抑制一氧化氮合成对犬感染性休克的影响

目的：探讨一氧化氮在感染性休克中的作用机制,及抑制ＮＯ合成的治疗学意义。方法：１０只健康杂种狗予戊巴比妥麻醉,大肠杆菌内毒素６０μｇ．ｋｇ＾－１．ｈ＾－１×３０ｍｉｎ静脉滴注,继以生理盐水（ＮＳ）１５ｍｌ．ｋｇ＾－１．ｈ＾－１维持。随机分成两组,组Ⅰ,组Ⅱ在ＬＰＳ开始注射后６０ｍｉｎ分别单剂注射ＮＳ３０ｍｌ,ＮＳ３０ｍｌ＋Ｌ－硝基精 氨酸２０ｍｇ．ｊｇ＾－１。观察血液动力学,氧动力学,尿ＮＯ３／Ｎ     

感染性休克与失血性休克早期内皮素和一氧化氮变化规律的比较

研究发现,感染性休克与失血性休克时一组对血管作用相反的指标内皮素(ET)和一氧化氮(NO)都升高,并对组织均有损害作用[1-3].至于这两种休克早期ET和NO的变化规律有何异同,尚未见报道.为此,本研究比较这两种休克早期ET和NO的变化规律,为临床早期有针对性地干预休克,防治ET、NO引起的器官损伤提供实验证据.     

内毒素休克血浆一氧化氮的变化及其意义

为了探讨一氧化氮与内毒素休克的关系，应用脂多糖建立兔内毒素休克模型，然后应用Ｎ－硝基左旋精氨酸治疗，分别观察治疗前后血压，血浆ＮＯ的变化，结果发现内毒素休克时，血浆ＮＯ２升高，静注Ｌ－ＮＮＡ后，休克大白兔血压升高，血浆ＮＯ下降。提示内毒素休克时，机体内ＮＯ产生增加并与低血压有关，Ｌ－ＮＮＡ可能具有治疗内毒素休克的意义，值得进一步的研究。     

硝基精氨酸—赖氨酸三肽对感染性休克大鼠血压的影响并机制探讨

目的 用合成的硝基精氨酸－赖氨酸三肽（以下简称新化合物）在大鼠感染性休克模型上检测其对血压的影响，并对其作用机制作一探讨。方法：１．盲肠结扎穿孔法（ＣＬＰ）建立大鼠感染性休克模型，检测新化合物对血压、血清一氧化氮（ＮＯ）的影响。２．大鼠腹腔巨噬细胞培养，检测新化合物对诱导型一氧化氮合酶（ｃＮＯＳ）的抑制程度。结果：１．新化合物（０．０１ｍｍｏｌ／ｋｇ）明显升高感染性休克大鼠血压至接近假手术组水平；     

硝基精氨酸-赖氨酸三肽对感染性休克大鼠血压的影响并机制探讨

目的　用合成的硝基精氨酸 赖氨酸三肽 (以下简称新化合物 )在大鼠感染性休克模型上检测其对血压的影响 ,并对其作用机制作一探讨。方法 :1.盲肠结扎穿孔法 (CLP)建立大鼠感染性休克模型 ,检测新化合物对血压、血清一氧化氮 (NO)的影响。 2 .大鼠腹腔巨噬细胞培养 ,检测新化合物对诱导型一氧化氮合酶 (iNOS)的抑制程度。 3 .大鼠离体主动脉条孵育 ,检测新化合物对结构型一氧化氮合酶 (cNOS)的抑制程度。结果 :1.新化合物 ( 0 0 1mmol/kg)明显升高感染性休克大鼠血压至接近假手术组水平 ;注射新化合物、NG- 硝基 左旋精氨酸(L NNA)可使大鼠血清NO水平下降 ,新化合物较L NNA作用更明显。 2 .新化合物 ( 10 4mol/L)可显著抑制大鼠腹腔巨噬细胞产生NO (P <0 0 1) ,较L NNA作用增强 (P <0 0 1)。 3 .与L NNA相比 ,新化合物 ( 1 5× 10 4mol/L)对大鼠主动脉壁cNOS的抑制程度减小 (P <0 0 5)。结论 :硝基精氨酸 赖氨酸三肽对感染性休克大鼠血压有优越的升高作用 ,其机制在于选择性地抑制iN OS     

