不同液体复苏对失血性休克-内毒素二次打击大鼠急性肺损伤的影响

目的 比较不同液体复苏对失血性休克-内毒素二次打击大鼠急性肺损伤的影响.方法 60只雄性SD大鼠,体重250～280 g,随机分为5组(n=12):假手术组(S组)、失血性休克-内毒素组(SL组)、乳酸钠林格氏液组(LR组)、7.5%氯化钠组(HS组)和羟乙基淀粉(HES)130/0.4组(HES组).分为院前期(90 min)、院内复苏期(1 h)和复苏后观察期(3.5 h).院前期:SL组、LR组、HS组和HES组颈总动脉放血建立失血性休克模型(维持MAP 35～45 mm Hg 60 min)后,气管内注射内毒素2mg/kg,同时断尾,注射内毒素后即刻分别经30 min静脉输注3倍放血量的乳酸钠林格氏液、7.5%氯化钠4ml/kg和等放血量的6%HES 130/0.4;院内复苏期:结扎尾部断端止血,在1 h内回输全部放出的血液及等放血量的0.9%氯化钠;复苏后观察期3.5 h时采集动脉血样,进行血气分析,计算肺组织湿/干重量比(W/D)和肺通透指数(PPI),测定肺泡灌洗液(BALF)蛋白浓度和肺组织AQP-1 mRNA和AQP-5mRNA表达水平,光镜下观察肺组织病理学结果,记录大鼠存活情况.结果 与SL组和LR组比较,HS组和HES组MAP、pH值、PaO2和SaO2升高,血乳酸浓度、BE、W/D、PPI和BALF蛋白浓度降低,HS组肺组织AQP-1 mRNA表达上调,HES组肺组织AQP-1 mRNA和AQP-5 mRNA表达上调,大鼠存活率升高(P＜0.05或0.01);与HS组比较,HES组W/D降低,AQP-5 mRNA表达上调,大鼠存活率升高(P＜0.05),肺组织损伤程度减轻.结论 6%HES 130/0.4和7.5%氯化钠可减轻失血性休克-内毒素二次打击大鼠急性肺损伤,6%HES 130/0.4的效果更好,其机制与抑制AQP-1和(或)AQP-5表达下调有关;而乳酸钠林格氏液对其无效.     

P38MAPK信号通路在失血性休克复苏诱发急性肺损伤小鼠HO-1表达上调中的作用

目的 探讨p38分裂原激活蛋白激酶(p38MAPK)信号通路在失血性休克复苏诱发急性肺损伤小鼠血红素加氧酶1(HO-1)表达上调中的作用.方法 SPF级野生型小鼠C3H/HeN32只32只,10～12周龄,体重20～25 g,随机分为4组(n=8),假手术组(S组):只进行手术操作;失血性休克复苏组(HSR组):股动脉放血,至MAP为40 mm Hg,通过放血和回输血液维持MAP 35～45mmHg,60 min后回输全部血液和等失血量的乳酸钠林格氏液复苏;FR167653组(FR组):静脉注射p38MAPK抑制剂FR167653 5 mg/kg;FR+HSR组:于放血前30 min静脉注射FR167653 5 mg/kg.复苏后6 h处死小鼠,取肺组织,观察病理学结果,并进行病理学评分,计算肺湿/干重比,检测肺组织髓过氧化物酶(MPO)、IL-10、IL-6和HO-1水平以及p38MAPK的激活水平.结果 与S组比较,HSR组肺组织病理学评分、肺湿/干重比、MPO、IL-6、IL-10、HO-1和p38MAPK的激活水平升高,HSR+FR组肺组织病理学评分、肺湿/干重比和HO-1表达水平升高(P＜0.01),FR组上述指标差异无统计学意义(P＞0.05);与HSR组比较,HSR+FR组肺组织病理学评分、肺湿/干重比、MPO、IL-6、IL-10、HO-1和p38 MAPK激活水平降低(P＜0.01).结论 p38MAPK信号通路介导了失血性休克复苏诱发急性肺损伤小鼠HO-1的表达上调.     

