A study of anaesthesia-related cardiac arrest from a Chinese tertiary hospital.

BACKGROUND: The present survey evaluated the incidence of perioperative cardiac arrests in a Chinese tertiary general teaching hospital over ten years. METHODS: The incidence of cardiac arrest that occurred within 24 h of anaesthesia administration was retrospectively identified in the Third Affiliated Hospital of Sun Yat-Sen University between August 2007 and October 2017. Overall, 152,513 anaesthetics were included in the study period. Data collected included patient characteristics, American Society of Anaesthesiologists (ASA) physical status score, surgical specialty and anaesthesia technique. Cardiac arrests were assigned to one of three groups: "anaesthesia-related", "anaesthesia-contributing" or "anaesthesia-unrelated". RESULTS: In total, 104 cardiac arrests (6.8:10,000) and 34 deaths (2.2:10,000) were obtained. Among them, eleven cardiac arrests events were anaesthesia-related, resulting in an incidence of 0.7 per 10,000 anaesthetics. Sixteen cardiac arrests events were found to be anaesthesia-contributing, resulting in an incidence of 1.0 per 10,000 anaesthetics. Cardiovascular adverse events were the major events that contributed to anaesthesia-related cardiac arrest. Differences were found between events related and unrelated to anaesthesia with regard to ASA physical status and anaesthesia technique (P < 0.05). CONCLUSIONS: Anaesthesia-related cardiac arrest occurred in 11 of 104 cardiac arrests within 24 h of anaesthesia administration. Most cardiac arrests related to anaesthesia were due to cardiovascular events, including arrhythmia and hypotension after intravenous narcotic, as well as haemorrhage. ASA physical status of at least 3 and subarachnoid block appeared to be relevant risk factors for anaesthesia-related cardiac arrest.

Effect of dexmedetomidine for attenuation of propofol injection pain in electroconvulsive therapy: a randomized controlled study.

PURPOSE: Current analgesic strategies for propofol injection pain may cause adverse reactions during electroconvulsive therapy (ECT), such as shortening seizure duration. This study investigated whether dexmedetomidine could attenuate propofol injection pain in ECT. METHODS: Participants were randomly allocated to receive 0.2 µg/kg dexmedetomidine (Dex-0.2 group), 0.5 µg/kg dexmedetomidine (Dex-0.5 group) or saline (control group) prior to ECT. The composite pain scale and objective Surgical Pleth Index (SPI) were used to measure the intensity of injection pain, and the percentage of patients with pain score > 2 was the primary outcome. RESULTS: Of 137 patients recruited, 46 were assigned to each of the Dex-0.2 or Dex-0.5 groups, while 45 were in the control group. The percentage of pain score > 2 was reduced from 68.9% (31/45) in the control group to 34.8% (16/46) in the Dex-0.2 group (P < 0.001) and 15.2% (7/46) in the Dex-0.5 group (P < 0.001). The pain score and SPI at 5 s after propofol injection were greater in the control group than in the Dex-0.2 [pain scores 3 (2-4) vs. 1 (1-3), P < 0.001, SPI 76.6 ± 10.0 vs. 58.0 ± 11.0, P < 0.001] and Dex-0.5 groups [pain scores 3 (2-4) vs. 1 (0-1), P < 0.001, SPI 76.6 ± 10.0 vs. 51.2 ± 12.3, P < 0.001]. There were no significant differences in seizure duration between the three groups. No patients developed bradycardia and hypotension. CONCLUSIONS: Pretreatment with dexmedetomidine was able to reduce the propofol injection pain in ECT without interfering with the seizure duration and causing adverse effects such as bradycardia and hypotension. In addition, close monitoring of hemodynamic variables and preparation of a treatment plan and drugs for bradycardia are essential.

Dexmedetomidine Combined With Intravenous Anesthetics in Electroconvulsive Therapy: A Meta-analysis and Systematic Review.