内毒素休克血浆一氧化氮的变化及其意义

为了探讨一氧比氮与内毒素休克的关系,应用脂多糖建立兔内毒素休克模型,然后应用N-哨基左旋精氨酸治疗,分别观察治疗前后血压,血浆NO的变化.结果发现内毒素休克时,血浆NO浓度升高,静注L-NNA后,休克大白兔血压升高,血浆NO下降.提示内毒素休克时,机体内NO产生增加并与低血压有关,L-NNA可能具有治疗内毒素休克的意义,值得进一步研究.     

精氨酸加压素对感染性休克兔胃肠灌注的影响

目的评价精氨酸加压素(arginine vasopressin,AVP)对感染性休克兔胃黏膜二氧化碳分压与动脉血二氧化碳分压差(P(g-a)CO2)及肠系膜上动脉血流量的影响。方法日本大白兔麻醉后压力控制通气,静脉注入内毒素复制感染性休克模型,达到休克标准后随机分成2组:单纯补液组(对照组)和精氨酸加压素组(AVP组)。对照组按20ml/(kg.h)输注生理盐水,AVP组除按20ml/(kg.h)输注生理盐水外,持续输注AVP0.001IU/(kg.min)。连续监测平均动脉压、心率、心脏指数和肠系膜上动脉血流指数,每10min测定胃黏膜二氧化碳分压一次,每小时测定血红蛋白浓度、动静脉血气分析、动脉血乳酸。结果静脉注射内毒素后,两组平均动脉压、心脏指数及肠系膜血流量指数均明显下降,但P(g-a)CO2和乳酸明显增加。分组治疗2h后,两组平均动脉压、心脏指数及肠系膜上动脉血流流指数均上升,除AVP组平均动脉压升高较对照组明显[(72±4)mmHgvs(65±3)mmHg,t=3.7,P<0.01)外,心脏指数[(181±11)ml/kgvs(187±5)ml/kg,t=1.5,P>0.05]及肠系膜上动脉血流指数[(14.5±1.9)ml/kgvs(16.1±1.4)ml/kg,t=1.9,P>0.05)]的变化两组差异无统计学意义。AVP组的P(g-a)CO2较对照组高,但差异亦无显著性统计学意义[(30±3)mmHgvs(27±4)mmHg,t=1.3,P>0.05)]。结论实验结果显示,感染性休克兔进行容量复苏时,加用小剂量精氨酸加压素有利于恢复平均动脉压,对P(g-a)CO2及肠系膜上动脉血流量无显著影响。     

一氧化氮合酶抑制剂对大鼠创伤性休克的治疗作用

目的：评价选择性诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)和非选择性一氧化氮合酶抑制剂L—硝基精氨酸甲酯(L—NAME)对创伤性休克的治疗效果。方法：30只SD大鼠制作创伤性休克动物模型。双侧股骨干砸伤后并经股动脉放血至平均动脉压(MAP)35—45mmHg(1mmHg＝0．133kPa)，维持30min，然后回输失血和等量的林格氏液。随机分为休克组(10只)、AG组(10只，复苏时静脉注射AG8mg／kg)、L—NAME组(10只，复苏时静脉注射L—NAME 8mg／kg)，观察休克前后血浆一氧化氮(NO)浓度的动态变化，观察24h大鼠存活率，24h后留取肺、肝、肾、小肠组织，观察病理改变。结果：大鼠创伤性休克后，血浆NO水平明显高于休克前；AG组动物复苏后血浆NO的水平明显降低，各脏器的病理损害亦显著减轻，存活率明显提高：L—NAME组动物复苏后血浆NO的水平也明显降低，各脏器的病理损害无明显变化，存活率无明显提高。结论：NO在创伤性休克的病理发展过程中起着重要作用，应用AG有助于创伤性休克的纠正，而L—NAME能降低NO的水平，但对休克的预后无明显改善。     

