Dexmedetomidine suppresses the decrease in blood pressure during anesthetic induction and blunts the cardiovascular response to tracheal intubation

Study ObjectiveTo evaluate the effect of dexmedetomidine combined with fentanyl on hemodynamics.DesignProspective, double-blinded, randomized study.SettingOperating room of a university hospital.Patients30 ASA physical status II and III patients with mild-to-moderate cardiovascular disease.InterventionsPatients were assigned to one of three groups: Group D-F2 [dexmedetomidine, effect-site concentration (ESC) of fentanyl = two ng/mL]; Group F2 (placebo, ESC of fentanyl = two ng/mL), or Group F4 (placebo, ESC of fentanyl = 4 ng/mL).MeasurementsDexmedetomidine (an initial dose of 1.0 μg/kg for 10 min, followed by a continuous infusion of 0.7 μg·kg^–1·hr^–1) or placebo saline was administered 15 minutes before anesthetic induction. Anesthesia was induced with propofol and fentanyl using a target-controlled infusion system. Hemodynamic parameters: systolic (SBP) and diastolic blood pressures (DBP), and heart rate (HR) during anesthetic induction were measured and the percent changes were calculated for both induction and intubation.Main ResultsAfter inducing anesthesia, SBP was significantly higher in Group D-F2 (127 ± 24 mmHg) than Group F2 (90 ± 20 mmHg) or Group F4 (77 ± 21 mmHg). The SBP in Groups F2 and F4 reached 160 ± 31 mmHg and 123 ± 36 mmHg, respectively, after intubation, but no significant change in SBP was noted in Group D-F2. The percent increase in SBP due to tracheal intubation in Group D-F2 was 3% ± 4% and was significantly lower than that of Group F2 (70% ± 34%) or Group F4 (45% ± 36%).ConclusionDexmedetomidine combined with fentanyl during anesthetic induction suppresses the decrease in blood pressure due to anesthetic induction and also blunts the cardiovascular response to tracheal intubation.     

The Effect of Surgically Induced Weight Reduction on the Serum Levels of the Cytokines: Interleukin-3 and Tumor Necrosis Factor

Background: Morbid obesity and malnutrition have both been demonstrated to have deleterious effects on the immune function. Cytokines are immunomodulatory peptides that have profound effects on immune function. To the authors' knowledge, the effect of surgically induced weight reduction on the cytokine levels has yet not been studied. In the present study, the authors determined the effect of surgically induced weight reduction on the levels of the cytokines interleukin-3 (IL-3) and tumor necrosis factor-α (TNF-α). Methods: 14 patients undergoing silicone ring vertical gastroplasty were included in the study (mean BMI 48.85 kg/m²; range 38.1-52.0 kg/m²). Determination of the IL-3 and TNF-α levels was performed preoperatively and 14 days and 6 months postoperatively, when all patients had lost 25% to 30% of their preoperative weight. Results: The IL-3 values before the procedure, and 14 days and 6 months after, were as follows: 9.69 ± 1.82, 9.36 ± 1.28, and 8.42 ± 1.26 pg/mL, respectively (P < 0.05 preoperative versus 6 months postoperative level). The preoperative TNF-α levels showed a wide distribution. For this reason, the patients were divided into two groups: Group A with preoperative values >10 pg/mL and Group B with values <10 pg/mL. In Group A, a significant decrease from the preoperative level of 24.46 ± 6.83 to 7.59 ± 4.56, and 6.69 ± 5.46 pg/mL was measured at 14 days and 6 months postoperatively, respectively (P < 0.05). In Group B, the TNF- α levels were not significantly changed and were 5.45 ± 2.26, 7.59 ± 4.56, and 8.82 ± 6.27 pg/mL, respectively. Conclusion: The present study demonstrates a significant decrease in the levels of the cytokines, IL-3 and TNF-α. These changes can be responsible for alteration of the immune function after surgically induced weight reduction.     