高渗氯化钠羟乙基淀粉注射液输注对急性颅内高压伴失血性休克犬脑组织病理学及氧自由基的影响

目的 观察高渗氯化钠羟乙基淀粉40注射液(HSH)在犬急性颅内高压伴失血性休克模型中恢复循环血容量、减轻脑组织水肿和降低脑组织氧自由基含量的作用.方法 健康杂种犬20只,采用硬膜外球囊注水和动脉放血的方法复制急性颅内高压伴失血性休克模型.动物随机分为羟乙基淀粉溶液组(HES组),乳酸盐林格液组(RL组),7.5%氯化钠溶液组(HS组)和高渗氯化钠羟乙基淀粉40注射液组(HSH组),在休克后1 h分别输入相应液体.监测平均动脉压(MAP)、中心静脉压(CVP)、心率(HR)、颅内压(ICP),检测脑组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力,脑组织标本行病理学检查.结果 复苏后4组液体均能有效地升高MAP(P<0.05),但HES组和RL组的ICP上升明显(P<0.05),复苏后2 h,HS组的MAP开始下降(P<0.05).至复苏后4 h,仅HSH组能维持理想的MAP及较低的ICP,HSH组脑组织氧自由基含量较其他组明显减少(P<0.05).病理学检查显示复苏后4 h,HSH组的脑组织损伤较其他组轻.结论 高渗氯化钠羟乙基淀粉40注射液可有效地复苏失血性休克,降低ICP及氧自由基的生成,减轻脑组织缺血/再灌注的损伤.     

高氧液对失血性休克家兔循环和血清丙二醛水平的影响

目的 观察高氧液对失血性休克家兔血液动力学的影响。方法 家兔休克90min后回输放血总量1／3的血液，同时分别输注复方乳酸钠(对照组，n=10)及高氧液(治疗组，n=10)。结果 再灌注后治疗组MAP迅速上长，于再灌注后3h显著高于对照组，CVP及HR较快恢复至休克前的水平，而血清丙二醛(MDA)呈下降趋势；对照组再灌注后MDA显著上升，而MAP进行性下降。结论 高氧液能迅速逆转失血性休克血液动力学改变，有效防治休克。     

高渗盐复苏消除肠系膜淋巴液对中性粒细胞的预激

失血性休克后,中性粒细胞(PMN)被预激是继发多器官功能衰竭(MOF)的前兆。近年来的研究发现,失血性休克动物用林格液(LR)复苏后其肠系膜淋巴液对PMN仍有预激潜能并可导致肺损伤,而用高渗盐水(HTS)复苏者其肺脏受到保护,因此进一步     

家猪失血性休克容量复苏时内皮素和一氧化氮的变化及其与肾功能的关系

目的 探讨家猪失血性休克容量复苏时血浆内皮素(ET)和一氧化氮(NO)的变化及其与肾功能的关系.方法 雄性家猪14头,体重14～17 kg,随机分为2组(n=7):假手术组(S组)和失血性休克容量复苏组(HS-VR组).HS-VR组经股动脉放血建立失血性休克模型[通过放血和回输放出的血液维持平均动脉压(MAP)35～45 mm Hg,持续90 min],然后回输全部放出的血液及等容量的复方乳酸钠林格氏液进行容量复苏.S组除不放血及容量复苏,其他操作同HS-VR组.分别于放血前(基础值)、失血性休克模型制备成功时(T1)、容量复苏结束时(T2)、容量复苏结束后30 min(T3)、60 min(T4)、120 min(T5)、240 min(T6)时记录MAP、心率(HR)、中心静脉压(CVP)、肺动脉压(PAP)、肺动脉楔压(PCWP)和心输出量(CO),并于上述时点采集血样,测定血浆ET、NO、尿素氮(BUN)和肌酐(Cr)浓度,并计算ET/NO比值,ET/NO比值分别与血浆BUN、Cr浓度进行直线相关分析.结果 与S组比较,T1时HS-VR组MAP、PAP、CVP和CO降低,HR增加,血浆ET、BUN和cr浓度升高,ET/NO比值升高,T2时PAP和CVP升高,T4时HR降低,T6时PAP和ET/NO比值降低,T4-6时血浆NO浓度升高(P<0.05或0.01);HS-VR组血浆ET/NO比值与BUN、Cr浓度呈正相关.结论 容量复苏可纠正ET与ND功能失衡,改善失血性休克家猪肾功能.     