OBJECTIVE: The aim of this study was to investigate how the combined use of dexmedetomidine with intravenous anesthetics influences seizure duration and circulatory dynamics in electroconvulsive therapy (ECT). METHODS: A literature search was performed to identify studies that evaluated the effect of dexmedetomidine on motor- or electroencephalogram (EEG)-based seizure durations and maximum mean arterial pressure (MAP) and heart rate (HR) after ECT. Moreover, recovery time and post-ECT agitation were evaluated. RESULTS: Six studies enrolling 166 patients in 706 ECT sessions were included. There was no significant difference in motor or EEG seizure duration between dexmedetomidine and nondexmedetomidine groups [motor: 6 studies; mean difference (MD), 1.62; 95% confidence interval (CI), -2.24 to 5.49; P = 0.41; EEG: 3 studies; MD, 2.34; 95% CI, -6.03 to 10.71; P = 0.58]. Both maximum MAP and HR after ECT were significantly reduced in the dexmedetomidine group (MAP: 6 studies; MD, -4.83; 95% CI, -8.43 to -1.22; P = 0.009; HR: 6 studies; MD, -6.68; 95% CI, -10.74 to -2.62; P = 0.001). Moreover, the addition of dexmedetomidine did not significantly prolong recovery time when the reduced-dose propofol was used (4 studies; MD, 63.27; 95% CI, -15.41 to 141.96; P = 0.12). CONCLUSIONS: The use of dexmedetomidine in ECT did not interfere with motor and EEG seizure durations but could reduce maximum MAP and HR after ECT. Besides, the addition of dexmedetomidine in ECT did not prolong recovery time when reduced-dose propofol was used. It might be worthwhile for patients to receive dexmedetomidine before the induction of anesthesia in ECT.

Ulinastatin prevents acute lung injury led by liver transplantation.

BACKGROUND: Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism. MATERIALS AND METHODS: Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed. RESULTS: According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1ß, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1ß, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1ß, IL-6, and MDA levels and SOD activity. CONCLUSIONS: UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.

In Vivo Evaluation of the Ameliorating Effects of Small-Volume Resuscitation with Four Different Fluids on Endotoxemia-Induced Kidney Injury.

Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.

Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.

Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P < 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

[Effects of cromolyn sodium on intestinal ischemia-reperfusion injury by inhibiting PAR-2 expression in rats].

OBJECTIVE: To explore the effects of cromolyn sodium (CS) on intestinal ischemia-reperfusion (IIR) and its relationship with mast cell activation and protease-activated receptor 2 (PAR-2) expression. METHODS: A total of 32 SD rats were randomly divided into 4 groups: sham-operated (S), intestinal ischemia reperfusion (IIR), CS (a mast cell stabilizer, CS, 25 mg/kg) and compound 48/80 (a mast cell degranulation, CP, 0.75 mg/kg) (n = 8 each). IIR was induced by clamping superior mesenteric artery for 75 min followed by reperfusion for 3 hours. The above agents were intravenously administrated at 5 min pre-reperfusion. Rats were then sacrificed and intestinal issues harvested for histological examinations. The tryptase expression and mast cell count were analyzed by immunohistochemistry. PAR-2 was analyzed by Western blot. RESULTS: The Chiu's score (0.75 ± 0.21), mast cell count (10 ± 3), tryptase expression (125 ± 15) and PAR-2 expression (109 ± 10) of group S were the least while those of group CP the most (all P < 0.05). The Chiu's score (2.14 ± 0.64), mast cell count (15 ± 4), tryptase expression (138 ± 17) and PAR-2 expression (124 ± 12) of group CS were less than those of groups IIR and CP (all P < 0.05). CONCLUSION: Cromolyn sodium may reduce IIR injury by stabilizing mast cell membrane and inhibiting the expressions of tryptase and PAR-2.

[Peri-operative characteristics of cerebral oxygen metabolism in patients with encephalopathy after orthotopic liver transplantation].

