Objective To investigate the effects of hypertonic saline/hetastarch solution (HHS) on stress hormones and glucose metabolism in hemorrhagic shock rabbit.Methods Fourteen rabbits of both sexes weighing 2.2-2.6 kg were randomly divided into 2 groups : HHS group ( n = 7) and lactated Ringer's solution (LRS) group ( n = 7). The animals were anesthetized with intravenous 20% urethane 5 ml? kg-1 . Femoral artery was cannulated for BP monitoring and femoral vein was cannulated for removal of blood and fluid infusion. Hemorrhagic shock was induced according to Wiggers. MAP was maintained at 45 mm Hg for 45 min. Then the animals in HHS group received HHS 6 ml? kg-1 and those in LRS group LRS 6 ml? kg-1 . Venous blood samples were taken before shock (baseline), during shock before resuscitation, and 30, 60, 120 min after fluid resuscitation for determination of plasma epinephrine, glucagon, insulin and blood glucose concentration. The insulin sensitivity index (ISI) was calculated.Results After resuscitation MAP returned to baseline level in HHS group while in LRS group MAP was still lower than the baseline. The plasma epinephrine, glucagon and blood glucose concentration increased significantly while plasma insulin concentration decreased significantly during shock before fluid resuscitation compared to the baseline in both groups. After fluid resuscitation plasma epinephrine and glucagon concentration decreased significantly and plasma insulin concentration increased significantly in HHS group whereas in LRS group plasma epinephrine, glucagon and insulin concentration kept increasing. The blood glucose level was significantly lower at 60 and 120 min after resuscitation in HHS group than in LRS group. ISI was decreased after resuscitation in both groups but was significantly lower at 60 and 120 min after resuscitation in LRS group than in HHS group.Conclusion Resuscitation with HHS can reduce the stress response and ameliorate the decrease in insulin sensitivity during hemorrhagic shock.

Objective To determine if nitric oxide(NO)is involved in the protective effect of propefolpretreatment(PP)against ischemia-reperfusion injury(I/R).Methods Eighteen male SD rats weighing 250-350 gwere randomly divided into 3 groups(n=6 each):A normal control;B I/R and C PP+I/R.The animals werekilled by a knock on the head.Hearts were immediately removed and passively perfused in a Langendorff apparatusat 37℃ with oxygenated(95% O_2,5% CO_2)Krebs-Hensleit(KH)solution at 90 cm H_20.In group B and C thehearts were subjected to 35 min global ischemia by suspension of perfusion followed by 120 min reperfusion.Ingroup C the hearts were perfused with KH solution containing 50 ?mol?L~(-1) propofol for 10 min followed by 10 minpropefol wash-out before I/R.At the end of reperfusion myocardial specimen was obtained from left ventricle andhomogenized for determination of the activities of total NOS(iNOS+cNOS)aand SOD and expression of iNOS andheme-oxygenase-1(HO-1)and content of NO,The relationship between the NO content and activity and/orexpression of these protein and enzyme were analyzed by correlation analysis.Myocardium was examined with lightand electron microscope.Results The myocardial NO content,tNOS activity and tSOD activity were significantlylower in group B than in group A and C and there was no significant difference in NO content,and activity of tNOSand tSOD between group A and C.The NO content was positively correlated with tNOS and negatively correlatedwith Mn-SOD aetivety and HO-1 expression.Microscopic examination showed severe cell injury or necrosis in groupB but little injury in group C.Conclusion Ischemia and reperfusion decrease activity of tNOS and SOD butincrease HO-1 expression resulting in decrease in NO content.Propofol pretreatment protects the heart from I/Rinjury through increase in NOS and antioxidases(Mn-SOD,HO-1).

Objective There is still a concern that epidural labor analgesia could affect uterinecontraction.The purpose of this study was to investigate the effect of epidural labor analgesia on uterinecontraction.Methods Forty ASA Ⅰ-Ⅱ primiparous women aged 20-30 yr at full term in normal uncomplicateddelivery were enrolled in this study.They were taller than 1.5 m and weighed less than 100 kg.The amnioticmembrane was artificially ruptured at 3 cm cervical dilation and a catheter was inserted into uterine cavity beyondthe head of the fetus and connected to a maternal-fetal monitor.The patients were randomly divided into 2 groupswith 20 patients in each group:Ⅰ control group received no analgesia and Ⅱ epidural group received continuousepidural analgesia(PCEA).An epidural catheter was placed at L_2-3.After a loading dose of 8-10 ml of the PCEAsolution(0.1% ropivacaine+1 ?g?ml~(-1) fentanyl)PCEA was started(bolus 3 ml,lockout interval 15 min andback ground infusion 6-8 ml?h~(-1)).The height of block was controlled below T_10.Blood samples were taken frommaternal vein at 3 cm cervical dilation(T_1),1h later(T_2)and at delivery(T_3)and from umbilical vein andamniotic fluid was aiso collected for determination of cortisol,PGE_2 and pitocin levels.VAS scores,intrauterinepressure,the frequency and duration of uterine contraction,the use of pitocin(%),incidence of cesareansection,the length of labor and neonatal Apgar scores were recorded.Results The maternal blood eortisolconcentration was significantly lower during PCEA(T_2,T_3)in group Ⅱ than in control group(P