高渗晶-胶混合液、等渗晶体溶液和全血抗犬失血性休克效果的比较

目的 比较高渗晶-胶混合液、等渗晶体溶液和全血对失血性休克犬的血流动力学和全身氧供状态的影响。方法 18只犬麻醉后气管内插管,自主呼吸,经股动脉放血至平均动脉压6.7 kpa,维持1 h。然后分别以乳酸林格氏液(LR)、全血(WB)和7.5％氯化钠 10％羟乙基淀粉混合液(HHS)进行抗休克治疗,比较其效果。结果HHS使休克犬血流动力学参数和全身氧供恢复至休克前水平所需液体量和时间显著少于LR和WB,且作用维持时间长(P<0.05)。结论 失血性休克早期应用小容量HHS可改善血流动力学和全身氧供状态。     

四种不同复合液对急性颅内高压伴失血性休克兔复苏的效果及其机制

目的 探讨4种不同复合液体对急性颅内高压伴失血性休克兔复苏的效果及机制.方法 家兔24只,随机分为甘露醇羟乙基淀粉组( MT+ HS)组、甘露醇低分子右旋糖酐组(MT+HD)组、7.5％高渗氯化钠羟乙基淀粉组(HSH)组、7.5％高渗氯化钠低分子右旋糖酐组(HSD)组,每组6只,采用硬膜外球囊注水和动脉放血的方法复制急性颅内高压伴失血性休克模型,分别于8个不同时点采集平均动脉压(MAP)、中心静脉压(CVP)、颅内压(ICP)、脑灌注压(CPP)数据.结果 4组复合液均能提高MAP,HSH组在复苏后20 min达到峰值,反应速度最快,提高MAP的平均幅度分别为(29.4±2.1)、(27.9±3.4)、(41.0±2.2)、(40.6±1.6) mm Hg(1 mm Hg =0.133 kPa),提高幅度差异有统计学意义(P＜0.05);4组复合液提高CVP值的幅度均接近于(3.0±1.4) cm H2O(1 cm H2O =0.098 kPa),提高幅度差异无统计学意义(P＞0.05);4组复合液均能在不同时段将ICP值降至基础值水平(7.3±1.6) mmHg,将CPP值升至基础值水平(69.6±6.8)mm Hg,峰值水平差异无统计学意义(P＞0.05).结论 4组复合液均有纠正休克和降低颅内压的效果,HSH维持效用的时间最持久,复苏效果最明显.     

利多卡因对失血性休克大鼠肺损伤的保护作用

目的 探讨利多卡因对失血性休克大鼠肺损伤的保护作用。方法 80只雄性Wistar大鼠建立失血性休克模型后,随机分为四组,假手术组(Ⅰ组,n=8)、休克组(Ⅱ组,n=8)、生理盐水组(Ⅲ组,n=32)、利多卡因组(Ⅳ组,n=32)。Ⅰ组于假手术后,Ⅱ组于休克60 min,Ⅲ、Ⅳ组分别于复苏开始后2、4、8、12 h,测定中性粒细胞(PMNs)表面粘附分子CD11b/CD18表达、肺组织中髓过氧化物酶(MPO)活性,并采用光镜和透射电镜观察肺组织的病理学改变。结果 与Ⅰ组比较,Ⅲ组、Ⅳ组复苏后各时点PMNs表面CD11b/CD18表达均升高(P<0.01),Ⅱ组差异无显著性(P>0.01),Ⅱ组、Ⅲ组、Ⅳ组复苏后各时点肺组织中MPO活性升高(P<0.05或0.01)。与Ⅲ组比较,Ⅳ组复苏后同一时点、Ⅰ组、Ⅱ组PMNs表面CD11b/CD18表达及肺组织中MPO活性降低(P<0.01)。结论 小剂量利多卡因可以抑制失血性休克大鼠PMNs表面CD11b/CD18的表达,减少PMNs在肺组织中的浸润,从而减轻肺损伤。     