Bone-Resorbing Cytokines from Peripheral Blood Mononuclear Cells after Hormone Replacement Therapy: A Longitudinal Study

Conflicting results have been reported in several cross-sectional studies measuring cytokine production from adherent monocytes in pre- and postmenopausal women. Furthermore, the target cells for the action of estrogen are still debated. We therefore assessed in a longitudinal manner the cytokine production from different fractions of peripheral blood mononuclear cells (PBMC) cultured for 48 h. PBMC were obtained from 30 postmenopausal women before and after 6 months of hormone replacement therapy (HRT). Women were randomly allocated to two groups: an adherent PBMC group (n= 20) and a total PBMC group (n= 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353 ± 24 vs 114 ± 13 μg/mmol creatinine and 325 ± 35 vs 164 ± 31 μg/mmol creatinine respectively, p<0.01). Culture supernatants were assayed for interleukin 1β (IL-1β), interleukin 6 (IL-6), soluble IL-6 receptor (IL-6rs) and tumor necrosis factor alpha (TNF-α). In the adherent PBMC group, HRT induced a nonsignificant trend toward decreased levels of IL-1β (35 ± 10 vs 13 ± 5 pg/ml), TNF-α (333 ± 58 vs 222 ± 30 pg/ml) and IL-6 (115 ± 70 vs 17 ± 10 pg/ml). In contrast, in the total PBMC group, HRT induced a consistent and dramatic decrease in levels of IL-1β (104 ± 22 vs 25 ± 8 pg/ml), IL-6 (5950 ± 1041 vs 1011 ± 361 pg/ml), IL-6rs (148 ± 33 vs 35 ± 12 pg/ml) (p<0.01) and TNF-α (1468 ± 315 vs 585 ± 207 pg/ml, p= 0.05). We then evaluated whether HRT had the same effect in vitro. Adherent or total PBMC of 8 postmenopausal women were cultured with or without 10⁻⁸M 17β-estradiol or tibolone for 48 h. Production of IL-1β, TNF-α, IL-6 and IL-6rs was not affected by the presence of 17β-estradiol or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the response to HRT. HRT may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro effect. Received: 11 July 2000 / Accepted: 15 January 2001     

Modified extraperitoneal endoscopic separation of parts for abdominal compartment syndrome

Background Standard therapy for abdominal compartment syndrome (ACS) is laparotomy and temporary abdominal wall closure with significant morbidity. The component separation technique allows for difficult abdominal closure. We studied a modified extraperitoneal endoscopic separation of parts technique on an animal model of ACS. Methods Twelve anesthetized pigs were instrumented for measurement of central venous pressure, arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, and intraabdominal pressure (IAP). ACS to 25 mmHg was created by infusing saline into an intraabdominally placed bag. Animals were divided in two equal groups. Pigs in group A underwent minimally invasive resection of the nerves supplying the rectus muscles bilaterally. Pigs in group B underwent minimally invasive modified component separation technique bilaterally. Change in IAP and other physiological parameters were recorded. Results (Group A) IAP increased significantly from 7.3 mmHg ± 3.8 to 25.2 mmHg ± 1.5 with infusion of saline. Following nerve transection on the right side there was a nonsignificant decrease in IAP from 25.2 mmHg ± 1.5 to 22.3 mmHg ± 1.4 and following nerve transection on the left side there was a further decrease in IAP to 20.3 mmHg ± 1.9. (Group B) IAP increased significantly from 3.8 mmHg ± 0.4 to 24.7 mmHg ± 0.5 with infusion of saline. Following separation of parts on the right side there was a significant decrease in IAP from 24.7 mmHg ± 0.5 to 15.0 mmHg ± 1.7 and there was a further decrease in IAP to 11.3 mmHg ± 1.4 following separation of parts on the left side. The only significant change in the physiological parameters measured was observed in CVP in both groups. Conclusion We present a porcine model of extraperitoneal endoscopic release of abdominal wall components as a treatment option for ACS. Podium presentation at the 2004 meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Denver, CO, USA, 31 March–3 April 2004     

Optimal target concentration of remifentanil during cataract surgery with monitored anesthesia care