OBJECTIVE: To investigate the feature of cerebral oxygen metabolism during peri-operative stage of orthotopic liver transplantation (OLT), in order to identify the difference between the patients with or without complicating encephalopathy after OLT, and the relationship between the cerebral oxygen metabolism and encephalopathy after OLT. METHODS: Thirty patients undergoing OLT were studied. The patients were divided into two groups according to occurrence or not of encephalopathy after OLT: encephalopathy group and non-encephalopathy group. Blood samples were taken from radial artery and jugular vein simultaneously for blood gas analysis before operation, 25 minutes after onset of anhepatic phase, 30 minutes after graft reperfusion , 3 hours after graft reperfusion , and 24 hours after graft reperfusion. Cerebral arterial oxygen content (CaO(2)), oxygen content of jugular vein blood (CjvO(2)), cerebral arterial-venous oxygen content difference (Ca-jvO(2)), cerebral oxygen extraction ratio (CERO(2)) and cerebral blood flow/cerebral metabolic rate of oxygen ratio (CBF/CMRO(2)) were calculated, and the levels of blood glucose and lactic acid were recorded. RESULTS: There were 11 patients (36.7%) complicated by encephalopathy after OLT. The quantity of red blood cell infusion, blood loss and the dosage of noradrenalin in encephalopathy group were significantly larger compared with non-encephalopathy group. The overall tendency of change in cerebral oxygen metabolism index was about the same for both groups, while CaO(2) and Ca-jvO(2) at 25 minutes after onset of anhepatic phase, 30 minutes after graft reperfusion and 3 hours after graft reperfusion , and CERO(2) at 30 minutes after graft reperfusion and 3 hours after graft reperfusion were significantly decreased compared with those before operation [CaO(2) (ml/L) in encephalopathy group: 132.4 ± 23.5 , 125.9 ± 17.6, 133.4 ± 11.1 vs. 148.5 ± 28.8, in non-encephalopathy group: 135.7 ± 22.4, 130.5 ± 20.0, 139.9 ± 21.2 vs. 148.9 ± 28.2; Ca-jvO(2) (ml/L) in encephalopathy group: 42.9 ± 13.2, 31.4 ± 12.3 , 32.3 ± 6.5 vs. 52.9 ± 23.5, in non-encephalopathy group: 33.0 ± 14.1, 26.6 ± 9.1, 30.6 ± 10.3 vs. 50.2 ± 23.2; CERO(2) in encephalopathy group: (24.9 ± 9.7)%, (24.4 ± 5.5)% vs. (35.4 ± 11.5)%, in non-encephalopathy group: (20.6 ± 7.3)%, (21.9 ± 7.0)% vs. (33.4 ± 13.1)%, all P < 0.05], and they returned to the levels before operation at 24 hours after graft reperfusion. Jugular venous oxygen saturation (SjvO(2)) and CBF/CMRO(2) ratio were significantly increased at 30 minutes after graft reperfusion and 3 hours after graft reperfusion compared with the levels before operation [SjvO(2) in encephalopathy group: 0.838 ± 0.105, 0.835 ± 0.065 vs. 0.709 ± 0.125, in non-encephalopathy group: 0.854 ± 0.074, 0.824 ± 0.074 vs. 0.713 ± 0.138; CBF/CMRO(2) ratio in encephalopathy group: 37.8 ± 16.6, 31.9 ± 6.8 vs. 20.9 ± 6.7 , in non-encephalopathy group: 37.8 ± 14.1, 35.7 ± 13.7 vs. 24.3 ± 14.0, all P <0.05], and they returned to the levels before operation at 24 hours after graft reperfusion. The overall tendency of change in blood glucose and lactic acid was about the same in both groups, while the levels of blood glucose increased significantly from anhepatic phase to 24 hours after graft reperfusion compared with the levels before operation , and the levels of lactic acid increased significantly from anhepatic phase to 3 hours after graft reperfusion compared with the levels before operation and returned to the levels before operation at 24 hours after graft reperfusion. CONCLUSION: There are significant changes in the features of cerebral oxygen metabolism during OLT, but there is no difference between encephalopathy group and non-encephalopathy group. The occurrence of encephalopathy can be attributed to many factors, so the prevention and treatment should be comprehensive considered.