Objective To investigate the effect of dexamethasone on the pulmonary gas exchange in patients undergoing cardiac valve replacement under cardiopulmonary bypass(CPB).Methods Forty ASAⅡorⅢpatients aged 29-47 yrs weighing 50-69 kg undergoing cardiac valve replacement under CPB were randomly divided into 2 groups(n=20 each):dexamethasone group received dexamethasone 0.5 mg?kg~(-1) after induction of anesthesia and control group received normal saline(NS).Blood samples were taken before operation(T_0) immediately before CPB(T_1)and immediately after discontinuation of CPB(T_2)for determination of plasma total and active matrix metallo-proteinase-9(MMP-9)concentration(by enzyme-linked immuno-absorbent and fluorometric enzyme-linked immuno-absorbent assay respectively)and MMP-9 gene expression(RT-PCR).Blood samples were taken from radial artery at T_1 and T_2 for blood gas analysis.A-aDO_2 was calculated.Results MMP-9 gene expression and plasma total and active MMP-9 concentrations were significantly increased at T_2 as compared with those at T_0 in both groups and were significantly lower in dexamethasone group than in control group(P＜0.05 or 0.01).The A-aDO_2 at T_2 was significantly smaller in dexamethasone group than in control group.Conclusion Dexamethasone can inhibit the increase in gene expression,protein synthesis and activation of MMP-9 and decrease in gas exchange across alveolar-capillary membrane caused by CPB and protect the lungs during open heart surgery performed under CPB.

Objective To investigate the mechanisms of the inhibitory effects of peripheral electrical stimu- lation(PES)on chronic central pain(CCP)after spinal cord injury(SCI).Methods Twenty-four male Sprague- Dawley rats with CCP following SCI were randomly divided into three groups:a group without stainless steel needles implanted (NSSN group,n=8),a group with a stainless steel needle implanted but no peripheral electrical stimula- tion applied(NPES group,n=8)and a PES group(PES group,n=8).The rats' CCP was evaluated through ob- serving their response to nociceptive stimulation by means of the paw withdrawal pressure threshold(PWPT)and the paw withdrawal latency(PWL).Spontaneous pain behaviors including autophagia and scratching were observed at the same time.PES was applied via stainless steel needles inserted into standard acupoints on the hind limps and the back.The expression of the NMDA receptor 1(NR-1)subunit in the spinal cord horn was measured using immuno- chemical methods.Results Compared with the NSSN and NPES groups,CCP in the PES group was alleviated, PWPT and PWL were dramatically increased(P＜0.01)and the expression of NR-1 was obviously decreased (P＜0.01).Conclusion Peripheral electrical stimulation may alleviate chronic central pain after spinal cord injury in rats.

Objective To study the protective role of AngiotensinⅡreceptor inhibitor in ventilator-induced lung injury of rats.Method Forty healthy male SD rats were equally divided into four group (A,B,C,D group,n=10).Group A served as control group,group B had low tidal volume (V_T=10 ml/kg) with breathing rate (P)=80/min;group C had high tidal volume (V_T=40 ml/kg) group with breathing rate 80/min;group D had high tidal volume (V_T=40 ml/kg) group with breathing rate 80/min,all rats in group D were pretreated with Losartan.The duration of ventilation in 'all groups was two hours.Rats were sacrificed after experiment finished. The lung lavage liquid and lung tissue were collected and preserved with well established methods.Lung pathological change was observed by microscope;lung cell apoptosis was assessed with TUNEL;the expression of ANGⅡwas assayed with RT-PCR.The measured variables also included total protein,WBC,W/D,MPO. Results In comparison with B group,all variables in group C were significantly increased (P

BACKGROUNDUrinary trypsin inhibitor inhibits the enhanced production of pro-inflammatory molecules. Hemeoxygenase-1 induction protects against ischemia/reperfusion injury, oxidative stress, inflammation, transplant rejection, apoptosis, and other conditions. However, it is unknown if a combined hemin and ulinastatin pretreatment could result in protective effects for septic shock. In this study, we investigated the role of hemin pretreatment combined with ulinastatin on septic shock in rats.

METHODSEighty healthy, male Sprague-Dawley rats were randomly divided into four groups: group S, group H, group U and group HU. Groups S and U received 1 ml normal saline intraperitoneally, while groups H and HU both received 1 ml (100 mg /kg) hemin. Twenty-four hours later, 0.5 ml (10 mg/kg) E. coli lipopolysaccharide was injected intravenously to replicate the experimental model of septic shock. After an initial 25% decrease in the mean arterial pressure, corresponding to time point 0, groups HU and U received 0.5 ml 10 000 U/kg ulinastatin intravenously, and the others received 0.5 ml normal saline.

