Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation

Background

Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction.

Methods and results

Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC + NTG10 mcg/kg/min, HBOC + NTG20 mcg/kg/min, HBOC + NTG40 mcg/kg/min, Hetastarch (HES), HES + NTG20 mcg/kg/min, NTG20 mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP = 94 ± 33 mmHg), mean pulmonary artery pressure (MPAP = 29 ± 11 mmHg) and systemic vascular resistance (SVR = 2684 ± 871 dyn s/cm⁵) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC + 40 mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP = 59 ± 23 mmHg, MPAP = 18 ± 7 mmHg, and SVR = 1827 ± 511 dyn s/cm⁵), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation.

Conclusion

Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.     

产兔与非孕兔休克复苏后肺损伤的比较研究

目的 探讨产兔和非孕兔失血性休克复苏后急性肺损伤的差异.方法 将18只新西兰兔按随机数字表法分为产兔组和非孕兔组,每组9只.采用颈动脉放血致失血性休克1h,乳酸林格液复苏持续3h建立失血性休克复苏模型.分别于产前期、产后期(休克前期,0h)、休克期末(1 h)、复苏期间(2.5 h)以及复苏期末(4 h)5个时间点采血测定肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10);复苏期持续3h后处死动物,取肺组织检测丙二醛(MDA)、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、干/湿重比值(D/W),以及核转录因子-κB(NF-κB)活性和细胞间黏附分子-1(ICAM-1)mRNA表达.结果 产兔产前期血清TNF-α(ng/L)、IL-10(ng/L)含量与非孕兔差异无统计学意义(TNF-α:87.6±6.8比83.2±5.3;IL-10:44.9±3.9比42.7±3.4,均P＞0.05);休克前期TNF-α水平显著增高(102.5±8.1比87.6±6.8,P＜0.05).产兔与非孕兔休克1h后TNF-α、IL-10均升高;各复苏时期产兔TNF-α水平明显高于非孕兔(1 h:230.0±14.9比202.0±10.1,2.5 h:290.0±18.6比236.0±14.4,4 h:265.0±15.9比217.0±12.8,均P＜0.05),而IL-10水平明显低于非孕兔(1 h:104.3±6.9比135.0±7.8,2.5 h:146.8±9.4比178.3±11.7,4 h:126.0±7.9比165.8±9.6,均P＜0.05).休克复苏后产兔肺组织MDA、MPO、D/W比值、NF-κB活性和ICAM-1 mRNA表达均显著高于非孕兔[MDA(nmol/mg):52.6±5.9比39.4±4.7,MPO(U/mg):4.62±0.85比3.26±0.62,D/W比值:0.186±0.025比0.143±0.016,NF-κB(A值):0.89±0.27比0.46±0.15,ICAM-1mRNA:4.6±1.2比2.5±0.7,均P＜0.05];而SOD(U/mg)水平较低(47.8±6.7比63.5±8.2,P＜0.05).结论 分娩可致产兔血清炎症因子TNF-α显著升高,失血性休克复苏后产兔出现肺组织炎症损伤较非孕兔更为严重,炎症因子的差异可能是导致休克复苏后炎症应答差异的原因之一.     

Cimetidine kinetics during resuscitation from burn shock

Severely burned patients suffer from rapidly changing metabolic and hemodynamic abnormalities that could alter drug kinetics. The kinetics of cimetidine, commonly used in the prophylaxis of acute stress erosions, were studied during fluid resuscitation of 11 patients with mean burn sizes of 45% total body surface area. Six patients were studied after the completion of fluid resuscitation. Total clearance, steady-state volume of distribution, and cimetidine t1/2 did not change between the early period after burn and after fluid resuscitation, but before the completion of fluid resuscitation patients had lower renal and greater nonrenal cimetidine clearance than after resuscitation. The increase in nonrenal cimetidine clearance resulted in decreased urinary recovery of unchanged drug, 50.7 +/- 14% during fluid resuscitation and 81.0% +/- 6% after resuscitation.     

Metformin attenuates ventilator-induced lung injury

ABSTRACT: INTRODUCTION: Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury. METHODS: Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF. RESULTS: High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation. CONCLUSIONS: Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.     