Effects of propofol intravenous injection bolus on the left ventricular function and the myocardial beta-adrenoceptor in rats.

Propofol bolus injection has been reported to influence cardiovascular functions. However, the detailed mechanism underlying this action has not been elucidated. This study was designed to investigate the effects of propofol i.v. bolus on the left ventricular function, the myocardial beta-adrenoceptor (beta-AR) binding-site density (Bmax) and Kd (apparent dissociation constant) in a 30-minute period. One hundred and four male Wistar rats were randomly divided into four groups: group C (control group), group I (intralipid group), group P1 (5 mg/kg propofol) and group P2 (10 mg/kg propofol). The results showed a significant downregulation of HR, LVSP, +dp/dtmax and -dp/dtmax in both groups P1 and P2 (especially after bolus injection in 7 min) than those of group C (P < 0.05), whereas no significant difference was found between the P1 and P2 groups (P > 0.05). Likely, Bmax was remarkably upregulated in both groups P1 and P2 (P < 0.05, vs. groups C and I), and there was no significant difference between these two groups (P > 0.05). Of note, the Kd value in group P2 (10 mg/kg propofol) was found dramatically increased in 30 min than that in the low-dose propofol-treated group (group P1) as well as in groups C and I (P < 0.05). In conclusion, these results indicate that intravenous injection of propofol bolus can inhibit the cardiac function partially via upregulation of Bmax and downregulation of the beta-AR affinity at higher-dose injection of propofol bolus.

[Protective effects of ulinastatin during orthotopic liver transplantation on kidney function with decreasing acute renal failure after liver transplantation in patients with severe hepatitis].

OBJECTIVE: To study whether using ulinastatin (UTI) during orthotopic liver transplantation (OLT) can decrease acute renal failure after liver transplantation in patients with Severe Hepatitis. METHOD: Thirty-one patients with Severe Hepatitis undergoing orthotopic liver transplantation (OLT) were studied. They were devided into two groups: determination of serumbeta(2) microglobulin (beta(2) MG), BUN and Cr before operation and 24 h after operation, at the same time, urine samples were taken for determination of urine beta(2) MG. Data of HR, ABPM, CVP, CO were recorded during operation. The Incidence of renal failure affiliated liver transplantation (RFALT) and prognosis of these patients were also recorded in the two groups after operation. RESULTS: (1) 4 cases in group U while 10 cases in group C developed RFALT at 24 h after operation (P < 0.05). In these patients who developed RFALT at 24 h after operation, 4 cases were all rehabilitation discharge in group U, while in group C, 2 cases died, 3 cases didn't cure but required discharge, only 5 cases were rehabilitation discharge. (2) Compared with baseline before operation, serum beta(2) MG, Urine beta(2) MG, BUN and Cr increased significantly at 24 h after operation both in two groups, (P < 0.05, P < 0.01). (3) Compared with group C, serum beta(2) MG, Urine beta(2) MG, BUN increased significantly at 24 h after operation in group U (P < 0.05, P < 0.01). CONCLUSION: Protective effects of ulinastatin during orthotopic liver transplantation on kidney function in patients with Severe Hepatitis can decrease acute renal failure after liver transplantation.

[The comparative proteomic analysis of serum cytokine expression in acute lung injury patients in peri-operative stage of liver transplantation].

