuronal apoptosis (with light microscope) and phosphorylation of Akt and GSK-3β (by Western blot).Results Compared with group C, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly increased in CPB and GM-1 groups, the phosphorylation of Akt and GSK-3β was decreased in group CPB, and the phosphorylation of Akt and GSK-3β was increased in group GM-1 (P＜0.05).Compared with group CPB, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly decreased, the phosphorylation of Akt and GSK-3β was increased (P＜0.05), and the pathological changes were reduced in group GM-1.Conclusion GM-1 can reduce apoptosis in hippocampal neurons through activating Akt/GSK-3β signaling pathway, thus mitigating CPB-induced brain injury in rats.

Effect of sevoflurane on brain injury in pigs with hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on brain injury in pigs with hemorrhagic shock (HS).Methods Twenty-four adult male Bama miniature pigs, aged 6 months, weighing 22-25 kg, were equally and randomly divided into 3 groups using a random number table: sham operation group (group Sham) , group HS, and sevoflurane group (S group).In group Sham, the bilateral femoral arteries and internal jugular vein were only punctured.The animals were anesthetized with iv propofol 3.0 mg/kg, tracheostomized and mechanically ventilated.The right femoral artery was cannulated for blood-letting.HS was induced by blood-letting (40％ blood volume within 15 min), and it was then maintained for 1 h after the end of blood-letting to induce brain injury.In group S, 2％ sevoflurane was inhaled for 30 min after successful establishment of the model.Immediately before establishment of the model (T0) , and at 30, 60,90, 120, 180 and 240 min after HS (T1-6) , blood samples were collected from the internal jugular vein for determination of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) concentrations in serum (by enzyme-linked immunosorbent assay), and neuron-specific enolase (NSE) and S-100β protein concentrations in serum (using double antibody sandwich method).Results Compared with group Sham, the serum IL-1β, TNF-α, NSE and S-100β protein concentrations were significantly increased at T2-6 in HS and S groups (P＜0.05).Compared with group HS, the serum IL-1β, TNF-α, NSE and S-100β protein concentrations were significantly decreased at T3-6 in group S (P＜ 0.05).Conclusion Sevoflurane can mitigate brain injury in pigs with HS, and the mechanism is associated with inhibition of inflammatory responses.

Changes in expression of aquaporin-8 in intestinal mucosa in pigs with hemorrhagic shock / 中华麻醉学杂志

Objective To evaluate the changes in the expression of aquaporin-8 (AQP8) in intestinal mucosa in pigs with hemorrhagic shock.Methods Sixteen Bama miniature pigs,weighing 22-25 kg,were equally and randomly divided into sham operation group (group S) and hemorrhagic shock group (group HS).The animals were fasted for 8 h before operation.The animals were anesthetized with propofol 3 mg/kg injected via the auricular vein,and tracheostomized and mechanically ventilated.In group S,the femoral artery and internal jugular vein were only cannulated.In group HS,the femoral artery and internal jugular vein were cannulated for blood pressure and mean arterial pressure monitoring and blood sampling.Hemorrhagic shock was then induced by removing 40 percent of blood volume over 15 min.Before anesthesia (T0),and at 30 min and 1.0,1.5,2.0,3.0 and 4.0 h after the end of blood-letting (T1.6),blood samples were collected for determination of serum D-lactate and intestinal fatty acid binding protein (I-FABP) concentrations.After blood sampling at T6,the pigs were sacrificed,and intestinal specimens were obtained for microscopic examination and for determination of AQP8 cotent in intestinal mucosa (by ELISA).The water content of intestines was calculated by wet/dry weight ratio.Results Compared with group S,the serum D-lactate concentrations at T2-6,I-FABP concentrations at T1-6,and water content of intestines were significantly increased,and the cotent of AQP8 was up-regulated at T6 in group HS.No changes were found in the intestinal mucosa in group S.In group HS,severe damage to the intestinal mucosa was found,and bleeding,inflammatory cell infiltration,and epithelial cell necrosis were observed.Conclusion The mechanism of hemorrhagic shock-caused damage to intestines is related to up-regulated expression of AQP8 in intestinal mucosa in pigs.

