Lidocaine attenuates hyperoxic lung injury in rabbits

Background: High concentrations of oxygen acute lung injury. Neutrophils are thought to play a pivotal role in the pathogenesis of this lung injury through the release of oxygen radicals, neutral proteases, and lysosomal enzymes. Lidocaine has been shown to inhibit neutrophil function. We examined whether intravenous pretreatment with lidocaine attenuated acute lung injury induced by hyperoxia. Method: Twenty-seven anaesthetized male rabitts were allocated to receive one of three treatments (n = 9 for each group): ventilation with 100% oxygen for 36 h with and without lidocaine treatment, and ventilation with air for 36 h without lidocaine. In the lidocaine-treated group, a single intravenous lidocaine 2 mg/kg was administered immediately after the initiation of exposure to 100% oxygen; Results: Pure oxygen for 36 h caused no significant changes in haemodynamics, lung mechanics, or PaO₂/FiO₂ ratio. However, hyperoxia significantly increased the lung W/D weight ratio, the influx of neutrophils into the lung, and BALF concentrations of C3a, C5a, TNF-α, IL-1β, and albumin. Lidocaine attenuated these increases (W/D ratio: 5.7 vs 5.1, %PMN: 19.2% vs 1.6%, C3a: 62 ng/dl vs 14 ng/dl, C5a: 7.9 ng/dl vs 4.1 ng/dl, TNF-α: 25 fmol/ml vs 2.8 fmol/ml, IL-1β: 36 fmol/ml vs 2.2 fmol/ml, and albumin: 9.5 mg/dl vs 2.8 mg/dl, all: P <0.05). The chemiluminescence was increased in hyperoxic compared with in normoxic rabbits and lidocaine treatment attenuated the increase (opsonized zymosan stiluated: 3.7×10⁶ cpm vs 2.3×10⁶ cpm, P <0.05). Exposure to 100% oxygen caused extensive morphologic lung damage which was lessened by lidocaine (lung injury score (mean): 3 vs 4, P <0.05). Conclusion: These findings suggest that intravenous lidocaine has a prophylatic effect on initial hyperoxic lung injury (pulmonary vascular permeability, histopathological, and biochemical BALF changes) in rabbits. The effects of lidocaine on more severe lung injury (decreased oxygenation) caused by hyperoxia for 72 h deserve further study.     

乌司他丁对家兔油酸型肺损伤后血管外肺水肿和肺换气功能的影响

目的研究乌司他丁对家兔油酸型急性肺损伤（ALI）后血管外肺水肿和肺换气功能的影响。方法随机将20只大白兔分为两组，建立油酸型急性肺损伤模型，Ⅰ组于ALI前10min静脉滴注生理盐水5ml，Ⅱ组于ALI前10min静脉滴注乌司他丁1万u／kg。分别于ALI前后测定兔气道压（Paw）、氧合指数（OI）和呼吸指数（RI）；于ALI后2h取肺组织测定总肺水量（TLw）和肺血管外肺水量（EVLW）。结果ALI前两组Paw、OI和R1比较，差异无显著性（P〉0．05）；ALI后Ⅱ组Paw、0I和RI优于Ⅰ组（P〈0．05）；ALI后Ⅱ组TLW和EVLW低于Ⅰ组（P〈0．05）。结论预防性使用乌司他丁可以减轻兔油酸型急性肺损伤肺水肿，改善肺换气功能。     

自血光量子疗法对家兔脊髓损伤后超氧化物歧化酶的影响

目的：探讨自血光量子疗法治疗脊髓损伤的作用机制。方法４２只家兔随机分成对照组、损伤组和治疗组,用化学比色法分别测定各组血液和脊髓组织中超氧化物歧化酶（ＳＯＤ）活力。结果伤后不同时点血液和脊髓组织中ＳＯＤ活力与对照组比较均明显下降（Ｐ〈０．０１）;治疗组在采用自血光量子疗法治疗后,与相应时点损伤组比较均明显升高（Ｐ〈０．０１）。结论自血光量子疗法可以提高血液和脊髓组织中ＳＯＤ活性。     

Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain

Summary To study the involvement of free oxygen radicals of the blood-brain barrier (BBB) disruption during early reperfusion, we isolated the distal internal carotid artery, and the middle and anterior cerebral arteries via the transorbital approach in anesthetized rabbits. Using radiolabeled microspheres, regional cerebral blood flow (rCBF) was measured before, during and after 1-hour unilateral occlusion of these vessels. Fifty-five minutes after ischemia, animals received intravenous saline placebo (control), superoxide dismutase (SOD) at 8mg/kg=30000 U/kg, or weakened superoxide dismutase (wSOD) at 8mg/kg=30000 U/kg.Integrity of the BBB was assessed by leakage of Evan's Bluealbumin dye (EB-albumin dye), which was given at 15 minutes of reperfusion and allowed to circulate for an additional hour. In the control and wSOD-treated groups, rCBF decreased (26% and 40% of control, respectively) within the blue-tinted tissue of the occluded hemisphere during ischemia; hyperemia was observed during early reperfusion. In the control and wSOD-treated groups, EB-albumin dye leakage across the BBB increased 49% within the occluded hemisphere. However, within the SOD-treated group, the BBB showed minimal dye leakage even though rCBF of the occluded hemisphere (so-called blue-tinted tissue) decreased by 38% during ischemia. We conclude that 1-hour focal cerebral ischemia and reperfusion produce a vascular endothelial injury at the BBB. Since SOD administration showed significant protection, free-oxygen-radical production during early reperfusion is associated with break-down of the BBB to large molecules.     

The effect of superoxide dismutase and catalase on myocardial reperfusion injury in the isolated rat heart

This study was designed to evaluate the efficacy of superoxide dismutase (SOD) and catalase on ischemic and reperfusion injury in the isolated working rat heart. The temperature and duration of ischemia varied under three conditions: 1) at 37°C for 35 minutes, 2) at 28°C for 120 minutes and 3) at 20°C for 120 minutes. SOD (100 mg/L) and catalase (10 mg/L) were either added to St. Thomas' Hospital cardioplegic solution during ischemia (CP group) or to the reperfusion solution for 10 minutes after reflow (RS group). They were compared with a control group which received no free radical scavengers. The postischemic recovery ratio of cardiac functions were markedly superior to the values of the control group with a significant difference being noted in the CP and RS groups under ischemia at 37°C and 28°C. In the series done at 20°C, a significant improvement was seen in the RS group, and the CP group also showed better functional recovery rates compared with the control group, although the differences were not statistically significant. Thus, SOD and catalase added to the cardioplegic solution or reperfusion fluid demonstrated an excellent protective effect on the myocardium against ischemic or reperfusion injury in both hypothermic ischemia and normothermia.     

Effect of pulmonary artery pressure on extravascular lung water in an experimental model of acute lung injury

BACKGROUND: Lung edema can be influenced by hemodynamic changes in pulmonary circulation. The aim of this study was to evaluate, in an experimental model of acute lung injury, the effect on extravascular lung water (EVLW) of an increase in pulmonary artery pressure (Ppa) without changes in cardiac output and wedge pressure. METHODS: Lung edema was produced by an intravenous oleic acid infusion in mixed-breed pigs weighing 25-31 kg, which, after 20 min, were randomly assigned to a control group (100% FiO(2)) (n = 6) or a high Ppa group (21% FiO(2)) (n = 7). An increase in pulmonary artery pressure of at least 40% over baseline was produced in the high Ppa group by alveolar hypoxia. Hemodynamic, ventilatory and gas exchange parameters were collected at regular intervals. Pulmonary, wedge and capillary pressures were measured with a pulmonary artery catheter and the occlusion technique. EVLW was calculated gravimetrically. RESULTS: At 240 min, both gravimetric-measured EVLW and mean pulmonary artery pressures were significantly higher (P < 0.05) in high Ppa animals vs. controls (12.06 +/- 4.21 vs. 7.98 +/- 2.46 ml/kg and 39.0 +/- 1.3 vs. 26.6 +/- 4.7 mmHg, respectively). Cardiac output (6.8 +/- 2.5 vs. 7.3 +/- 1.3) and pulmonary wedge pressures (9.2 +/- 1.7 vs. 9.4 +/- 2.8 mmHg) were similar. A difference was detected in pulmonary capillary pressures [17.0 +/- 3.3 (high Ppa) vs. 13.8 +/- 2.7 mmHg (controls)] but did not reach statistical significance. CONCLUSIONS: In this model, an increase in pulmonary artery pressure by alveolar hypoxia produces an increase in extravascular lung water, probably related to changes in pulmonary capillary pressures.     