Acadesine during fluid resuscitation from shock and abdominal sepsis

OBJECTIVE: To determine properties of acadesine, the prototype adenosine regulating agent, in an experimental model in which abdominal sepsis is superimposed onto hemorrhagic shock. DESIGN: Randomized, blinded animal study. SETTING: University-based animal research facility. SUBJECTS: Twenty-eight anesthetized mongrel pigs (35.5 +/- 1.1 kg). INTERVENTIONS: The cecum was ligated and punctured to produce abdominal sepsis. To produce hemorrhagic shock, 45% to 47% of the estimated blood volume was withdrawn. After 1 hr, shed blood plus supplemental crystalloid (twice the shed blood volume) plus either acadesine (5 mg/kg bolus + 1 mg/kg x 60 min, n = 10) or its vehicle (n = 10) was administered. All animals were awakened and observed for 48 hrs. At 48 hrs, cardiac function, bacterial cultures from the septic focus, and inflammatory changes in the abdomen were quantified. MEASUREMENTS AND MAIN RESULTS: After resuscitation with acadesine vs. vehicle, we observed the following: a) arterial blood pressure and cardiac filling pressures were similar but cardiac index, systemic oxygen delivery, and systemic oxygen consumption were increased; b) plasma lactate was higher, systemic vascular resistance was lower, but ileal mucosal blood flow was not measurably altered; c) lipopolysaccharide-evoked tumor necrosis factor production in whole blood ex vivo was reduced; d) in those animals that survived 48 hrs (10/10 vs. 8/10), sepsis-induced cardiac depression, amount of free intraperitoneal fluid, extra abscess inflammatory reaction, abscess wall formation, abscess bacterial counts, and peritoneal bacterial counts, were all similar, but blood bacterial counts were higher. CONCLUSIONS: Fluid resuscitation with acadesine produced no adverse hemodynamic consequences and probably improved washout of metabolites from the reperfused microcirculation in sites other than the small intestine or heart. Taken together, these observations suggest that adenosine regulating agents might have therapeutic potential during fluid resuscitation from trauma. However, at least in these extreme conditions, the acute salutary effects of acadesine were probably overwhelmed by polymicrobial sepsis. Further studies must determine whether supplemental adjuvants to boost host defense during recovery from trauma will optimize adenosine-based resuscitation solutions.     

高压氧对失血性休克复苏后炎症反应的影响

目的观察高压氧对大白鼠失血性休克复苏后炎症反应的影响并探讨其作用机制。方法Wistar大鼠随机分为三组：高压氧治疗组、休克组和对照组。建立大鼠失血性休克模型,自体血和生理盐水复苏后应用2．0绝对大气压高压氧治疗,于休克前、休克后、复苏后和复苏后24h取血检测血红细胞SOD、血浆卧限a、血浆iNOS值,并进行统计学（one-way ANOVA plus SNK）分析。观察复苏后24h大鼠肝、肠、肺组织病理改变并进行病理损伤评分。结果复苏后24h高压氧治疗组血红细胞SOD值高于休克组,高压氧治疗组血浆iNOS值和TNFoa值低于休克组,差异具有统计学意义（P〈0．05）。病理损伤评分：高压氧治疗组病理损伤与休克组相比减轻,差异具有统计学意义（P〈0．05）。结论 高压氧可能通过增强机体清除活性氧和自由基、阻止炎症介质的产生,进而减轻大鼠失血性休克复苏后的炎症反应和组织脏器的病理损伤。     