Effect of sevoflurane on myocardial injury induced by hemorrhagic shock and resuscitation in pigs / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on myocardial injury induced by hemorrhagic shock and resuscitation (HS/R) in pigs.Methods Twenty-four Bama miniature pigs (12 males, 12 females) , weighing 20-25 kg, aged 3-5 months, were randomly divided into 3 groups (n=8 each) using a random number table: sham operation group (group S) , HS/R group and sevoflurane group (group Sev).The left and right femoral arteries and right femoral vein were cannulated for blood pressure monitoring, blood-letting, blood sampling and fluid infusion.HS/R was induced by blood-letting maintaining for 1 h, followed by resuscitation with autologous blood reinfusion and infusion of lactated Ringer's solution 2 times the volume of the blood withdrawn.The pigs in group Sev were exposed to 2％ sevoflurane for 30 min before resuscitation.After cannulation, at 30 min after hemorrhagic shock, before resuscitation, and at 30 min, and 1.5, 2.5 and 3.5 h after resuscitation, blood samples were collected from the femoral artery for determination of creatine kinase-MB (CK-MB) activity and cardiac troponin Ⅰ (cTnI) concentration in serum using an automatic biochemical analyzer.Myocardial specimens were obtained at 3.5 h after resuscitation for detection of tumor necrosis factor-alpha (TNF-ot) and interleukin-6 (IL-6) contents (by ELISA) , and phosphor-signal transducer and activator of transcription 1 (p-STAT1) expression (by Western blot), and for examination of the pathological changes (with light microscope).Results Compared with S group , the CK-MB activity and cTnI concentration in serum and contents of TNF-α and IL-6 were significantly increased, and the expression of p-STAT1 was up-regulated in HS/R and Sev groups (P＜0.05).Compared with HS/R group, the CK-MB activity and cTnI concentration in serum and contents of TNF-α and IL-6 were significantly decreased, and the expression of p-STAT1 was downregulated (P＜0.05) , and the pathological changes of myocardia were alleviated in Sev group.Conclusion Sevoflurane can alleviate HS/R-induced damage to myocardia of pigs, and inhibited STAT1 activity and attenuated inflammatory responses in the myocardium are involved in the mechanism.

Effect of dexmedetomidine on lung injury induced by renal ischemia/reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on lung injury induced by renal ischemia/reperfusion (l/R) in rats.Methods Healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were randomized into 4 groups (n =10 each) using a random number table:sham operation group (group S); group I/R; dexmedetomidine pretreatment group (group D1) and dexmedetomidine postconditioning group (group D2).Renal I/R was induced by right nephrectomy and occlusion of the left kidney for 45 min followed by reperfusion in animals anesthetized with intraperitoneal chloral hydrate.In group D1,dexmedetomidine was infused intravenously starting from 30 min before ischemia until beginning of ischemia.In group D2,starting from onset of reperfusion until 30 min of reperfusion,dexmedetomidine was infused intravenously for 10 min at a rate of 1 μg· kg-1 · h-1,and then infused for 20 min at 0.5 μg· kg-1 · h 1.Blood samples were collected at 6 h of reperfusion to determine serum creatinine,blood urea nitrogen,interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) concentrations,and IL-1β,IL-6 and TNF-α concentrations in broncho-alveolar lavage fluid (BALF).Lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results Compared with group S,wet/dry lung weight ratio,serum creatinine and blood urea nitrogen concentrations,and IL-1β,TNF-α and IL-6 concentrations in serum and BALF were significantly increased in the other three groups (P ＜ 0.05).The parameters mentioned above were significantly lower in D1 and D2 groups than in I/R group (P ＜ 0.05).Microscopic examination showed that the pathological changes were significantly attenuated in D1 and D2 groups as compared with I/R group.Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate lung injury induced by renal I/R and inhibition of inflammatory responses is involved in the mechanism.

Effects of different sedation depths of propofol on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effects of different sedation depths of propofol on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty-five ASA physical status Ⅲ or Ⅳ patients of both sexes,aged 26-64 yr,weighing 50-85 kg,scheduled for elective cardiac valve replacement with CPB,were divided into 3 groups according to intraoperative sedation depths (n =15each):30 ≤ bispectral index (BIS) value ＜ 40 (group A) ; 40 ≤ BIS value ≤ 50 (group B) ; 50 ＜ BIS value ≤ 60(group C).Anesthesia was induced with iv injection of lidocaine,midazolam,sulfentanil,etomidate and vecuronium.The patients were tracheally intubated and mechanically ventilated.PET CO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with iv infusion of propofol at a rate of 7,5 and 3 mg· kg-1 · h-1 in A,B and C groups,respectively,intermittent iv boluses of sulfentanil and pipecuronium,and intermittent inhalation of sevoflurane.The infusion rate of propofol was adjusted to maintain the corresponding anesthesic depth in each group.Before CPB (T1),at 30 min of CPB (T2),immediately after termination of CPB (T3) and at 1 h after the end of CPB (T4),blood samples were obtained from the jugular bulb vein and radial artery for determination of plasma S-100β protein concentration and for blood gas analysis,and the arterial to venous blood oxygen content difference (Dj-aO2),cerebral O2 extraction rate (CERO2) and jugular bulb venous to arterial blood lactic acid content difference (Dj-aL) were calculated.Results Compared with group C,the plasma S-100β protein concentrations were significantly decreased,SjvO2 was increased,and Dj-aO2 and CERO2 were decreased at T3-4,and Da-jL was decreased at T3 in groups A and B (P ＜ 0.05).Compared with group B,the plasma S-100β protein concentrations were significantly decreased at T3-4,SjvO2 was increased at T2,Da-jO2 and CERO2 were decreased at T2,and DajL was decreased at T3 in group A (P ＜ 0.05).Conclusion Moderately deepened anesthetic depth of propofol (30≤ BIS value ＜ 40) is helpful in attenuating the brain injury in patients undergoing cardiac valve replacement with CPB.