Study objectiveTo determine the effect-site target concentration (C_et) of remifentanil that provides optimal conditions for patients and operators during cataract surgery during monitored anesthesia care using a target controlled infusion (TCI) of propofol and remifentanil.DesignProspective, randomized, double-blinded study.SettingOperating room and postoperative recovery area of a university-affiliated hospital.Patients66 adult, ASA physical status I, II, and III patients undergoing cataract surgeryInterventionsGroup I received C_et of remifentanil 0.5 ng/mL; Group 2 received C_et of remifentanil one ng/mL; and Group 3 received C_et of remifentanil 1.5 ng/mL. After giving TCI propofol (C_et; one μg/mL) - remifentanil, an ophthalmologist administered topical anesthesia.Measurements and main resultsIntraoperative hemodynamics, pain scores, sedation scores, patient satisfaction scores, and operators’ satisfaction scores regarding surgical conditions were recorded. No statistical differences in heart rate or mean blood pressure were detected among the three groups during surgery. Pain scores (Group 1: 31.9 ± 17.9 vs. Group 2: 11.8 ± 7.7 and Group 3: 11.8 ± 7.7; P < 0.05) were higher and patient satisfaction scores (Group 1: 4.7 ± 0.8 vs. Group 2: 5.4 ± 0.4 and Group 3: 5.5 ± 0.4; P < 0.05) were lower in Group 1 than Groups 2 and 3. On the other hand, surgeon satisfaction was lowest in Group 3 (Group 3: 2.9 ± 1.3 vs. Group 1: 4.7 ± 0.4 and Group 2: 4.6 ± 0.7; P < 0.05) due to ocular movement.ConclusionC_et values of remifentanil and propofol of one ng/mL and one μg/mL, respectively, appear to provide optimal conditions for patients and operators during cataract surgery using monitored anesthesia care with TCI.     

Does epidural versus combined spinal-epidural analgesia prolong labor and increase the risk of instrumental and cesarean delivery in nulliparous women?

Study ObjectiveTo compare duration of labor, mode of delivery, and local anesthetic consumed in women who received labor analgesia with epidural or combined spinal-epidural technique.DesignRetrospective, observational study.SettingDelivery room of a university hospital.Patients788 nulliparous women in labor at term with cervical dilation between three and 5 cm.InterventionsIn Group E (epidural alone), parturients received an epidural solution of 8 mL (levobupivacaine 0.125% with fentanyl 5 μg/mL). In Group CSE (combined spinal-epidural), parturients received a spinal injection of levobupivacaine two mg with fentanyl 15 μg (total volume two mL). Then an epidural catheter was placed in all patients and connected to a patient-controlled analgesia pump (basal infusion rate of 8 mL/hr of 0.1% levobupivacaine and fentanyl two μg/mL, patient-controlled bolus dose of three mL, and lockout time of 30 min).MeasurementsLabor duration, mode of delivery (spontaneous vaginal vs. instrumental delivery vs. cesarean section), and local anesthetic consumed, were recorded.Main ResultsLabor analgesia was performed with an epidural technique in 322 patients (40.9%), and a combined spinal-epidural technique in 466 patients (59.1%), of whom 39 Group E women (12.1%) and 46 Group CSE women (9.9%) required cesarean section (P=ns). No differences in the mode of delivery were observed between the groups. Time from analgesia to delivery (Group E: 217 ± 111 min vs. Group CSE: 213 ± 115 min; P=ns), and epidural local anesthetic consumed (Group E: 35 ± 20 mL vs. Group CSE: 33 ± 20 mL; P=ns), were similar in both groups.ConclusionsNo significant differences were observed between epidural and combined spinal-epidural given for labor analgesia in nulliparous women in duration of labor, mode of delivery, or local anesthetic consumed.     

The effect of HTK solution modification by addition of prolactin on biochemical indices reflecting ischaemic damage to porcine kidney

IntroductionThe aim of our study was to evaluate the impact of perfusion with HTK solution, modified by the addition of prolactin (PRI), on selected biochemical parameters of porcine renal damage within 24 and 48 hours after the onset of cold ischemia time.MethodsEach study group consisted of 10 adult pigs. During harvesting the kidneys were rinsed with Ringer's solution (group 1), HTK (group 2), and HTK+PRL in a dose of 0.2 mg/dL, 0.02 mg/dL, and 0.01 mg/dL in groups 3, 4 and 5, respectively. The levels of lactate dehydrogenase, asparagine (AST) and alanine aminotransferases, lactates, total protein, potassium and calcium were determined in the perfusate. After 24 and 48 hours the rinsing procedure and the abovementioned tests were repeated.ResultsAfter 24 hours of storage, in 4 groups, significantly lower levels of LDH (U/L) were recorded compared with HTK solution alone, namely 235 ± 93 versus 271 ± 125 (perfusion minute, 0), and 55 ± 21 versus 125 ± 94 (30th minute). Similar behavior pattern was presented by AST (U/L) and potassium (mmol/L), and the results were 31 ± 8 versus 35 ± 12 and 16 ± 10 versus 29 ± 14, and 12 ± 3 versus 16 ± 3 and 10 ± 1 versus 13 ± 1, respectively. The changes described above were not observed in the 48th hour of reperfusion.ConclusionOur study results indicate the possibility of cytoprotective action of PRL after adding it to the fluid perfusing kidneys during cold ischemia. This effect, observed after 24 hours of storage, was to a considerable extent dose dependent. In our experiment the effect was pronounced only at 0.02 mg/dL supply of PRL.     

乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义

目的探讨乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义。方法前瞻性纳入内蒙古医科大学附属医院2014年1月至2016年1月收治的乙型肝炎(HBV)性肝癌患者40例作为研究组,同期收集非肝炎性肝癌患者40例作为对照组。观察两组患者肿瘤微环境中CD4~+T细胞、CD8~+T细胞、Treg细胞水平,以及外周血中IL-2、IL-10、TGF-β水平。同时观察HBV DNA病毒载量与免疫指标的相关性。结果与对照组比较,研究组患者CD4+T细胞水平显著升高[(21.08±3.12)%vs(19.72±2.89)%,P=0.047],CD8+T细胞水平显著降低[(28.83±2.52)%vs(30.07±2.41)%,P=0.027],Treg细胞水平显著升高[(8.12±1.47)%vs(6.62±1.42)%,P0.001];IL-2水平显著降低[(15.48±4.30)pg/m L vs(27.28±5.95)pg/m L,P0.001),IL-10水平显著升高[(36.39±7.69)pg/m L vs(29.82±6.17)pg/m L,P0.001),TGF-β水平显著升高[(31.95±3.72)pg/m L vs(23.49±3.83)pg/m L,P0.001)。Pearson线性相关性分析显示,HBV DNA病毒载量与CD8+T细胞及IL-2水平负相关,与CD4+T细胞、Treg和TGF-β水平正相关(P0.05)。结论乙型肝炎性肝癌患者肿瘤组织微环境中淋巴细胞失衡,且与HBV DNA病毒载量有关。     

Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens

BACKGROUND AND OBJECTIVE: An alteration in production of both interleukin-10 (IL-10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL-10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL-10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL-10 circulating concentrations. METHODS: Thirty-two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme-linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively. RESULTS: In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51 mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38 +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/- 1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1 and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1) at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL-10 and NO. CONCLUSIONS: During the postoperative period, IL-10 overproduction does not correlate with the decrease in systemic NO concentration.     

Effect of polyflux membranes on the improvement of hemodialysis-associated eosinophilia: a case series

Hemodialysis-associated eosinophilia (HAE) is believed to be associated with allergic reactions to dialyzer materials. This study aimed to investigate the use of Polyflux membranes to improve HAE. Thirty-one patients suffering from HAE were included. Patients were dialyzed with polysulfone membranes when they developed HAE. After that, patients were dialyzed with Polyflux membranes three times every week, 4?h every time without changing the dialysis parameters and medication. Levels of peripheral eosinophils, hsCRP, IgE, C3a, IL-5 and peripheral CD4+ lymphocytes and CD8+ lymphocytes were assessed before Polyflux treatment, and at 4th, 8th and 12th weeks of treatment. Any symptoms including chest tightness and skin itching were observed during the study period. After 12 weeks of Polyflux membrane dialysis and compared with polysulfone membrane dialysis, levels of peripheral eosinophils were significantly decreased (1.26?±?0.61 vs. 0.71?±?0.29?×?10⁹/L, p?<?0.001); serum IL-5 levels were significantly decreased (24.43?±?10.21 vs. 9.11?±?4.21?pg/mL, p?<?0.001); and chest tightness and skin itching were significantly improved (45.2% vs. 19.4%, p?=?0.028). After 12 weeks, there was no significant change in serum levels of hsCRP (2.00?±?0.94 vs. 1.81?±?0.79?mg/L, p?=?0.352), IgE (104.61?±?98.79 vs. 114.95?±?101.07?IU/mL, p?=?0.422) and C3a (121.61?±?34.04 vs. 120.29?±?32.81?µg/L, p?=?0.316), and in peripheral levels of CD4+ (589?±?181 vs. 569?±?171?cells/mm³, p?=?0.672) and CD8+ (443?±?123 vs. 414?±?140 cells/mm³, p?=?0.395) cells. Eosinophil count was correlated with serum IL-5 levels (r?=?0.873, p?<?0.001). Changing to a Polyflux membrane may alleviate HAE and reduce serum IL-5 levels. Therefore, this could be a strategy to manage HAE in the clinical practice.     