肺保护性通气对肝移植手术患者肺损伤血清生物标志物和炎性因子的影响

目的观察肺保护性通气对肝移植手术患者肺损伤血清生物标志物和炎性因子的影响,探讨其对肝移植术后急性肺损伤(acute lung injury,ALI)的影响。方法选择行原位肝移植术的终末期肝病患者60例,男42例,女18例,年龄21~62岁,体重43~80kg,ASAⅡ~Ⅳ级。随机分为肺保护性通气组(P组)和非肺保护性通气组(U组),每组30例。所有患者分别于麻醉后手术开始前(T_1)、机械通气3h(T_2)、新肝期2h(T_3)及新肝期4h(T_4)检测肺动脉血中肺损伤血清生物标志物和炎性因子的水平,包括克拉拉细胞分泌蛋白16(CC16)、表面活性蛋白(SP-D)及高级糖基化终末产物可溶性受体(sRAGE)、TNF-α、IL-6及IL-8;于T_1~T_4、术后2h(T_5)、拔管前(T_6)及术后2d(T_7)行桡动脉血血气分析。记录患者术后清醒时间、拔管时间、ICU停留时间及ALI的发生情况。结果与T_1时比较,T_2~T_4时两组血清CC16浓度明显升高(P0.05或P0.01);T_3时两组SPD、sRAGE、TNF-α、IL-6及IL-8浓度明显升高(P0.01);T_4时sRAGE、TNF-α、IL-6和IL-8浓度明显升高(P0.05或P0.01);T_2、T_5、T_6时两组氧合指数(OI)明显升高(P0.05或P0.01),T_4时P组明显降低(P0.01),T_3、T_4时U组明显降低(P0.01)。T_2、T_3时P组CC16浓度明显低于U组(P0.05或P0.01);T_3时P组OI明显高于U组(P0.05);P组术后拔管时间明显短于U组[(8.9±3.2)h vs(9.3±2.8)h,P0.05]。P组术后ALI 5例(16.6%),U组术后ALI 7例(23.3%),两组差异无统计学意义。结论肺保护性通气可改善肝移植手术患者的氧合指数,缩短拔管时间,减轻肺损伤。     

右美托咪定可减轻肺叶切除术中单肺通气所致肺损伤

目的探讨右美托咪定对肺叶切除术中单肺通气所致肺损伤的影响。方法选择2014年5月至2017年2月拟行肺叶切除术的肺癌患者64例,男38例,女26例,年龄42~75岁,ASAⅡ或Ⅲ级。根据不同治疗方式将患者分成两组,每组32例。麻醉诱导前20min,观察组泵注右美托咪定0.5μg·kg~(-1)·h~(-1),10min后改为0.2~0.5μg·kg~(-1)·h~(-1),对照组予以等容量生理盐水。检测麻醉诱导前10min(T_0)、单肺通气即刻(T_1)、单肺通气60min(T2)、单肺通气90min(T_3)、术后24h(T_4)的全血中性粒细胞(PMN)计数,血清髓过氧化物酶(MPO)、黄嘌呤氧化酶(XOD)活性,肺内分流率(Qs/Qt),以及T_0~T_3时血管内皮生长因子(VEGF)和一氧化氮(NO)浓度。结果与T_0时比较,T_2~T_4时两组PMN计数明显增多,MPO和XOD活性明显升高(P0.05),但观察组明显低于对照组(P0.05)。与T_0时比较,T_2、T_3时两组血清VEGF浓度明显升高,但T_3时观察组明显低于对照组(P0.05)。T_2、T_3时观察组血清NO浓度明显高于对照组(P0.05)。结论右美托咪定能减少患者肺部炎症反应,减轻单肺通气所致缺血-再灌注损伤,且降低了患者机体氧化应激程度,从而对肺起到保护作用。     