一氧化氮与内毒素休克关系的实验研究

为了评价一氧化氮（NO）在内毒素休克中的作用，应用脂多糖建立兔内毒素休克模型，然后分别应用N-硝基主旋精氨酸（L-NNA）和生理盐水静注治疗，分别测量治疗前后血压、血浆NO、环磷酸鸟苷（cGMP）和心钠素（ANF）。结果发现，内毒素休克时，血压下降，血浆NO、cGMP浓度升高，静注L-NNA（20mg／kg）治疗后休克大白兔血压升高，血浆NO、CGMP浓度下降。说明内毒素休克时机体内NO和cGMP产生增加，并与低血压有关，其机理是NO通过激活可溶性鸟苷酸环化酶，使cGMP增高所致，并提示L-NNA具有治疗内毒素休克的价值。     

Nitric oxide synthase inhibition by L-NAME in leukocytopenic patients with severe septic shock

Objectives: To investigate the effects of nitric oxide synthase inhibition by N^G-nitro-l-arginine methyl ester (l-NAME) on hemodynamics and outcome in leukocytopenic ( < 1000/μl) patients with severe septic shock requiring strong vasopressor support. Design: Prospective clinical study. Setting: Medical intensive care unit. Patients: 10 patients with hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement. Intervention: Continuous intravenous infusion of l-NAME (0.3 mg / kg per hour) for a study period of 24 h with prolongation for up to 96 h according to individual requirements. Measurements and results: Compared to baseline values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work index (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of l-NAME treatment. Cardiac output data were unchanged during the study period (p = 0.49). l-NAME was tapered off in five patients who again became responsive to vasopressor medication. Two patients survived the episode of septic shock and vasoactive medication was stopped. Conclusions: The data demonstrate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as indicated by an increase in systemic vascular resistance, mean arterial pressure, and left ventricular stroke work index. Received: 6 June 1996 Accepted: 23 January 1997     

An extreme form of the hyperdynamic syndrome in septic shock

We classified 41 patients in septic shock on the basis of cardiac index (CI) after volume expansion with plasma protein solution, in order to obtain adequate filling pressures. Five had decreased CI (<3.5 l/min per m²), 31 had moderately increased CI (3.5–7.0 l/min per m²) and 5 had extreme hyperdynamic shock with CI superior to 7.0 l/min per m². Among the patients with increased CI, those with extreme hyperdynamic state (EHS) had lower total systemic and pulmonary arteriolar resistances (370 vs 658 and 52 vs 119 dynes·s·cm^-5, respectively) and a higher stroke index (67 vs 46 ml/m²), in spite of similar right atrial pressures. In this latter group, blood lactate was higher (6.5 vs 2.1 mmol/l), acidosis was more severe and coagulation disorders more pronounced; all five patients maintained an extremely high CI until death, which supervened after a brief episode of sinus bradycardia. A similar clinical course was rarely observed in the remaining moderately hyperdynamic group, in which mortality rate was significantly lower (35%). Three of five patients with EHS (compared to 2 of 31 in the moderately hyperdynamic group) had liver cirrhosis, the fourth died of fulminant meningococcemia and the fifth had prolonged polymicrobial bacteremia before adequate treatment was begun. Thus, underlying liver disease or particularly severe and uncontrolled infection seems to predispose to EHS. It is concluded that septic shock with extremely high cardiac output and excessively low peripheral resistances represents a distinct subset with more severe metabolic and coagulation disorders, an unusual hemodynamic evolution and a particularly poor prognosis.     

