不同复苏液对创伤失血性休克大鼠血浆及肺组织TNF-α、IL-6及MPO的影响

目的探讨大鼠创伤失血性休克复苏时使用25%白蛋白与乳酸林格液对早期肺损伤的影响及可能机制。方法45只SD大鼠随机分为3组,假手术(Sham)组、林格液(RL)组和白蛋白(ALB)组复苏后2h取血并处死动物取肺组织测定TNF-α、IL-6表达及髓过氧化酶(MPO)活性和肺湿/干重(肺W/D)比值。结果各实验组休克复苏2h后血浆及肺泡灌洗液TNF-α、IL-6表达以及肺组织MPO活性、肺W/D比值均较Sham组高(P<0.05);ALB组复苏后维持MAP80~90mmHg所需液体较RL组明显减少(P<0.05);ALB组复苏后血浆及肺泡灌洗液TNF-α、IL-6表达以及肺组织MPO活性、肺W/D比值均较RL组低(P<0.05)。结论大鼠创伤失血性休克时血浆及肺组织TNF-α、IL-6表达及MPO活性增高,白蛋白复苏较乳酸林格液复苏肺组织损伤减轻。     

Toll样受体4在失血性休克小鼠肺组织HO-1表达中的作用

目的 探讨Toll样受体4(TLR4)在失血性休克并发急性肺损伤(ALI)小鼠肺组织血红素加氧酶-1(HO-1)表达中的作用.方法 采用小鼠失血性休克复苏模型,48只TLR4基因突变型小鼠C3H/HeJ和野生型小鼠C3H/HeN随机分为2组:①假手术组;②失血休克复苏组.分别于失血性休克复苏后6 h、24 h和48 h取颈动脉血行血气分析,检测肺组织HO-1蛋白和mRNA的表达、肺组织IL-6含量及髓过氧化物酶(MPO)活性.采用方差分析进行数据统计.结果 失血休克复苏后24 h C3H/HeN和C3HL/HeJ的肺组织中HO-1 mRNA和蛋白含量的表达、IL-6含量、MPO活性与假手术组比较显著增加(P＜0.01或P＜0.05);与C3H/HeN鼠比较,休克复苏后24 h C3H/HeJ鼠的HO-1mRNA和蛋白含量、IL-6含量和MPO活性明显降低(P＜0.01或P＜0.05).C3HL/HeN鼠休克复苏后24 h并发ALI并且PaO2/FiO2＜300 mmHg.结论 TLR4受体激活在失血性休克致ALI肺组织HO-1的表达中扮演重要角色.     

乌司他丁对创伤失血性休克兔肺损伤的保护作用

目的 探讨乌司他丁对肺缺血-再灌注损伤的保护作用及其机制。方法 新西兰白兔30只,随 机分为假手术对照组、创伤失血性休克组和乌司他丁治疗组。动物模型用经股动脉放血使平均动脉压降至 (40±5)mm Hg(1 mm Hg=0.133 kPa).维持90 min后回输全部失血及等量乳酸林格液进行复苏。复苏后4 h 测定肺组织髓过氧化物酶(MPO)、肺泡灌洗液中中性粒细胞弹性蛋白酶(BALF-NE)活性、肺叶湿／干重比 及肺组织病理学改变。结果 休克组和乌司他丁治疗组MPO含量、BALF-NE活性以及湿／干重比均较假手 术对照组显著增高(P均<0.05),乌司他丁治疗组各指标均明显低于休克组(P均<0.05)。结论 蛋白酶抑 制剂乌司他丁在创伤失血性休克时能够抑制肺MPO和NE活性,降低肺组织湿／干重比,减轻缺血-再灌注 后的肺损伤。     

HES200溶液复苏失血性休克对肺损伤保护作用的实验研究

目的探讨羟乙基淀粉200/0．5（HES200）溶液复苏失血性休克对大鼠肺损伤保护作用及其机制。方法制作SD大鼠失血性休克模型，分别用HES200、羟乙基淀粉40溶液（HES40）、乳酸林格液（RL）复苏大鼠，观察复苏后1、2、4h动脉氧分压（PaO2）、血清TNF-α、肺组织核因子kBNF-kB）、细胞间粘附分子-1（ICAM-1）的表达、肺组织髓过氧化物酶（MPO）活性、肺组织湿干重比值（W／D）。结果失血性休克大鼠复苏后各生物学指标HES200组较其它液体复苏组低，肺损伤程度减轻。结论羟乙基淀粉200溶液通过减轻失血性休克大鼠复苏后炎症反应从而对肺损伤具有保护作用。     