CO_2气腹对大鼠重症急性胰腺炎胰腺病理变化及白介素1、2、6、10表达的影响

目的:探讨腹腔镜手术时CO2气腹对SD大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)胰腺局部病变及血淀粉酶、炎症细胞因子白细胞介素1、2、6、10的影响。方法:随机将雄性SD大鼠50只分为3组:Ⅰ组20只(CO2组),胰胆管逆行注射5%牛磺胆酸钠,制备SAP动物模型,用气腹机向大鼠腹腔内注入CO2,压力12mm Hg,维持30min;Ⅱ组20只建立SAP模型后关腹,不充入CO2;Ⅲ组10只(对照组)开腹翻动胰腺后关腹。各组均于术后2.5h处死动物,对胰腺组织行病理学检查,并测定血淀粉酶、IL-1、IL-2、IL-6及IL-10的变化。结果:Ⅰ、Ⅱ、Ⅲ组的病理组织学评分分别为(1.900±0.370)、(1.750±0.259)及(0.000±0.000);淀粉酶(U/L)为(6 769±2 216)、(5 241±2 048)及(1 610±414);IL-1(pg/ml)为(0.241±0.052)、(0.320±0.067)及(0.143±0.057);IL-2(pg/ml)为(4.480±1.582)、(5.288±0.973)及(4.762±0.812);IL-6(pg/ml)为(176.39±41.75)、(206.10±37.29)及(115.14±24.96);IL-10(pg/ml)为(171.10±28.73)、(182.26±28.09)及(97.79±20.65)。与Ⅱ组相比,Ⅰ组的IL-1及IL-6表达明显降低(P<0.05),血清淀粉酶、IL-2、IL-10及胰腺病理组织学评分差异无统计学意义(P>0.05)。结论:CO2气腹对SD大鼠SAP胰腺病理变化及白介素1、2、6、10表达改变无不利影响。     

Effect of the intraoperative wake-up test in sevoflurane-sufentanil combined anesthesia during adolescent idiopathic scoliosis surgery: a randomized study

Study ObjectiveTo investigate the effect of the intraoperative wake-up test on sevoflurane-sufentanil anesthesia for adolescent idiopathic scoliosis (AIS) surgery.DesignRandomized, double-blind, parallel trial.SettingOperating room.Patients30 ASA physical status 1 patients, aged 13 to 20 years, scheduled for AIS surgery.InterventionsPatients were randomized to two groups: Group W patients received sevoflurane-sufentanil combined anesthesia and underwent the intraoperative wake-up test; Group NW received sevoflurane-sufentanil combined anesthesia without the wake-up test. Anesthesia was induced with an intravenous (IV) injection of midazolam, propofol, and sufentanil and maintained with sevoflurane inhalation, a target-controlled infusion (TCI) of sufentanil, and IV infusion of cisatracurium besylate.MeasurementsThe primary outcome was postoperative delirium. Secondary outcomes were duration of surgery, duration of anesthesia, intraoperative blood loss and transfusion, exposure of drugs administered, time to eye opening, extubation, and consciousness.Main ResultsPostoperative delirium occurred in one patient from each group (P > 0.05). There were no significant differences between the two groups in duration of surgery (322 ± 65 min vs 336 ± 72 min), duration of anesthesia (356 ± 76 min vs 368 ± 81 min), intraoperative blood loss (1847 ± 423 mL vs 1901 ± 451 mL) and transfusion (1663 ± 398 mL vs 1649 ± 382 mL), average exposure of drugs (72 ± 13 mg vs 75 ± 15 mg for propofol, 116 ± 28 μg vs 109 ± 25 μg for sufentanil, and 22 ± 5 vs 23 ± 4 mg for cisatracurium), time to eye opening (4.7 ± 1.5 min vs 4.8 ± 1.4 min), extubation (7.5 ± 2.0 min vs 7.3 ± 2.2 min), and consciousness (8.9 ± 1.8 min vs 9.1 ± 2.1 min) (all P > 0.05).ConclusionsSevoflurane-sufentanil combined anesthesia provides hemodynamic stability and rapid recovery from AIS surgery. There is no correlation between the intraoperative wake-up test and postoperative delirium after sevoflurane-sufentanil combined anesthesia.     