High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock

Objectives To evaluate the effect of short-term (12-h) high-volume hemofiltration (HVHF) in reversing progressive refractory hypotension and hypoperfusion in patients with severe hyperdynamic septic shock. To evaluate feasibility and tolerance and to compare observed vs. expected hospital mortality.Design and setting Prospective, interventional, nonrandomized study in the surgical-medical intensive care unit of an academic tertiary center.Patients Twenty patients with severe septic shock, previously unresponsive to a multi-intervention approach within a goal-directed, norepinephrine-based algorithm, with increasing norepinephrine (NE) requirements (> 0.3 μg kg^–1 min^–1) and lactic acidosis.Interventions Single session of 12-h HVHF.Measurements and results We measured changes in NE requirements and perfusion parameters every 4 h during HVHF and 6 h thereafter. Eleven patients showed decreased NE requirements and lactate levels (responders). Nine patients did not fulfill these criteria (nonresponders). The NE dose, lactate levels, and heart rates decreased and arterial pH increased significantly in responders. Hospital mortality (40%) was significantly lower than predicted (60%): 67% (6/9) in nonresponders vs. 18% (2/11) in responders. Of 12 survivors 7 required only a single 12-h HVHF session. On logistic regression analysis the only statistically significant predictor of survival was theresponse to HVHF (odds ratio 9).Conclusions A single session of HVHF as salvage therapy in the setting of a goal-directed hemodynamic management algorithm may be beneficial in severe refractory hyperdynamic septic-shock patients. This approach may improve hemodynamics and perfusion parameters, acid-base status, and ultimately hospital survival. Moreover, it is feasible, and safe.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

关于败血症休克发病机理假说的实验（1）

目的 将ＣＡ均有明显增高而临床症状截然相反的败血症休克（ＳＳ）与神经源性肺水肿（ＮＰＥ）进行部分病理生理比较研究，以期从两者差别及ＳＳ的特殊性中，揭示其发病机理。方法 肺系数、ＣＡＰ、ＣＡＷＰ、微循环观察、血浆ＥＴ－１、ＮＯ测定；ＳＳ时ｉＮＯＳ ｍＲＮＡ肺组织原位杂交、Ｎｏｒｔｈｅｒｎ ｂｏｌｔ原位ＰＣＲ、胞内Ｃａ＾＋＋、胞内ＩＰ１、ＩＰ２、ＩＰ３测定。结果 部分生理学指标显示：交感、ＣＡ占优势的     

黄芪联合谷氨酰胺对脓毒症休克患者血浆一氧化氮二胺氧化酶的影响及意义

目的 探讨黄芪与谷氨酰胺联用在脓毒症休克所致肠黏膜缺血/再灌注损伤时的保护作用.方法 选择2005-12～2008-10期间重症监护病房(ICU)符合诊断标准的脓毒症休克患者69例,全部患者按2004年脓毒症诊治指南的规范集束治疗,包括早期目标液体复苏、抗生素治疗、呼吸机治疗、激素治疗、血糖控制等.采用随机对照方法分为三组,各组均实施低热量肠外营养(TPN)治疗,A组为低热量常规TPN对照组,B组为加用谷氨酰胺组,C组为黄芪联合谷氨酰胺组,分别于治疗前及治疗后第1、3、5、7天测定血浆一氧化氮(NO)水平、二胺氧化酶(DAO)活性,并记录急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ),终末观察指标为多器官功能障碍综合征(MODS)发生率、ICU住院时间、28 d病死率.结果 三组治疗前各指标比较差异均无统计学意义(P＞0.05).与A组比较,C组治疗后NO水平进一步下降,第1、3、5天下降明显(P＜0.01);与B组比较,C组NO水平亦下降(P＜0.05),第7天比B组稍偏高,但两组比较差异无统计学意义(P＞0.05).与A组比较,C组治疗后DAO活性逐渐下降,第3、5、7天下降明显(P＜0.01);C组DAO活性与B组比较差异亦有统计学意义(P＜0.05).与A组、B组比较,C组治疗后APACHEⅡ评分、MODS发生率、28 d病死率均下降(P＜0.05).与A组比较,B组、C组ICU住院时间稍有缩短,但差异无统计学意义(P＞0.05).结论 黄芪联合谷氨酰胺加强免疫营养治疗可保护脓毒症休克所致的肠黏膜损伤,并改善患者预后,这与抑制NO的大量产生有关.     