OBJECTIVE: To investigate the characteristics of serum cytokine expression in acute lung injury (ALI) patients in peri-operative stage of liver transplantation with the aim of setting the basis for screening the early markers and treatment targets of ALI. METHODS: Four male patients with ALI occurring in peri-operative stage of liver transplantation for hepatitis B liver cirrhosis, with no lung, renal, or brain abnormality, without difference in clinical findings (urine volume, blood loss, ascites, amount of blood transfusion, operation time, anhepatic time, the use of vaso-active drugs, diuretics and condition of circulation) were included for study. Blood was taken after anesthesia, 3 hours and 24 hours after new liver. RayBio human antibody array was used to analyze the cytokine expression. RESULTS: Compared with healthy people, in the patients with ALI in peri-operative stage of liver transplantation, upregulation of some cytokines appeared as early as after anesthesia, including interleukins (IL-3, IL-6, IL-12 p40, IL-12 p70), monocyte chemoattractant protein-2 (MCP-2), macrophage-colony stimulating factor (M-CSF), monokine induced by interferon-gamma (MIG), macro-phage inflammatory protein-1 alpha (MIP-1 alpha), soluble tumor necrosis factor receptor I (sTNFR I), especially sTNFR II which showed even stronger expression, while normal T cells expression and secretory factor (RANTES) and platelet-derived growth factor-BB (PDGF-BB) showed downregulation in expression. Some more cytokines showed upregulation in expression at neohepatic 3 hours, especially IL-12 p70, sTNFR I, sTNFR II showed upregulation, while RANTES, PDGF-BB and IL-1 alpha showed downregulation in expression. The number of cytokines showing upregulation was significantly increased at neohepatic 24 hours. Compared with those at neohepatic 3 hours, eotaxin, IL-1 alpha, IL-1 beta, IL-4, IL-15, MCP-2 showed significantly higher upregulation at neohepatic 24 hours, and among them IL-3 and IL-6 especially IL-2 showed even more upregulation in expression. CONCLUSION: There are changes in expression of different kinds of cytokines in various extent before operation, at neohepatic 3 hours and neohepatic 24 hours. Some of them may be considered as important early markers and treatment targets. Further researches with large samples would be necessary to elucidate the clinical implication.

[Changes in plasma S-100 beta and neuron-specific enolase in peri-operative period of orthotopic liver transplantation and its relationship with encephalopathy after operation].

OBJECTIVE: To observe the changes in plasma S-100 beta and neuron-specific enolase (NSE) and to study their relationship with encephalopathy after orthotopic liver transplantation (OLT). METHODS: Thirty patients without neurological disease undergoing OLT were studied. Plasma S-100 beta and NSE were examined at three time points: after induction of anesthesia (T1), at the end of operation (T2) and 24 hours after reperfusion of the transplant (T3). The difference of plasma S-100 beta and NSE between encephalopathy group and non-encephalopathy group was analyzed. RESULTS: Eleven patients were complicated with encephalopathy after OLT. In 30 patients, S-100 beta at T2 [(3.715+/-1.523) microg/L] was higher than that at T1 [(1.478+/-0.809) microg/L, P<0.01]; S-100 beta at T3 [(1.765+/-0.894) microg/L] decreased to normal level (T1). NSE at T2 [(26.684+/-7.973) microg/L] was higher than that at T1 [(14.012+/-4.612) microg/L, P<0.01]. At T3, the level of plasma NSE [(18.105+/-7.345) microg/L] was decreased, but higher than that at T1. Plasma S-100 beta and NSE in encephalopathy group (11 cases) and non-encephalopathy group (19 cases) showed the same tendency of change as all of the patients. Plasma S-100 beta at T3 in encephalopathy group [(2.007+/-0.854)microg/L] was higher than that in non-encephalopathy group [(1.468+/-0.903) microg/L, P<0.05], and it was correlated with the presence of encephalopathy (r=0.385, P=0.039), but not at T1 and T2. Plasma NSE at three time points showed no relationship to the presence of encephalopathy. CONCLUSION: The increase in plasma S-100 beta and NSE during OLT indicates the occurrence of damage to the brain. But plasma S-100 beta and NSE cannot predict encephalopathy after OLT.

Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions.

Neuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein-protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C-C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.

Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats.

BACKGROUND: Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats. METHODS: 120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg.kg-1, CS 50 mg.kg-1, and CP 0.75 mg.kg-1 i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 of the small intestine were detected at the same time. RESULTS: Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-alpha in intestine increased significantly compared with group S (P < 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (P < 0.05), attenuated the down-regulation or up-regulation of the above index (P < 0.05). Treatment with CP decreased the survival rate on the 3rd day after reperfusion compared with group M(P < 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(P > 0.05). CONCLUSION: Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.