Effect of a Miniaturized Cardiopulmonary Bypass System on the Inflammatory Response and Cardiac Function in Neonatal Piglets

The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1‐week‐old piglets were placed on a mild hypothermic CPB (32°C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin‐6 (IL‐6) and thrombin‐antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL‐6 and TAT immediately after CPB (4370 ± 2346 vs. 9058 ± 2307 pg/mL, P < 0.01 and 9.9 ± 7.7 vs. 25.1 ± 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 ± 0.03 vs. 0.11 ± 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 ± 2860 vs. 28 620 ± 15 552 dynes/cm⁵/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates.     

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.     

Gastric submucosal alleviated pro-inflammation cytokines mediated initial dysfunction of islets allografts

BackgroundThe liver and renal capsule are the most common site for experimental pancreatic islet transplantation, but it is not optimal. Gastric submucosa space may be an ideal site for islet transplantation; however, whether pro-inflammation factors mediated islet dysfunction could be avoided or alleviated is still unclear.MethodsIslets of Sprague Dawley (SD) rat were transplanted into the streptozotocin-induced diabetic SD rats. Transplantation sites included gastric submucosa (GS), intraportal vein (PV) and kidney capsule (KC), and the efficiency of glycemic control and site-specific differences of islet grafts were compared.ResultsWith limited number of islets (800 IEQ) transplanted, improvement of recipient glycometabolism was superior in the GS group. When transplanted with 1200 IEQ islets, the survival of islet grafts were significantly prolonged in the GS group (25.87 ± 4.08 days, compared to 15.97 ± 0.83 days and 17.33 ± 1.41 days in PV and KC groups, respectively, P < .05). Compared with the PV group, the levels of IL-1β and TNF-α were significantly depressed in GS group after 12 h transplantation (15.5 ± 0.70 pg/mL and 13.28 ± 2.80 pg/mL vs. 262.26 ± 53.37 pg/mL and 138.51 ± 39.58 pg/mL, P < .05).ConclusionsGastric submucosal would be a potential ideal site for islet transplantation in rat. Gastric submucosal might alleviate the early islet dysfunction triggered by the IL-1β and TNF-α, and which requires a low number of transplanted islets and have a good glycemic control in return.     

Intraabdominal hypertension/abdominal compartment syndrome after pelvic fractures: How they occur and what can be done?

BackgroundLimited data exist regarding intraabdominal hypertension/abdominal compartment syndrome (IAH/ACS) after pelvic fractures. We aimed to explore risk factors for IAH/ACS in pelvic fracture patients, assess the physiological effects of decompressive laparotomy (DL) on IAH/ACS, and generate an algorithm to manage IAH/ACS after pelvic fracture.Materials and methodsPelvic fracture patients were included based on the presence of IAH/ACS. Intraabdominal pressure (IAP) was measured through a Foley catheter. DL was performed in patients with refractory IAH or ACS. Multivariable linear regression was applied to assess associations between IAP levels (≥12 mmHg) and age, sex, injury severity score (ISS), pelvic fracture, volume of resuscitation fluids over 24 h and hemoglobin values. The Wilcoxon signed-rank test for paired samples was used to compare variables before and after DL.ResultsAmong 455 pelvic fracture patients, 44 (9.7%) and 5 (1.1%) were diagnosed with IAH and ACS, respectively. The volume of resuscitation fluids over 24 h exhibited a significant positive correlation with IAP levels (≥12 mmHg) (p = 0.002). The main findings during DL were edematous bowel (11/20) and retroperitoneal hematoma (7/20). DL caused a significant decrease in the mean IAP from 24.4 ± 8.5 mmHg to 13.4 ± 4.0 mmHg (p < 0.0001). Physiological parameters (APP, PaO2/FIO2 ratio, PIP, arterial lactate and UOP) were significantly improved after DL. The mortality rate was 15% in patients who underwent DL and 40% in ACS patients.ConclusionsIAH/ACS is common in pelvic fracture patients. The most effective method to decrease IAP in pelvic fracture patients is DL. Prophylactic DL is important for decreasing mortality as it prevents IAH from progressing to ACS. Massive fluid resuscitation is a significant risk factor for IAH/ACS. A pathway incorporating prophylactic/therapeutic DL and optimized fluid resuscitation to prevent and manage IAH/ACS after pelvic fractures may reduce morbidity and mortality.     