两种复苏溶液对创伤失血性休克大鼠早期肺损伤的影响

目的　探讨创伤失血性休克后小容量复苏与传统等渗溶液复苏对早期肺损伤的影响及其可能机制。方法　 4 8只雄性SD大鼠随机分为 3组 .sham组、LRH组和HSH组 ,每组 1 6只。LRH组和HSH组动物复制创伤失血性休克模型并维持低血压 (MAP 4 0mmHg) 6 0min ,其后 5min内开始复苏 (LRH组以 3倍于总失血量的乳酸林格氏液 +5ml/kg体重的 6 %贺斯 ;HSH组以 5ml kg体重的 7 5 %氯化钠 +6 %贺斯复合液 )。sham组仅行动、静脉置管。分别于复苏后 1h和 2 4h两个时间点处死半数动物 ,测定肺组织MPO活性、肺水含量及光镜下肺组织形态学改变 ;休克前及复苏后各时间点分别采血测定中性粒细胞表面CDllb表达水平 (流式细胞术 )。结果　LRH组肺组织MPO活性、肺水含量和中性粒细胞CDllb表达水平均比同一时间点HSH组和sham组高 (P <0 0 5或P <0 0 1 ) ;HSH组肺损伤评分比LRH组低 (P <0 0 5或P <0 0 1 ) ;LRH组复苏后 1h可见肺泡间质增宽 ,肺微血管周围有较多炎症细胞聚集 ,在复苏后 2 4h上述改变更加明显 ,而且可见肺泡间质水肿 ,肺泡腔渗出。HSH组复苏后 1h肺组织结构基本正常 ,在复苏后 2 4h有少量炎症细胞浸润。结论　创伤失血性休克采用LRH复苏后早期即出现明显肺损伤 ,而用HSH复苏对早期肺损伤具有显著的保护作用 ;LRH复     

Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shock/resuscitation in rats

Aim of the study

Haemorrhagic shock and subsequent resuscitation induce acute lung injury. We elucidated whether bilateral lower limb ischemic pre-conditioning (IP) could mitigate lung injury in haemorrhagic shock/resuscitation rats. The role of heme oxygenase-1 (HO-1) was also elucidated.

Method

Adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus IP, or HS plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Sham groups were employed simultaneously. For pre-conditioning, 3 cycles of limb IP (10 min ischemia followed by 10 min reperfusion) were performed immediately before haemorrhagic shock. Haemorrhagic shock (mean arterial pressure: 40-45 mmHg) was induced by blood drawing and maintained for 120 min. SnPP was injected 5 min before resuscitation. Shed blood/saline mixtures were re-infused to achieve resuscitation. After monitoring for another 8 h, rats were sacrificed. Arterial blood gas and alveolar-arterial oxygen difference (lung function index), histology, polymorphonuclear leukocytes/alveoli ratio (leukocyte infiltration index), wet/dry weight ratio (water content index), inflammatory molecules (e.g., chemokine, cytokine, prostaglandin E₂), and malondialdehyde (lipid peroxidation index) assays were preformed.

Results

Haemorrhagic shock/resuscitation induced significant lung function alterations and significant increases in leukocyte infiltration, water content, inflammation, and lipid peroxidation in lungs. Histological analysis confirmed that haemorrhagic shock/resuscitation caused marked lung injury. Limb IP significantly mitigated the adverse effects of haemorrhagic shock/resuscitation. Moreover, the protective effects of limb IP were reversed by SnPP.

Conclusions

Limb IP mitigates lung injury in haemorrhagic shock/resuscitation rats. The mechanisms may involve HO-1.     

Inhaled nitric oxide reduces lung edema during fluid resuscitation in ovine acute lung injury

OBJECTIVE: Fluid resuscitation in sepsis-related lung injury is limited by aggravation of pulmonary edema. Hypovolemia, however, may compromise tissue perfusion and contribute to organ dysfunction. We hypothesized that inhaled nitric oxide would reduce edema formation during fluid therapy. DESIGN AND SETTING: Prospective laboratory investigation in a university research laboratory. PARTICIPANTS: Eighteen chronically instrumented sheep. INTERVENTIONS: The animals were randomly assigned to one of three groups and received endotoxin (S. typhi, 10 ng kg(-1) min(-1)) for 30 h. After 24 h the sheep were anesthetized (ketamine/midazolam), mechanically ventilated with oxygen, and received 0.1 ml kg(-1) oleic acid: oxy group (n=6), an infusion of Ringer's lactate was restricted to 1 ml kg(-1) h(-1); fluid/oxy group (n=6), a bolus of 10 ml kg(-1) Ringer's lactate plus 10 ml kg(-1) h(-1) was given; fluid/NO group (n=6), the sheep were treated as in the fluid/oxy group, except that they inhaled nitric oxide (20 ppm). MEASUREMENTS AND RESULTS: The extravascular lung water index was measured using thermodye dilution. Oleic acid increased extravascular lung water, impaired oxygenation, and reduced cardiac index at 26 h in all groups. After 30 h the extravascular lung water in the fluid/NO group was not higher than in the oxy group and significantly than in the fluid/oxy group. While cardiac index returned to the level of sepsis baseline in fluid/NO and fluid/oxy, it was reduced in the oxy group after 30 h. There were no significant differences in cardiac index between groups. CONCLUSIONS: Inhaled nitric oxide may be an option for reducing edema formation secondary to fluid resuscitation in acute lung injury.     

抑制一氧化氮合成对急性肺损伤炎症反应的调节作用

目的 :研究抑制一氧化氮对脂多糖 (LPS)诱导肺损伤炎症反应的影响。方法 :ELISA检测TNFα、IL 1β、IL 6和IL 10浓度 ,Griess法测定亚硝酸盐浓度。肺湿干重比反映小鼠肺损伤程度。结果 :小鼠腹腔注射LPS 2 0mg/kg后 ,血浆及肺泡灌洗液 (BALF)中TNFα、IL 1β、IL 6、IL 10和亚硝酸盐浓度显著升高。LPS注射前 30min给予地塞米松 70mg/kg,血浆TNFα、IL 1β、IL 6、IL 10及亚硝酸盐浓度明显降低 ,而BALF中IL 1β、IL 6、IL 10浓度明显降低。给予一氧化氮合酶抑制剂S 硫酸甲基异硫脲 (SMT) 85mg/kg ,血浆IL 1β和IL 6明显升高 ,BALF中TNFα明显升高 ,而IL 1β、IL 6和IL 10无明显改变。与LPS组相比 ,地塞米松组肺湿干重比明显降低 ,而SMT组相反。结论 :抑制一氧化氮引起促炎性细胞因子释放增加 ,并加重肺损伤。     

舌下CO2分压检测在休克救治中的应用

目的应用一种临床新技术——舌下CO2分压检测,通过对局部灌流的检测最终达到对休克以及全身血液灌注状态的了解。方法采用回顾性分析失血性休克患者的休克指数、动脉血乳酸（IAC）和舌下CO2分压。结果通过对正常组（A组）、轻中度休克组（B组）和重度休克组（C组）患者的检测发现,A、B、C三组之间的舌下CO2分压值差异有统计学意义。结论舌下CO2分压具有检测方便,对休克患者能量化组织灌流不足的严重性,从而指导现场急救或临床中对休克的救治工作。     

Simvastatin attenuates ventilator-induced lung injury in mice

Introduction

Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative/nitrosative stress play important roles in the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors are largely undetermined.

Methods

Twenty-four chronically instrumented sheep were subjected to inhalation of 48 breaths of cotton smoke and instillation of live Pseudomonas aeruginosa into both lungs and were euthanized at 4, 8, 12, 18, and 24 hours post-injury. Additional sheep received sham injury and were euthanized after 24 hrs (control). All animals were mechanically ventilated and fluid resuscitated. Lung tissue was obtained at the respective time points for the measurement of neuronal, endothelial, and inducible NOS (nNOS, eNOS, iNOS) mRNA and their protein expression, calcium-dependent and -independent NOS activity, 3-nitrotyrosine (3-NT), and poly(ADP-ribose) (PAR) protein expression.

Results

The injury induced severe pulmonary dysfunction as indicated by a progressive decline in oxygenation index and concomitant increase in pulmonary shunt fraction. These changes were associated with an early and transient increase in eNOS and an early and profound increase in iNOS expression, while expression of nNOS remained unchanged. Both 3-NT, a marker of protein nitration, and PAR, an indicator of DNA damage, increased early but only transiently.

Conclusions

Identification of the time course of the described pathogenetic factors provides important additional information on the pulmonary response to ALI and sepsis in the ovine model. This information may be crucial for future studies, especially when considering the timing of novel treatment strategies including selective inhibition of NOS isoforms, modulation of peroxynitrite, and PARP.     