浅低温对急性肺损伤肺保护的研究进展

急性肺损伤发病机制尚未完全阐明,目前在临床上无特效治疗方法,病死率较高。浅低温能降低机体代谢,减轻肺负担,防治呼吸机相关性肺损伤。另一方面,浅低温还能抑制中性粒细胞浸润、减少氧自由基和细胞因子释放。减少细胞凋亡、血栓形成以及降低毛细血管通透性等减轻了肺损伤。     

利多卡因减轻内毒素诱导兔肺损伤炎症反应的实验研究

静脉注射内毒素引起的急性肺损伤与临床脓毒血症引起的急性肺损伤相似，是全身的过度炎症反应引起的急性损伤。肺由于其组织结构及功能的特殊性，往往成为受累最先及最严重的一个器官。近年，大量的动物及体外实验证明，利多卡因具有抑制中性粒细胞黏附、趋化，抑制氧自由基和蛋白水解酶释放，稳定细胞膜，调节细胞因子和抑制过度的炎症反应等作用。动物实验已经证实利多卡因预防性及打击后早期给药可以减轻多种因素诱发急性肺损伤的程度（包括高氧、盐酸吸入、胰酶及蛋白酶诱导、内毒素诱导及缺血再灌注损伤等）。但利多卡因剂量与减轻急性肺损伤程度的关系尚不清楚。本研究探讨利多卡因是否能减轻内毒素诱导兔肺部的炎症反应，最终减轻肺损伤及量效关系。     

乌司他丁联合地塞米松对内毒素所致兔急性肺损伤的保护作用

目的 探讨乌司他丁联合地塞米松对内毒素所致兔急性肺损伤的保护作用及其机制。方法 新西兰大白兔40只,随机均分为内毒素组（L组）、乌司他丁组（U组）、地塞米松组（D组）、乌司他丁联合地塞米松组（T组）、对照组（C组）。除C组外,其他组均经耳缘静脉给予内毒素600μg／kg,U、D、T组在给予内毒素同时静注乌司他丁100000U／kg或／和地塞米松5mg／kg。4h后测定血清肿瘤坏死因子α（TNF-α）及一氧化氮（NO）水平,行动脉血气分析,取肺组织观察大体标本形态和光镜下的组织病理形态,测定肺组织湿／干重量比值（W／D）、髓过氧化物酶（MPO）活性、脂质过氧化产物丙二醛（MDA）及超氧化物歧化酶（SOD）活性。结果 光镜下见C组肺组织学正常,L组肺间质弥漫性出血,肺泡腔内可见大量粒细胞聚集、浸润,并可见弥漫性肺泡间隔增厚,而U、D、T组上述病理表现明显减轻。与L组比较,U、D、T组兔肺组织湿／干重量比、MPO、MDA以及血清TNF_a和NO水平明显降低、SOD活性明显增强、动脉血气明显改善;T组较U、D组在某些指标上改善更为显著。结论 乌司他丁和地塞米松对内毒素所致兔急性肺损伤均有保护作用,两者联用则保护作用更为显著,该作用与两者减少炎性介质和氧自由基的释放、抑制酶联反应有关。     

Effect of superoxide dismutase on haematologic parameters and urinary changes after burn injury in rats