Methylene blue increases systemic vascular resistance in human septic shock

We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation an hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg·kg^–1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.     

Disturbances of selected plasma proteins in hyperdynamic septic shock

This study was performed on patients (n=18) suffering from strictly defined hyperdynamic septic shock. Plasma factors (C-reactive protein, acid ₁-glycoprotien, fibrinogen, fibrinopeptide A, fibrinogen-fibrin split products, factor XIII, antithrobin III, complement factors C3 and C4, inter--trypsin-inhibitor and ₂-macroglobulin) measured during hyperdynamic septic shock were highly abnormal. The activation and consumption of clotting, fibrinolytic and complement factors due to system-specific proteinases (such as thrombokinase or plasminogen activators) seemed to be intensified by the nonspecific proteolytic activity of granulocytic proteinases probably released by the action of endotoxins. Possible therapeutic measures to maintain the endogeneous defence mechanism against enhanced proteolysis during septic shock are discussed.     

高原肺水肿患者血清一氧化氮、一氧化氮合酶及内皮素浓度的变化

目的　观察高原肺水肿患者血清中一氧化氮、一氧化氮合酶及内皮素浓度的变化 ,探讨一氧化氮、一氧化氮合酶、内皮素浓度对高原肺水肿发生、发展的影响。方法　对 34例急进高原的高原肺水肿患者进行治疗前、治愈后血清中一氧化氮、一氧化氮合酶及内皮素含量测定 ,并与 2 0例高原正常健康人作对照研究。结果　高原肺水肿患者血清中一氧化氮、一氧化氮合酶含量在治疗前显著低于治愈后和对照组 (P <0 0 1) ,内皮素含量治疗前显著高于治愈后和对照组 (P <0 0 1) ,治愈后血清中一氧化氮、一氧化氮合酶及内皮素水平与对照组无明显差异 (P >0 0 5 )。结论　高原肺水肿血清中NO、NOS水平降低 ,ET 1水平增高是造成高原肺水肿的重要原因之一 ,其浓度的变化对高原肺水肿的发生、发展及转归产生一定的影响     

氨基胍对创伤性休克大鼠血浆一氧化氮及内皮素变化的影响

目的　探讨一氧化氮合酶抑制剂氨基胍对创伤性休克过程中血浆一氧化氮、内皮素及组织氧分压的影响。方法　采用股骨创伤法建立创伤性休克大鼠模型 ,随机分为对照组与处理组。观察两组大鼠创伤前后及复苏后 1、 3、 5、 12h血浆一氧化氮、内皮素及骨骼肌、肝脏、小肠的组织氧分压的动态变化 ,监测血液动力学变化并记录存活时间。结果　两组大鼠休克末及复苏后各时间点血浆一氧化氮、内皮素浓度及组织氧分压较伤前差异有显著性意义 (P <0 0 5 ) ;同对照组相比 ,处理组休克后期一氧化氮及内皮素浓度明显降低 ,差异有显著性意义 (P <0 0 5 ) ,而休克后期肝脏、小肠氧分压明显高于对照组 ,差异有显著性意义 (P <0 0 5 ) ,处理组复苏后血压明显高于对照组 ,其 12、 2 4存活率也明显高于对照组 ,差异有显著性意义 (P <0 0 5 )。结论　氨基胍可降低血浆一氧化氮、内皮素浓度 ,提高血压 ,改善内脏器官的组织氧分压 ,从而改善创伤性休克大鼠的预后