高晶体-高胶体渗透压混合液对失血性休克时大鼠脑血流及脑组织含水量的影响

目的 比较HHS和乳酸林格氏平衡液（LR）对大鼠失血性休克模型脑血流和脑组织含水量的影响。方法 14只大鼠随机分为2组,采用动脉放血的方法复制失血性休克模型。分别在休克后输入LR或HHS。于休克前、休克后、容量复苏后即刻和30min测其脑血流量和脑组织含水量。脑血流是采用^99mTc标记同位素法测定,脑组织含水量用烘干前后称重的方法测定。结果 容量复苏后即刻,二级动物脑血流量增加（P＜0．05）。30min后,LR组的脑血流量降低,明显低于复苏后即刻的脑血流量和同时刻HHS组的脑血流量（P＜0．05）。HHS组则无明显减少。HHS组脑组织含水量在复苏后降低（P＜0．05）,LR组动物的脑组织含水量则增加（P＜0．05）。结论 小容量HHS可增加脑出流量、减轻休克后脑组织水肿。LR不能有效地恢复脑血流量,并且可加重脑组织水肿。     

Hypertonic saline resuscitation abrogates neutrophil priming by mesenteric lymph

OBJECTIVE: Neutrophil (PMN) priming after hemorrhagic shock is predictive of the subsequent development of multiple organ failure, but the mechanism remains unknown. Recently, we and others have demonstrated that mesenteric lymph from shock animals resuscitated with lactated Ringer's solution (LR) is not only a potent PMN priming agent but also causes lung injury. Work by others has shown that resuscitation with hypertonic saline (HTS) protects animals from lung injury after hemorrhagic shock. Therefore, we hypothesize that resuscitation with HTS will abolish PMN priming by postshock mesenteric lymph. METHODS: After mesenteric lymph duct catheterization, male rats underwent hemorrhagic shock (mean arterial pressure of 40 mm Hg for 90 minutes) and resuscitation with shed blood plus either LR (2x volume of shed blood) or 4 mL/kg of 7% HTS (isonatremic). Priming for superoxide by PMN was measured after fMLP (1 microM) activation. RESULTS: Shock significantly decreased mesenteric lymph flow from preshock levels in both groups. LR resuscitation produced significantly more mesenteric lymph than HTS resuscitation. Mesenteric lymph from LR animals primed PMN for superoxide production, whereas, HTS eliminated this priming. CONCLUSION: HTS not only decreases postshock mesenteric lymph production, it eliminates PMN priming by mesenteric lymph, suggesting a mechanism for the beneficial effects of HTS resuscitation.     

内源性一氧化碳/一氧化氮在失血性休克中的作用

目的探讨内源性一氧化碳(CO)／一氧化氮(NO)在失血性休克(HS)中的变化及其意义。方法14头体重为14～17kg的健康雄性家猪，随机分成两组：失血性休克组(H组)和对照组(C组)，每组7头。H组按照Wigger’s改良法制作失血性休克模型，经股动脉快速放血使MAP降至40mmHg，维持90min，然后回输血液及等量的复方乳酸钠。C组处理同实验组，但不放血。各组分别在休克前、休克末、复苏末、复苏后0．5、1、2、4h分别记录MAP、HR、PAP、PCWP、CVP，测定股动脉血、肺动脉血中CO含量，以及动脉血乳酸盐浓度和血浆中N0水平。结果H组休克后MAP、PAP和CVP降低而HR升高，PCWP无显著变化。休克后肺动脉血CO水平逐渐增加，复苏后2h显著高于休克前，并高于C组，此后逐渐下降；股动脉血CO水平无显著变化；血浆NO水平在休克后逐渐升高，复苏后1h显著高于休克前和对照组水平。乳酸盐浓度在失血后显著升高，休克末达峰值，显著高于休克前和C组，以后逐渐下降，至4h恢复到休克前水平。结论HS后肺动脉血中CO水平增加，与NO共同参与HS的病理生理过程。     

Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%) resuscitation

Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury. Sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6) or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial pressure (ICP) were followed. At the end of resuscitation brain water content was determined in injured and uninjured hemispheres. No differences were detected in cardiovascular parameters; however, ICPs were lower in animals resuscitated with HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05). Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1; p less than 0.05). No differences were detected in the injured hemispheres. We conclude that hypertonic saline abolishes increases in ICP seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood-brain barrier is still intact. Hypertonic saline may prove useful in the early management of multiple trauma patients.     

Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression.