Summary This study was designed to examine the possible benefits that superoxide dismutase (SOD), a free radical scavenger, could induce upon some of the hematologic and urinary alterations occurring during the burn shock syndrome. The experiment was conducted by comparing two groups of rats treated with SOD and saline solution respectively, immediately after inducing a scald burn injury. Statistically significant differences were observed between the two groups in the mean increases of hematocrit and total hematic hemoglobin concentration 15 min postburn (p < 0.05) and in the presence or absence of urinary pigments (p < 0.001) 60 min postburn. These results demonstrate the role of oxygen free radicals in the physiopathology of the first stages of burn shock syndrome.     

肺保护性通气策略联合右美托咪定对胸腔镜肺癌根治术患者的肺保护作用

目的观察肺保护性通气策略联合右美托咪定对胸腔镜肺癌根治术患者炎症反应及术后肺部并发症的影响。方法选择择期行胸腔镜肺癌根治术的患者40例,男23例,女17例,年龄40～64岁,BMI 20～25 kg/m~2,ASAⅠ或Ⅱ级,随机分为两组:肺保护性通气策略组(P组)和肺保护性通气策略联合右美托咪定组(DP组)。DP组于麻醉诱导前10 min静脉泵注右美托咪定负荷量0.5μg/kg(10 min泵注完毕),随后以0.6μg·kg~(-1)·h~(-1)持续泵注至手术结束;P组以等容量生理盐水持续静脉泵注。双肺通气及单肺通气期间所有患者均采用相同的通气策略:V_T 6 ml/kg,FiO_2 70%,PEEP 5cmH_2O。分别在麻醉诱导前(T_0)、单肺通气前即刻(T_1)、单肺通气1 h(T_2)、单肺通气2 h(T_3)、术后2 h(T_4)、术后24 h(T_5)检测血清TNF-α、IL-6和MPO含量;记录术后肺部并发症情况。结果与P组比较,T_2—T_5时DP组TNF-α、IL-6、MPO含量明显降低(P0.05)。P组有2例(10%)肺部并发症。结论肺保护性通气策略联合右美托咪定用于胸腔镜肺癌根治术能够进一步减轻术中炎症反应,可能有助于减少术后肺部并发症的发生。     

Effect of ventilatory rate on airway cytokine levels and lung injury

BACKGROUND: Controversy exists regarding the effect of large-volume mechanical ventilation (MV), as a sole stimulus, on the pulmonary cytokine milieu. We used a well described experimental model of ventilator-induced lung injury (VILI) to examine the impact of large volume ventilation on pulmonary cytokines in vivo and to study the effect of respiratory rate (RR) variation on these levels. MATERIALS AND METHODS: Sixty rats (410 +/- 47 g) were randomized to: 1) non ventilated control; 2) V(t) = 40 ml/kg, RR = 40 bpm; 3) V(t) = 40 ml/kg, RR = 20 bpm; 4) V(t) = 7 ml/kg, RR = 40 bpm; or 5) V(t) = 7 ml/kg, RR = 20 bpm. After 1 h of MV, bronchoalveolar lavage (BAL) and serum were collected. BAL was analyzed for urea, protein, lactate dehydrogenase (LDH), tumor necrosis factor (TNF)alpha and interleukin (IL)-6. Epithelial lining fluid volume (ELF) was calculated. RESULTS: Regardless of RR, animals ventilated at 7 ml/kg did not differ from control in any outcome. In contrast, MV at 40 ml/kg V(t) with 40 bpm produced lung injury characterized by significant elevations of BAL TNFalpha, IL-6, protein, ELF, and LDH. At 40 ml/kg V(t), RR reduction (20 bpm) significantly reduced all injury measures. CONCLUSION: This study confirms that large-volume MV, as a sole stimulus, produces lung injury and cytokine release. Whereas increasing RR at low V(t) has little impact on injury parameters, RR reduction under VILI-promoting conditions significantly limits lung injury.     