RESULTSThe number of deaths in groups H and U was lower than that in the group S (P < 0.05), and was higher than that in group HU (all P < 0.05) respectively. The mean arterial pressure (MAP) in the group S was significantly greater than that in group H (P < 0.05), and was lower than that in group HU and group U (P < 0.05). The plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and blood urea nitrogen (BUN), the malondial-dehyde (MDA) of liver, kidney and lung, and the lung Evans blue (EB) contents in groups H and U, were greater than that in group HU (all P < 0.05), and were lower than that in group S (all P < 0.05). In contrast, the plasma levels of CO in groups H and HU were higher than that in groups S and U (all P < 0.05), and SOD of liver, kidney and lung in groups H and U were higher than that in group S, and were lower than that in group HU (all P < 0.05). The levels of TNF-alpha, IL-6, IL-8 and beta-glucuronidase (GCD) activity of plasma in groups U and HU were lower than those in groups H and S, all having a P < 0.05, while there were no significant differences between group H and group S, or between group HU and group U (all P > 0.05). The HO-1 mRNA and HO-1 protein levels from hepatic, renal, and pulmonary tissue in groups S and U were lower than those in groups H and HU (all P < 0.05), but there were no significant differences between groups S and U, or between groups H and HU (all P > 0.05). The HO-2 mRNA and HO-2 protein were not significantly different among the four groups (all P > 0.05).

CONCLUSIONSCombined pretreatment with hemin and ulinastatin in septic shock rats results in an improved response by the upregulation of HO-1 protein followed by increasing CO with resistance to increased oxidative stress, restraining the release of inflammatory mediators, and inhibiting beta-GCD activity.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Pressure ; drug effects ; Blood Urea Nitrogen ; Creatinine ; blood ; Cytokines ; blood ; Glycoproteins ; therapeutic use ; Heme Oxygenase (Decyclizing) ; analysis ; genetics ; Hemin ; therapeutic use ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; drug therapy ; physiopathology ; Superoxide Dismutase ; metabolism

Mechanical ventilation (MV) with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses,resulting in ventilator-induced lung injury (VILI).The mechanisms of the injurious effects of MV and the genetic susceptibility remain unclear.VILI-related genes such as cysteine-rich angiogenic inducer 61 (Cyr61)have been demonstrated to play a detrimental role in the aggressive ventilation strategies.In the present study,we investigated the involvement of Cyr61 in the VIM and the underlying mechanism.A549 cells were exposed to cyclic stretch of varying durations and then the mRNA and protein levels of Cyr61 were measured by real-time PCR and Western blotting,respectively.Additionally,after exposure ofA549 cells to cyclic stretch for 5 min to 1 h,the expression levels of nuclear factor kappaB (NF-κB) and IL-8 were detected by ELISA and Western blotting.Thereafter,Cyr61 expression was depressed in A549 cells with the siRNA pGenesill.1-Cyr61-3 before the cyclic stretch,and IL-8 secretion and the activation of NF-κB pathways were probed by ELISA and Western blotting,respectively.Moreover,a NF-κB inhibitor (PDTC) and an activator (TNF) were used before mechanical stretch.Realtime PCR and ELISA were performed to detect the mRNA and protein of IL-8,respectively.The results showed that the mechanical cyclic stretch led to increased Cyr61 expression at mRNA and protein levels in A549 cells.Additionally,cyclic stretch also mobilized NF-κB from the cytoplasm to the nucleus and increased IL-8 secretion in A549 cells.The inhibition of Cyr61 blocked the NF-κB activation and IL-8 secretion in response to cyclic stretch.Inhibition of NF-κB attenuated the mRNA and protein expression of IL-8 in A549 cells transfected with Cyr61 siRNA.It was suggested that Cyr61/NF-κB signaling pathway mediates the upregulation of IL-8 in response to cyclic stretch in A594 cells.These findings support the hypothesis that Cyr61 plays a critical role in acute lung inflammation triggered by mechanical strain.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Chemokine CCL2 ; analysis ; Immunohistochemistry ; Lipopolysaccharide Receptors ; analysis ; genetics ; Lipopolysaccharides ; toxicity ; Lung ; pathology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis ; Ventilators, Mechanical ; adverse effects

BACKGROUNDIsoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1, 4, 5-trisphosphate (IP(3)) receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species (ROS).

METHODSPrimary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration (MAC) of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca(2+)](c), and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP(3) receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.

RESULTSIsoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat cortical neurons, which was also associated with a high and fast elevation of peak [Ca(2+)](c). Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca(2+)](c) in primary rat cortical neurons.

CONCLUSIONThese results suggested that isoflurane induced elevation in [Ca(2+)](c), partially via elevated activity of IP(3) receptors, which rendered cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane, at an equivalent exposure to isoflurane, did not induce similar elevations of [Ca(2+)](c) or neurotoxicity in primary cortical neurons of rat.

Anesthetics, Inhalation ; toxicity ; Animals ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Inositol 1,4,5-Trisphosphate Receptors ; drug effects ; physiology ; Isoflurane ; toxicity ; Methyl Ethers ; toxicity ; Rats ; Reactive Oxygen Species ; metabolism