肠系膜淋巴管结扎对失血性休克大鼠肺损伤的影响

目的观察结扎肠系膜淋巴管对不同时期重症失血性休克大鼠肺组织自由基、炎症介质的影响，探讨肠淋巴途径在休克大鼠急性肺损伤（ALI）中的作用。方法78只雄性Wistar大鼠被随机分为假手术组、休克组和结扎组。休克组与结扎组复制重症失血性休克模型。结扎组于休克复苏后行肠系膜淋巴管结扎术，于休克90min、液体复苏后0、1、3、6、12和24h各处死6只大鼠，制备肺组织匀浆，检测丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）以及髓过氧化物酶（MPO）活性。结果休克组大鼠输液复苏后各时间点肺组织匀浆MDA、TNF—α、IL-6以及MPO活性均有不同程度的升高，3～12h持续在较高水平，均显著高于假手术组，肺组织匀浆SOD活性显著低于假手术组（P〈0．05或P〈0．01）；结扎组输液复苏后3，6、12和24h肺组织匀浆MDA、TNF-α、IL-6以及MPO活性均显著低于休克组，SOD活性高于休克组（P〈0．05或P〈0．01）。结论肠系膜淋巴管结扎可干预重症失血性休克大鼠ALI，其机制与减少肺中性粒细胞扣押，降低TNF—α、IL-6、自由基释放与SOD消耗等因素有关。     

正丁酸钠对失血性休克大鼠肺部HMGB1 mRNA的调节

目的 研究正丁酸钠(sodium butyrate)对失血性休克大鼠肺部HMGB1 mRNA的影响.方法 由股动脉抽血建立失血性休克模型.30只动物随机分为假手术组、休克复苏组及正丁酸钠治疗组,于复苏后12 h处死动物.检测肺湿/干质量(W/D)比值、支气管肺泡灌洗液(BALF)中中性粒细胞(PMN)百分比和总蛋白浓度;测定肺组织髓过氧化物酶(MPO)活性、丙二醛(MDA)含量; RT-PCR法检测肺组织HMGB1 mRNA表达.结果 正丁酸钠组与休克复苏组相比,肺W/D、BALF中总蛋白含量及PMN百分比显著减少(P<0.05),肺组织MPO和MDA含量、肺组织HMGB1 mRNA表达明显降低(P<0.05).结论 正丁酸钠对失血性休克诱发的肺损伤有保护作用,可能与下调HMGB1 mRNA表达有关.     

聚合人脐带血红蛋白对复苏失血性休克大鼠肺组织的影响

目的探讨不同浓度聚合人脐带血红蛋白(PolyCHb)复苏对失血性休克大鼠肺组织的影响。方法建立Wistar大鼠失血性休克控压模型:将40只健康雄性Wistar大鼠随机均分为假手术(sham)组、生理盐水(对照)组、2%、4%及6%PolyCHb组(8只/组)。sham组:大鼠麻醉后仅行股动、静脉插管;后4组建立大鼠失血性休克控压模型,分别给予生理盐水、生理盐水加相应浓度的PolyCHb复苏。分别在大鼠放血前(基础值)、休克、液体回输后0 h(复苏后0 h)、6 h(复苏后6 h)观测各组大鼠平均动脉压(MAP)、动脉二氧化碳分压(PaCO_2)、肺氧合指数(PaO_2/FiO_2);复苏后6 h以放血法处死大鼠,收集支气管肺泡灌洗液(BALF),测定蛋白含量,取肺组织,测定湿/干重比(W/D)值,另取肺组织制备成10%的组织匀浆,测定丙二醛(MDA)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)的含量。结果 1)复苏后0 h,2%、4%、6%PolyCHb组与对照组的MAP(mmHg)为117.25±5.97 vs 132.00±5.98 vs 147.75±5.82 vs 101.13±6.15(P<0.05)。2)复苏后6 h,4%、6%PolyCHb组与对照组相比,MAP(mmHg)分别为114.75±5.26 vs 118.63±13.81 vs 88.38±8.00(P<0.05);2%、4%PolyCHb组和对照组的PaCO_2(mmHg)为37.62±3.62 vs 37.13±4.70 vs 25.38±4.10(P<0.05);2%PolyCHb组和对照组的PaO_2/FiO_2值为463.69±44.74 vs 403.57±59.73,BALF蛋白浓度值(mg/mL)为0.13±0.04 vs 0.23±0.06(P<0.05), MDA(nmol/mg protein)为1.17±0.11 vs 1.47±0.20,MPO(U/g tissue)为0.37±0.08 vs 0.76±0.23(均为P<0.05);2%、4%、6%PolyCHb组和对照组的SOD(U/mg protein)为2.04±0.27 vs 1.87±0.30 vs 1.63±0.10 vs 1.83±0.04(均为P>0.05)。结论具有携氧功能的低浓度PolyCHb可以减轻失血性休克大鼠肺损伤;但随着PolyCHb浓度的升高,大鼠氧化应激增强,反而加重肺损伤。     