Prognostic values of serum cystatin C and beta2 microglobulin, urinary beta2 microglobulin and N-acetyl-beta-D-glucosaminidase in early acute renal failure after liver transplantation.

BACKGROUND: Acute renal failure (ARF) after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation (OLT), and their feasibilities to predict early ARF after OLT were also analyzed. METHODS: Sixty patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum beta2 MG (n = 60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals: before operation (T0), 60 minutes after reperfusion (T3) and at the end of operation (T4). According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups: ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. RESULTS: Ten of sixty cases showed ARF (16.7%). The Logistic regression analysis showed that the levels of serum and urinary beta2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation (P < 0.05), while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2 MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P < 0.01), while only SCr showed significant difference between these groups at the end of operation (P < 0.01). CONCLUSIONS: The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2 MG, urinary beta2 MG and NAG in patients with early acute renal failure after liver transplantation.

Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase.

BACKGROUND: Berberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN). METHODS: Male Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods. RESULTS: The results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05). CONCLUSION: These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.

[Early risk factors of acute lung injury following orthotopic liver transplantation].

OBJECTIVE: To analyze the early risk factors of acute lung injury (ALI) following orthotopic liver transplantation (OLT). METHODS: Ninety-one patients with end-stage liver disease, 79 males and 12 females, underwent OLT. The general condition, serum total bilirubin, albumin, creatinine, and prothrombin activity, Child-Turcotte-Pugh (CTP) score, and model for end-stage liver disease (MELD) score 48 h before operation were recorded. The operation time, cold ischemia time of donor's liver, time of anhepatic phase, ascitic fluid, blood loss, RBC infusion amount, crystal infusion, and total infusion during operation were recorded too. Follow-up was conducted for 14 days to observe the clinical manifestation, and time of ventilatory support, arterial blood gas analysis and radiological examination of chest were performed. Univariate analysis and logistic stepwise regression analysis were done to investigate the early risk factors of ALI. RESULT: 53 patients (58.2%) suffered from pulmonary complications following OLT, including ALI (27.5%) and adult respiratory distress syndrome (ARDS) (5.5%). Univariate analysis showed that preoperative senior age, severe hepatitis B, high serum total bilirubin, low prothrombin activity, and high CTP and MELD scores, and large amount of blood loss and RBC infusion during operation were all risk factors of ALI following OLT (all P < 0.05). Logistic stepwise regression analysis screened out serum total bilirubin as an independent predictor for ALI following OLT. CONCLUSION: A little more than a quarter of the patients undergoing OLT develop ALI after operation. High preoperative serum total bilirubin is an important early risk factor for ALI following OLT.

Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). The pathogenic mechanisms of DPN and the therapeutic interventions required may be distinct between type 1 (T1) and type 2 (T2) DM. However, the molecular mechanisms underlying the pathogenesis of DPN in both types of diabetes remain unclear. The aim of the current study was to identify the changes in genes and pathways associated with DPN in sciatic nerves of T1- and T2DM mice using bioinformatics analysis. The microarray profiles of sciatic nerves of T1DM (GSE11343) and T2DM (GSE27382) mouse models were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in each. DEGs in the two types of DM (with fold change ≥2 and P<0.05) were identified with BRB-ArrayTools. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and visualized using Cytoscape. Compared with control samples, 623 and 1,890 DEGs were identified in sciatic nerves of T1- and T2DM mice, respectively. Of these, 75 genes were coordinately dysregulated in the sciatic nerves of both models. Many DEGs unique to T1DM mice were localized to the nucleoplasm and were associated with regulation of transcription processes, while many unique to T2DM mice were localized at cell junctions and were associated with ion transport. In addition, certain DEGs may be associated with the different treatment strategies used for the two types of DM. This analysis provides insight into the functional gene sets and pathways operating in sciatic nerves in T1- and T2DM. The results should improve understanding of the molecular mechanisms underlying the pathophysiology of DPN, and provide information for the development of therapeutic strategies for DPN specific to each type of DM.

Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats.

AIM: To investigate the effects of Cromolyn Sodium (CS) pretreated prior to reperfusion on the activity of intestinal mucosal mast cells (IMMC) and mucous membrane of the small intestine in ischemia-reperfusion (IR) injury of rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (group S), model group (group M), high and low dosage of CS groups, (treated with CS 50 mg/kg or 25 mg/kg, group C1 and C2). Intestinal IR damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. CS was intravenouly administrated 15 min before reperfusion. Ultrastructure and counts of IMMC, intestinal structure, the expression of tryptase, levels of malondisldehyde (MDA), TNF-alpha, histamine and superoxide dismutase (SOD) activity of the small intestine were detected at the end of experiment. RESULTS: The degranulation of IMMC was seen in group M and was attenuated by CS treatment. Chiu's score of group M was higher than the other groups. CS could attenuate the up-regulation of the Chiu's score, the levels of MDA, TNF-alpha, and expression of tryptase and the down-regulation of SOD activity and histamine concentration. The Chiu's score and MDA content were negatively correlated, while SOD activity was positively correlated to the histamine concentration respectively in the IR groups. CONCLUSION: Pretreated of CS prior to reperfusion protects the small intestine mucous from ischemia-reperfusion damage, the mechanism is inhibited IMMC from degranulation.

[Changes in renal function in patients with severe hepatitis and liver cancer with cirrhosis during orthotopic liver transplantation].

OBJECTIVE: To observe the changes in renal function in patients with severe hepatitis and liver cancer with cirrhosis during orthotopic liver transplantation (OLT). METHODS: Thirty end-stage liver disease patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) undergoing OLT were studied. They were divided into two groups: severe hepatitis group (group H, n=15) and liver cancer group (group C, n=15), and all the patients received modified piggyback liver transplantation without veno-venous bypass. During the operation, blood samples were drawn for the determination of serum beta (2)-microglobulin (beta (2)-MG), and the determination was performed at 5 following time points: before operation, 20 minutes before anhepatic phase, 30 minutes in anhepatic, 60 minutes after reperfusion, and the end of operation. Urine samples were collected for determination of urine beta (2)-MG and N-acetyl-beta-D-glucosaminidase (NAG) at 3 time points: before operation, 60 minutes after reperfusion, and the end of operation. The values of SCr and BUN before operation, 24 hours after operation and 1 week after operation. The incidence of renal function failure after liver transplantation in the two groups were recorded respectively. RESULTS: (1)In 7 patients. 12 patients and 14 patients whose serum beta (2)-MG, urine beta (2) MG and urine NAG were higher than normal values, respectively, in group H before operation, and in 3 patients, 3 patients and 7 patients whose serum beta (2)-MG, urine beta (2)-MG and urine NAG, respectively, were higher than normal values in group C before operation. The incidence of abnormal of urine beta (2)-MG and NAG in group H were significantly higher than those in group C (P<0.01, P<0.05 respectively),while there were no significant differences for the abnormal rate of serum beta (2)-MG at every time point between the two groups during operation (all P>0.05). (2)Compared with baseline, serum beta (2)-MG almost had no change in both groups. There were no significant differences in the variation and the mean value of serum beta (2)-MG at every time point between the two groups (all P>0.05). Compared with the baseline,urine beta (2)-MG and urine NAG were increased at 60 minutes after reperfusion and also at the end of operation in both groups, but the differences were not significant (P>0.05). Compared with group C, urine NAG increased at every time point during the operation in group H (P<0.05 or P<0.01). (3)Incidence of renal failure related with liver transplantation (RFALT):46.7% developed RFALT in group H at 24 hours after operation, and there was none in group C(P<0.01). CONCLUSION: Compared with patients with liver cancer with cirrhosis,the damages to renal function in patients with severe hepatitis before operation are more serious, which are mainly due to renal tubular injury. These patients are susceptible to RFALT, and protection of renal function is necessary.