Small dose of exogenous surfactant combined with partial liquid ventilation in experimental acute lung injury: effects on gas exchange, haemodynamics, lung mechanics, and lung pathology

A combination of exogenous surfactant and partial liquid ventilation(PLV) with perfluorocarbons should enhance gas exchange, improverespiratory mechanics and reduce tissue damage of the lung inacute lung injury (ALI). We used a small dose of exogenous surfactantwith and without PLV in an experimental model of ALI and studiedthe effects on gas exchange, haemodynamics, lung mechanics,and lung pathology. ALI was induced by repeated lavages (Pa_O2/FI_O2less than 13 kPa) in 24 anaesthesized, tracheotomized and mechanicallyventilated (FI_O2 1.0) juvenile pigs. They were treated randomlywith either a single intratracheal dose of surfactant (50 mgkg^–1, Curosurf^®, Serono AG, München, Germany)(SURF-group, n=8), a single intratracheal dose of surfactant(50 mg kg^–1, Curosurf^®) followed by PLV with 30 mlkg^–1 of perfluorocarbon (PF 5080, 3M, Germany) (SURF-PLV-group,n=8) or no further intervention (controls, n=8). Pulmonary gasexchange, respiratory mechanics, and haemodynamics were measuredhourly for a 6 h period. In the SURF-group, the intrapulmonaryright-to-left shunt (Q^·S/Q^·T) decreased significantlyfrom mean 51 (SEM 5)% after lavage to 12 (2)%, and Pa_O2 increasedsignificantly from 8.1 (0.7) to 61.2 (4.7) kPa compared withcontrols and compared with the SURF-PLV-group (P<0.05). Inthe SURF-PLV-group, Q^·S/Q^·T decreased significantlyfrom 54 (3)% after induction of ALI to 26 (3)% and Pa_O2 increasedsignificantly from 7.2 (0.5) to 30.8 (5.0) kPa compared withcontrols (P<0.05). Static compliance of the respiratory system(C_RS), significantly improved in the SURF-PLV-group comparedwith controls (P<0.05). Upon histological examination, theSURF-group revealed the lowest total injury score compared withcontrols and the SURF-PLV-group (P<0.05). We conclude thatin this experimental model of ALI, treatment with a small doseof exogenous surfactant improves pulmonary gas exchange andreduces the lung injury more effectively than the combined treatmentof a small dose of exogenous surfactant and PLV. Br J Anaesth 2001; 87: 593–601     

Antioxidant effects of maslinic acid in livers,hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function

Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5?h equilibration for 4 h of 1 h control, 1.5?h treatment and 1.5?h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18?h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na⁺ outputs and additionally the FE_Na indicating that at least part of the overall reduction in Na⁺ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus.     

氯胺酮对家兔内毒素性急性肺损伤的影响

目的研究氯胺酮对家兔内毒素(ET)性急性肺损伤(ALI)的影响。方法采用两次注射脂多糖(LPS)的方法复制家兔ALI模型。动物随机分为四组,每组6只:氯胺酮1组(K1组)、氯胺酮2组(K2组)、LPS组(阳性对照)、生理盐水(NS)组(阴性对照),第2次LPS注射后8 h结束实验,测定以下指标变化:支气管肺泡灌洗液(BALF)中白细胞和肺泡上皮细胞计数、肺水含量、肺通透指数(LPI)、肺组织髓过氧化物酶(MPO)含量、肺组织病理。结果LPS组BALF中白细胞和肺泡上皮细胞数量、肺水含量、LPI和肺MPO含量均较NS组明显上升(P<0.01)。NS组肺病理检查正常;LPS组双肺明显肿胀,表面有点片状出血,轻挤切面有水肿液溢出,镜下有明显肺不张和肺泡萎陷,肺间质增厚,内有大量白细胞浸润,肺血管淤血;K1组与K2组前述各指标和病理变化的程度轻于LPS组,其中K2组又明显好于K1组。结论氯胺酮可减轻LPS注射后家兔ALI程度。