HES200溶液复苏失血性休克对肺损伤保护作用的实验研究

目的探讨羟乙基淀粉200/0.5(HES200)溶液复苏失血性休克对大鼠肺损伤保护作用及其机制。方法制作SD大鼠失血性休克模型,分别用HES200、羟乙基淀粉40溶液(HES40)、乳酸林格液(RL)复苏大鼠,观察复苏后1、2、4 h动脉氧分压(PaO2)、血清TNF-α、肺组织核因子κB(NF-κB)、细胞间粘附分子-1(ICAM-1)的表达、肺组织髓过氧化物酶(MPO)活性、肺组织湿干重比值(W/D)。结果失血性休克大鼠复苏后各生物学指标HES200组较其它液体复苏组低,肺损伤程度减轻。结论羟乙基淀粉200溶液通过减轻失血性休克大鼠复苏后炎症反应从而对肺损伤具有保护作用。     

肠系膜淋巴管结扎对失血性休克大鼠肺组织一氧化氮及其表达的影响

目的 观察结扎肠系膜淋巴管对不同时期重症失血性休克大鼠肺组织一氧化氮（NO）及其表达的影响，探讨肠淋巴途径在休克大鼠急性肺损伤（ALI）中的作用。方法 雄性Wistar大鼠78只，按随机数字表法分为假手术组（n=6）、休克组（n=42）和结扎组（n=30）。休克组与结扎组复制重症失血性休克模型，结扎组于休克复苏后行肠系膜淋巴管结扎术；休克组于休克后90min、输液复苏后0h，休克组及结扎组于输液复苏后1、3、6、12和24h各时间点处死大鼠，制备肺组织匀浆，检测NO及其合酶的变化；用逆转录-聚合酶链反应（RT—PCR）测定各组大鼠肺组织诱生型一氧化氮合酶（iNOS）．mRNA表达。结果 休克组大鼠复苏后3h肺组织NO含量、NOS活性及iNOSmRNA表达开始升高，复苏后6～12h持续在较高水平，均显著高于假手术组、休克后90min及复苏后0h（P〈0．05或P〈0．01）；结扎组仅于3h和6h增高，且结扎组复苏后6、12和24h肺组织NO含量、NOS活性以及iNOSmRNA表达均显著低于休克组相同时间点（P〈0．05或P〈0．01）。结论 肠系膜淋巴管结扎可降低重症失血性休克大鼠肺组织NO生成及iNOSmRNA表达，从而减轻肺损伤。     