BACKGROUND: In a two-hit model of hemorrhagic shock and lipopolysaccharide (LPS), we previously showed that hypertonic saline (HTS) resuscitation reduced lung sequestration of neutrophils and the accompanying injury. This effect was partially attributed to suppressed expression of the surface adhesion molecule CD11b. This study investigates the duration of this protective effect after a single HTS dose and the usefulness of repeated infusions. MATERIAL AND METHODS: The previous two-hit rodent model was used. Neutrophil lung sequestration was measured by bronchoalveolar fluid cell count. CD11b expression was followed by flow cytometry. In vitro studies used isolated human neutrophils. RESULTS: Eighteen hours following resuscitation, the protective effect of HTS was lost. At this time, LPS caused an increase in both neutrophil lung sequestration and CD11b expression, regardless of the resuscitation regimen used. A second infusion of HTS prevented these changes and restored the lung protection observed earlier. In vitro studies showed that the duration of hypertonic pretreatment is an important determinant of cell responsiveness under the isotonic conditions: Four but not 2 h hypertonic exposure was able to prevent upregulation of CD11b induced by LPS added immediately after reestablishing isotonicity. CONCLUSIONS: This study demonstrates that HTS resuscitation lessens lung neutrophil sequestration and CD11b surface expression induced by LPS. This protective effect is transient but can be restored by a second HTS infusion suggesting that maintenance of beneficial effect necessitates repeated HTS addition. The reversibility ensures rapid modulation of neutrophil functions, thereby preventing acute tissue damage without causing long-lasting immunosuppression.     

高渗氯化钠高氧液对失血性休克家兔血乳酸和动脉血气的影响

目的:观察高渗氯化钠高氧液对失血性休克家兔动脉血气和血乳酸值的影响，评价其对失血性休克的早期救治效果。方法:制备高渗氯化钠溶液(HS)、生理盐水高氧液（NSO）和高渗氯化钠高氧液(HSO)。30只雄性家兔制备失血性休克模型［于10min内使平均动脉压（MAP）降至40mmHg（1mmHg＝0.133kPa），维持60min］，随机分为NSO，HS，HSO组3个治疗组。分别按6mL/kg剂量5min内静脉输入NSO,HS和HSO。记录休克前后及给药后心率（HR）、呼吸（RR）、MAP及尿滴（UD），测定休克前、休克60min，给药后30，60，120min时血乳酸（BL）和动脉血气值。最后观察尸肺，测定肺系数。结果:HS和HSO组均显著地改善MAP，HR和UD，降低BL，改善代谢性酸中毒,肺系数明显低于NSO组。HSO与NSO及HS比较，能更显著地降低血BL，提高动脉血氧饱和度（SaO2）和动脉血氧分压（PaO2）。结论:HSO较HS和NSO能更显著地降低血BL,提高SaO2和PaO2，对失血性休克的早期救治具有较高的使用价值。     

The role of lung innervation in the hemodynamic response to hypertonic sodium chloride solutions in hemorrhagic shock

The role of pulmonary innervation in the genesis of hemodynamic responses to hypertonic salt solutions was assessed in an animal model of total lung denervation by total division of the pulmonary hilum followed by reimplantation of the organ. This was performed in 10 mongrel dogs (weighing 12 to 20 kg) randomly assigned to two groups: group I (five dogs) was comprised of animals with catheters placed in the pulmonary artery of the denervated lung; group II (five dogs) was comprised of animals with catheters placed in the pulmonary artery of the intact lung; a control group (group III) (five dogs) was submitted to a sham thoracotomy with catheters inserted in either pulmonary artery. On the seventh postoperative day the mean arterial pressure (MAP) was monitored and severe hemorrhagic shock (MAP = 40 mm Hg) was produced in all animals. After 30 minutes of shock the shed blood was discarded and 5% of the shed volume (+/- 2 ml/kg) was infused through the pulmonary catheter in the form of a hypertonic NaCl solution (2400 mosm/L). MAP continued to be measured for the 30 minutes following the infusion period. A significant rise of MAP was uniformly observed in animals of groups II and III. In group I low elevations of MAP were observed during the infusion period, followed by a return to shock levels on discontinuation of the infusion. The results suggest that selective lung denervation abolished the beneficial cardiovascular effects of hypertonic NaCl infusion during resuscitation from severe hemorrhagic shock without affecting the plasma osmolality pattern.