Chronic Changes of End-Systolic Pressure-Volume Relationship After Regional Myocardial Infarction

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO₂) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 ± 1.24 mmHg/mL, 1 hour 2.71 ± 1.06, 3 months 3.46 ± 1.51, 6 months 2.45 ± 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.128±, r = 0.454, p < 0.05), V₀, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 ± 22.5 mL; 1 hour -0.9 ± 11.6; 3 months 5.4 ± 10.9, 6 months 9.2 ± 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO₂ were unchanged over time after infarction (PVA: baseline 2097 ± 1526 mmHg/mL per 100 g^-1; 1 hour 1771 ± 699; 3 months 2483 ± 1086; 6 months 1,608 ±1,010, NS), (LVO₂: baseline 40.6 ± 13.1 ± 10–³ mL/100 g^-1 per beat^-1; 1 hour 42.9 ± 9.7; 3 months 35.0 ± 8.6; 6 months 31.2 ± 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V₀ after the increase in the acute phase. PVA and LVO₂ were not affected by this regional infarction either acutely or over 6 months.     

Moderate intermittent negative pressure increases invasiveness of MDA-MB-231 triple negative breast cancer cells

BackgroundTo investigate the effect moderate intermittent negative pressure breast reconstructive model exerts on human triple negative breast cancer cell (TNBC) invasion and explore the related mechanism.MethodsThe human TNBC cell line MDA-MB-231 was used. Cells in external volume expansion (EVE) group were exposed to an intermittent −25 mmHg for 12 h; the pressure for non-EVE group was constantly 0 mmHg. In vivo, MDA-MB-231 cell suspensions were injected subcutaneously into dorsal skin of nude mice (n = 27 mice/group). Tumors on mice in EVE group received −25 mmHg suction 3 h/day; while mice in non-EVE group were under normal pressure. Cell invasion assay, ELISA, RT-PCR, western blot analysis and immunohistochemistry were used to evaluate the inflammation, epithelial-mesenchymal transition (EMT) and angiogenesis between the two groups in both vitro and vivo experiments.ResultsMDA-MB-231 cells in the EVE group were more invasive and had higher expressions of IL-8 (30.02 ± 10.44 pg/ml vs. 18.82 ± 9.26 pg/ml, P < 0.05) and TNF-α (20.59 ± 4.72 pg/ml vs. 14.10 ± 3.36 pg/ml, P < 0.05) than the non-EVE group. Grafted MDA-MB-231 tumors in EVE group showed a more obvious epithelial-mesenchymal transition at 2 week and better angiogenesis at 2 and 4 week, respectively.ConclusionModerate intermittent negative pressure induces MDA-MB-231 cells to be more invasive. Future studies should figure out other effects this intervention may bring. Clinical studies should also be conducted to further evaluate its safety and optimize the clinical model.     

Attenuation of skeletal muscle ischemia/reperfusion injury by inhibition of tumor necrosis factor