重组人脑利钠肽对创伤失血性休克导致肺损伤大鼠肺血管通透性的影响

目的:探讨重组人脑利钠肽(rhBNP)对创伤失血性休克导致急性肺损伤(ALI)大鼠的肺血管通透性的影响。方法:60只SD大鼠随机分为6组:假手术组、模型组、生理盐水组、rhBNP治疗1h组、rhBNP治疗12h组、rhBNP治疗24h组,每组10只大鼠。假手术组完成所有手术操作,但不放血和复苏;模型组完成所有手术操作,放血后给予复苏;生理盐水组在实验前经尾静脉注射无菌生理盐水(2.5ml/kg);rhBNP治疗1、12、24h组大鼠在实验前经尾静脉注射rhBNP(30μg/kg)治疗。各组于术后6h处死大鼠,采集标本,进行肺组织病理学检测及评分,计算肺组织湿/干(W/D)比重、肺水含量,测定肺泡灌洗液(BALF)蛋白含量、髓过氧化物酶(MPO)活性和肺组织匀浆伊文思蓝(EB)含量,并采用酶联免疫吸附测定法(ELISA)测定血清中IL-6和TNF-α水平。结果:肺组织病理学结果显示rhBNP治疗组的肺损伤程度轻于模型组,且rhBNP治疗1、12、24h组肺损伤病理学评分均低于模型组,其中rhBNP治疗12h组和rhBNP治疗24h组评分与模型组比较,差异有统计学意义(P0.05);rhBNP治疗12h组和rhBNP治疗24h组的BALF蛋白含量、肺W/D比值和肺水含量均明显低于模型组(P0.05,P0.01),且rhBNP治疗1、12、24h组的肺匀浆EB含量也明显低于模型组(P0.05,P0.01);rhBNP治疗1、12、24h组的肺匀浆MPO活力和血清IL-6、TNF-α水平明显低于模型组(P0.05,P0.01)。结论:rhBNP对创伤失血性休克导致的ALI有保护作用,可能是通过降低ALI时肺血管通透性来实现的。     

不同液体早期复苏在感染性休克患者的临床研究

目的:评价不同液体早期复苏对感染性休克患者EGDT达标、血乳酸清除率、APACHEⅡ评分和28d病死率的影响。方法:选取2005-10-2010-10收住ICU的感染性休克患者作为研究对象,随机分为高渗氯化钠羟乙基淀粉40溶液组(霍姆组)、3%高渗氯化钠组(高钠组)、羟乙基淀粉130/0.4氯化钠溶液组(万汶组)、生理盐水组(NS组)。分别经中心静脉通路输入相应的复苏液体,配合林格液对患者进行包括6h早期液体复苏在内的早期目标指导性治疗(EGDT)。分别记录各组患者在液体复苏前及复苏0、1、3和6h的心率(HR)、MAP、CVP、24h血乳酸值,并计算24h血乳酸清除率。观察EGDT达标情况、升压药物使用情况、复苏前及复苏72h的APACHEⅡ评分变化以及28d病死率。结果:①共收集符合条件标准的病例51例:霍姆组12例、高钠组10例、万汶组14例、NS组15例。各组患者的性别、年龄、MAP、CVP、HR、APACHEⅡ评分、血乳酸值比较,差异无统计学意义(均P>0.05);②研究液体用量在各组间比较,霍姆组与高钠组比较,差异无统计学意义;NS组、万汶组各自与其他3组比较,差异均有统计学意义(均P<0.05);复苏液体总量在各组间比较,NS组与其他3组比较,万汶组与霍姆组比较,差异均有统计学意义(均P<0.05);高钠组与霍姆组、高钠组和万汶组比较,差异均无统计学意义;林格液量在各组间比较,差异均无统计学意义;③随复苏时间延长,MAP逐渐升高,HR逐渐减慢,MAP、HR在不同时间点各组间比较,差异均无统计学意义(均P>0.05)。随复苏时间延长,CVP逐渐升高,在复苏1h、3h和6h时,霍姆组CVP均高于NS组,差异有统计学意义(均P<0.05);且在复苏1h时,霍姆组CVP高于万汶组,差异有统计学意义(P<0.01),高钠组CVP显著高于NS组(P<0.05);④复苏24h血乳酸值及其清除率在各组间比较,以及复苏后72hAPACHEⅡ评分在各组间比较,差异无统计学意义(均P>0.05);⑤各组患者使用升压药例数、使用升压药>3d例数及EGDT达标例数比较,差异均无统计学意义(均P>0.05)。感染性休克患者的整体病死率为45.10%(23/51),28d病死率在各组间比较,差异无统计学意义。结论:在感染性休克的早期液体复苏中,应用霍姆有利于提高CVP,但对需要应用升压药时间、EGDT达标、乳酸清除率、APACHEⅡ评分以及28d病死率并无无显著影响;对某些需限制性液体管理的患者,使用高渗氯化钠羟乙基淀粉40注射液或高渗盐水可以减少补液总量。     