Hyperbaric oxygen attenuates lipopolysaccharide-induced acute lung injury

OBJECTIVES: To study the effect of hyperbaric oxygen therapy in alleviating acute lung injury induced by lipopolysaccharide (LPS) in rats.DESIGN AND INTERVENTIONS: The rats received an intraperitoneal injection of LPS (15 mg/kg). Animals were either breathing air at 1 ATA or subjected to hyperbaric oxygen (HBO(2)) therapy. The HBO(2) therapy was carried out in a hyperbaric chamber at a pressure of 3 ATA for 90 min. In another two groups, LPS-treated rats also received intraperitoneal injection of N(omega)-nitro-L-arginine (LNAME, 25 mg/kg) or L-N(6)-(iminoethyl)lysine (LNIL, 10 ml/kg). Another two groups of LPS-treated rats were subjected to HBO(2) exposure after the injection of L-NAME or L-NIL.MEASUREMENTS AND MAIN RESULTS: The bronchoalveolar lavage (BAL) was done into the left lung at 7.5 h after intraperitoneal injection of LPS. Parts of the right lung were excised for myeloperoxidase measurement, whereas the rest was collected for wet/dry ratio determination. LPS significantly increased the nitrite/nitrate (NO(x)(-)) concentration (34.4+/-15.7 vs 4.5+/-3.1 microM), LDH activity (66+/-17 vs 46+/-15 mAbs/min), and protein concentration (373+/-119 vs 180+/-90 mg/l) in the BAL fluid. Treatment with HBO(2) immediately after the injection of LPS enhanced the increase of NO(x)(-) production, but reduced the LDH and protein in BAL fluid to the control levels. Pretreatment with either L-NAME or L-NIL abolished the increase of NO(x)(-) in the BAL fluid and further elevated the LDH level and protein concentration.CONCLUSION: Our results suggested that HBO(2) alleviates the LPS-induced acute lung injury, which may be related to the enhancement of nitric oxide production.     

Inhaled milrinone attenuates experimental acute lung injury

Purpose  To test whether inhalation of the phosphodiesterase 3 inhibitor milrinone may attenuate experimental acute lung injury (ALI). Methods  In rats, ALI was induced by infusion of oleic acid (OA). After 30 min, milrinone was inhaled either as single dose, or repeatedly in 30 min intervals. In mice, ALI was induced by intratracheal instillation of hydrochloric acid, followed by a single milrinone inhalation. Results  Four hours after OA infusion, ALI was evident as lung inflammation, protein-rich edema and hypoxemia. A single inhalation of milrinone attenuated the increase in lung wet-to-dry weight ratio and myeloperoxidase activity, and reduced protein concentration, neutrophil counts and TNF-α levels in bronchoalveolar lavage. This effect was further pronounced when milrinone was repeatedly inhaled. In mice with acid-induced ALI, milrinone attenuated hypoxemia and prevented the increase in lung myeloperoxidase activity. Conclusions  Inhalation of aerosolized milrinone may present a novel therapeutic strategy for the treatment of ALI.     

Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received beta-glucan or beta-glucan + beta-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. beta-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the beta-glucan inhibitor abrogated beta-glucan's survival benefit (50%). After CLP, plasma TNF-alpha, IL-1beta, and IL-6 concentrations were increased in control animals. When beta-glucan was administered, it completely blocked the elevation of TNF-alpha, IL-1beta, and IL-6. Administration of beta-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with beta-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.     

不同复苏液对失血性休克大鼠肺组织超微结构的影响

目的 探讨不同复苏液对失血性休克大鼠肺组织超微结构的影响.方法 40只SD大鼠被随机分为对照组、休克组、林格组和羟乙基淀粉130/0.4(万汶)组,每组10只.按Lamson法快速放血使平均动脉压降至40 mm Hg(1 mm Hg=0.133 kPa)维持1 h制备失血性休克大鼠模型;制模后林格组给予乳酸林格液复苏,万汶组给予万汶加乳酸林格液复苏.复苏2 h后取血并处死大鼠取肺脏.观察组织病理学改变和电镜超微结构改变.结果 光镜下观察休克组大鼠肺泡壁破坏严重;林格组可见大鼠肺泡问质增宽,肺泡壁和血管壁有轻度水肿;万汶组大鼠肺泡结构接近正常.电镜下观察休克组大鼠肺组织超微结构呈明显损伤改变;林格组和万汶组大鼠肺组织超微结构损伤较轻,但林格组同时出现间质水肿现象;对照组大鼠肺组织超微结构正常.结论 大鼠发生失血性休克后,肺组织超微结构发生改变.单纯使用乳酸林格液治疗失血性休克可能会加重肺部损伤,但联合使用万汶能减少内皮细胞损伤,减轻炎性细胞浸润.