Purpose: Tumor necrosis factor α (TNF-α) has been shown to play a role in pulmonary injury after lower-extremity ischemia/reperfusion (I/R). However, its role in direct skeletal muscle injury is poorly understood. The hypothesis that endogenous TNF production contributes to skeletal muscle injury after hindlimb I/R in rats was tested. Methods: Juvenile male Sprague-Dawley rats underwent 4 hours of bilateral hindlimb ischemia and 4 hours of reperfusion (IR) or sham operation (SHAM). A subset was treated with a soluble TNF receptor I construct (STNFRI, 10 mg/kg) 1 hour before ischemia (PRE) or at reperfusion (POST). Direct skeletal muscle injury (SMII) and muscle endothelial capillary permeability (MPI) were quantified by means of Tc⁹⁹ pyrophosphate and I¹²⁵ albumin uptake. Pulmonary neutrophil infiltration and hepatocellular injury were assessed by means of myeloperoxidase content (MPO) and aspartate aminotransferase (AST) concentrations, respectively. Serum TNF bioactivity was measured with the WEHI bioassay. Results: Hindlimb I/R (IR vs SHAM) resulted in a significant (P < .05) increase in the SMII (0.52 ± 0.06 vs 0.07 ± 0.01) and MPI (0.35 ± .04 vs 0.06 ± 0.01). Pretreatment with STNFRI (PRE vs IR) significantly ameliorated both SMII (0.30 ± 0.05 vs 0.52 ± 0.06) and MPI (0.23 ± 0.02 vs 0.35 ± 0.04), whereas treatment at reperfusion (POST vs IR) had no effect. Hindlimb I/R (IR vs SHAM) resulted in both significant pulmonary neutrophil infiltration (MPO 16.4 ± 1.06 U/g vs 11.3 ± 1.4 U/g) and hepatocellular injury (AST 286 ± 45 U/mL vs 108 ± 30 U/mL), but neither was inhibited by pretreatment with STNFRI before ischemia. Detectable levels of TNF were measured during ischemia in a significantly higher percentage of the IR group compared with SHAM (9 of 12 vs 3 of 12), and the maximal TNF values were also significantly greater (51.1 ± 12.6 pg/mL vs 5.5 ± 2.9 pg/mL). No TNF was detected in any treatment group during reperfusion nor after administration of the STNFRI. Conclusion: Acute hindlimb IR initiates a systemic TNF response during the ischemic period that is partly responsible for the associated skeletal muscle injury. (J Vasc Surg 1999;29:370-6.)     

Impact of Continuous Hemofiltration on Cytokines and Cytokine Inhibitors in Oliguric Patients Suffering from Systemic Inflammatory Response Syndrome

The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane on the kinetics of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-lβ), and their inhibitors (soluble TNF receptors [sTNFrl, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflammatory response syndrome. Blood and plasma flow (Q_b, Q_p), sieving coefficient (SC), plasma and ultrafiltrate clearances (K_p, K_uf), and plasma extraction rates (ER_p) were calculated at different time points using standard formulas. No significant improvement of hemodynamics or gas exchange was noted following HF but a significant increase in serum bicarbonate occurred after 24 h (P < 0.05). TNFα was detected in plasma from all patients (153 ± 2.3 pg/mL [mean ± SEM]). None of the patients had detectable IL-1β levels. High levels of the TNF receptors (sTNFrl 20.338 ± 2.431 pg/mL; sTNFrII 17.839 ± 2.630 pg/mL) and IL-1Ra (19.775 ± 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrl/TNFα. ratio amounted to 269 ± 84.6 and the sTNFrII/TNFα ratio to 249 ± 91.8. Mean ultrafiltrate volume (V_uf) was 11.8 ± 0.4 L/day. Appreciable sieving of IL-1Ra (SC 0.45 ± 0.10), but not of the other cytokines, was noted (SC TNFα, sTNFrI, sTNFrII < 0.09). Despite minimal K_uf of TNFα, sTNFrI, and STNFrII (K_uf < 0.8 mL/min), appreciable K_p was noted, suggesting that membrane adsorption occurs (K_p ≈ 8 mL/min). There was a nonsignificant increase of the ratios between both TNF receptors and TNFα across the filter (sTNFrI/TNFα ratio [pre] 231 ± 37.9 versus [post] 312 ± 75.3); sTNFrII/TNFα ratio [pre] 211 ± 42.1 versus [post] 291 ± 79.3). Appreciable K_p of IL-1Ra was noted (K_p 17.3 ± 1.61 mL/min), which was only in part due to K_uf(4.0 ± 0.86 mL/min). There was a significant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 ± 2.282 versus [post] 16.637 ± 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only for IL-1Ra was significant extraction from plasma noted (ER_p 26 ± 6.0%). Plasma levels of TNFα, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF. In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane adsorption. Using low-volume HF (V_uf 12 L/day), no impact on cytokine plasma levels nor the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (>50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to be investigated.