Shock resuscitation with acupuncture: case report

A 77 year old aboriginal woman in an isolated village became drowsy and shocked. Poor weather conditions delayed the arrival of the medical and support team--the roads had been seriously destroyed by torrential rains and helicopter was the only means for delivering critical medical care and support. While waiting for the arrival of the helicopter, and in the absence of the necessary emergency medical equipment, the patient's condition deteriorated. Administration of persistent emergency acupuncture stimulation for 80 minutes helped maintain the patient's vital signs until successful transfer of the patient to hospital. She recovered without any complications of shock and was discharged six days later.     

A Minimal Model of the Single Capacitor Biphasic Defibrillation Waveform

A quantita tive model of the single capacitor biphasic defibrillation wave form is proposed. The primary hypothesis of this model is that the first phase leaves a residual charge on the membranes of the unsynchronized cells, which can then reinitiate fibrillation. The second phase diminishes this charge, reducing the potential for refibrillation. To suppress this potential refibrillation, a monophasic shock must be strong enoagh to synchronize a critical mass of nearly 100% of the myocytes. Since the biphasic waveform performs this protection function by removing the residual charge (with its second phase), its first phase may be of a lower strength than a monophasic shock of equivalent performance. A quantitative model was developed to calculate the residual membrane voltage, V_m, assuming a capacitive membrane being alternately charged and discharged by the first and second phases, respectively. It was further assumed that the amplitude of the first phase would be predicted by a minimum value plus a term proportional to V_m². The model was evaluated on the pooled data of three relevant published studies comparing biphasic waveforms. The model explained 79% of the variance in the first phase amplitude and predicted optimal durations for various defibrillator capacitances and electrode resistances. Assuming a first phase of opti mal duration, the optimal second phase duration appears to be about 2.5 msec for all capacitances and resistances now seen clinically. Conclusion: The effectiveness of the single capacitor biphasic waveform may be explained by the second phase "burping" of the deleterious residual charge of the first phase that, in turn, reduces the synchronization requirement and the amplitude requirements of the first phase.     

A Review of Methylene Blue Treatment for Cardiovascular Collapse

Background

Historically, methylene blue (MB) has been used for multiple purposes, including as an antidote for toxin-induced and hereditary methemoglobinemia, ifosfamide-induced encephalopathy, and ackee fruit and cyanide poisoning; as an aniline dye derivative, antimalarial agent, and antidepressant.

Discussion

Most recently, the use of MB has been advocated as a potential adjunct in the treatment of shock states. Our article reviews the role of MB in septic shock, anaphylactic shock, and toxin-induced shock. MB is proposed to increase blood pressure in these shock states by interfering with guanylate cyclase activity, and preventing cyclic guanosine monophosphate production and vasodilatation.

Summary

MB may be an adjunct in the treatment of septic shock, anaphylactic shock, and toxin-induced shock.     

Multiple Resuscitation Regimens in a Near-fatal Porcine Aortic Injury Hemorrhage Model

Objective: To compare early and delayed blood administrations in animals subjected to near-fatal hemorrhage in the presence of a vascular injury and resuscitated to different mean arterial pressures (MAPs).
Methods: Fifty-four immature swine with 4-mm infrarenal aortic tears were bled to a pulse pressure of 5 torr and then resuscitated (estimated blood loss 40 to 45 mL/kg). Groups I, II, and III were resuscitated with shed blood at a rate of 2 mL/kg/min, followed by normal saline at a rate of 6 mL/kg/min. Groups IV, V, and VI received the same fluids in reverse order. The fluids were infused intermittently to maintain MAPs of 40, 60, and 80 torr. The animals were observed for 60 minutes or until death.
Results: The animals resuscitated to a MAP of 80 torr experienced significantly higher intraperitoneal hemorrhage volumes and mortality than did the animals intentionally maintained hypotensive, regardless of whether blood or normal saline was administered first. There was no significant difference in mortality or hemorrhage volumes between any of the groups intentionally maintained hypotensive. The animals maintained at a MAP of 60 torr were significantly less acidotic than were the animals resuscitated with the same fluid regimen but to a MAP of 40 torr. Early blood administration also minimized the acidosis associated with hypotensive resuscitation.
Conclusion: In this model of near-fatal hemorrhage with a vascular injury, maintenance of the hypotensive state produced comparable improvements in one-hour survival and reductions in hemorrhage volume regardless of whether blood or saline was administered first. Although hypotensive resuscitation resulted in improved outcome, it was associated with significant acidosis. This effect was minimized with moderate rather than severe underresuscitation and early blood administration.     

失血性休克大鼠凝血因子的变化研究

本研究观察SD大鼠失血性休克过程中凝血因子的变化 ,探讨凝血连锁反应在休克发生、发展过程中的作用机制。制作大鼠失血性休克模型后 ,4 0只大鼠随机分为休克前组、休克 1、2、4、6、8、12和 2 4小时组。分别检测各组假血管性血友病因子 (vWF) ,凝血因子Ⅷ (FⅧ ) ,组织因子 (TF) ,D 二聚体 (D D) ,纤维蛋白原 (FIB)的血浆浓度及观察凝血酶原时间 (PT)、活化部分凝血酶原时间 (APTT)变化。结果表明 :与休克前比较 ,各休克组PT、APTT逐渐延长 ,于休克后 4 - 6小时显著延长 (P <0 .0 0 1) ,APTT平均 5 9.7秒 ,PT平均 30 .2秒。休克后 ,血浆D 二聚体显著增加 (P <0 .0 0 1) ,于休克 8小时达到峰值。血浆vWF、FⅧa、TF、FIB于休克早期增加 ,随着休克的发展 ,纤维蛋白原于休克 2小时开始明显下降 (P <0 .0 0 1) ,休克 12小时降至最低值。TF、vWF、FⅧa分别于休克 6小时、8小时开始明显下降 (P <0 .0 0 1或P <0 .0 5 )。凝血因子消耗比率 :FⅧ为 (86 .1± 1.8% ) ,纤维蛋白原为 (89.6± 0 .6 % ) ,假血管性血友病因子为 (5 5± 1.4 % ) ,组织因子为 (6 2± 2 .5 % ) ,其中 ,FⅧ、纤维蛋白原消耗比例较大。失血性休克时以外源性凝血途径激活为主 ,内源性凝血途径作用较小。纤维蛋白原和D 二聚体、PT、APTT可用     

Anaphylaxis

Background

Anaphylaxis is the quintessential critical illness in emergency medicine. Symptoms are rapid in onset and death can occur within minutes. Approximately 1500 patients die annually in the United States from this deadly disorder. It is imperative, therefore, that emergency care providers be able to diagnose and appropriately treat patients with anaphylaxis. Any delays in recognition or initiation of therapy can result in unnecessary increases in patient morbidity and mortality.

Discussion

Recent literature, including updated international anaphylaxis guidelines, has improved our understanding and management of this critical illness. Anaphylaxis is a multisystem disorder that can manifest signs and symptoms related to the cutaneous, respiratory, cardiovascular, and gastrointestinal systems. Epinephrine remains the drug of choice and should initially be administered intramuscularly, into the anterolateral thigh, as soon as the diagnosis is suspected. For patients unresponsive to repeated intramuscular injections, a continuous infusion of epinephrine should be started. Antihistamines and corticosteroids are second-line medications and should never be given in lieu of, or prior to, epinephrine. Aggressive fluid resuscitation should also be used to treat the intravascular volume depletion characteristic of anaphylaxis. Patient observation and disposition should be individualized, as there is no well-defined period of observation after resolution of signs and symptoms.

Conclusions

For patients with anaphylaxis, rapid and appropriate administration of epinephrine is critical for survival. Additional therapy, such as supplemental oxygen, intravenous fluids, antihistamines, and corticosteroids should not delay the administration of epinephrine.     

The potential role of thromboxane and prostacyclin in endotoxic and septic shock

The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated. Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2). Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock. In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied. Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time. An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy. Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions. In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis. These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls. These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock.