难治性感染性休克左心室-动脉偶联变化的临床观察

目的探讨难治性感染性休克患者左心室-动脉偶联的变化及其临床意义。方法选择53例难治性感染性休克患者,监测起始点及24 h点心指数(CI)、每搏指数(SVI)、左心室收缩末弹性指数(Eesl)、有效动脉弹性指数(Eal)、有效动脉弹性/左心室收缩末弹性(Ea/Ees)、动脉血乳酸(Lac)和乳酸清除率(r Lac)等指标,将患者分为ΔEa/Ees0组(n=19),ΔEa/Ees≤0组(n=34),随访28 d的患者生存情况。结果随访28 d死亡率发现,ΔEa/Ees0组病死率为68.4%(13/19),显著高于ΔEa/Ees≤0组38.2%(13/34)(χ2=4.444,P=0.035)。ΔEa/Ees0组r Lac为(-2.6±0.3)%,ΔEa/Ees≤0组的r Lac为(5.9±1.3)%,两者存在显著差异(t=9.762,P0.001)。ΔEa/Ees≤0组24 h CI、SVI显著高于ΔEa/Ees0组,Ea I、Ea/Ees显著低于ΔEa/Ees0组,其余项无统计学差异。逐步Logistic回归发现,24 h点ΔEa/Ees、24 h点的APACHE II评分是影响患者28 d死亡的危险因素。结论关注难治性感染性休克中左心室-动脉偶联意义重大,可改善患者组织灌注,从而对改善预后具有重要意义。     

Role of thromboxane,prostaglandins and leukotrienes in endotoxic and septic shock

Intravenous bolus endotoxin elicits a marked but transient increase in plasma TxB₂ and 6-keto-PGF₁ in a large number of species. A smaller, delayed and more prolonged increase in TxB₂ and 6-keto-PGF₁ are reported in animals with septic shock, i.e., those with fecal peritonitis or cecal ligation. Thromboxane synthetase inhibitors or antagonists attenuate endotoxin-induced acute cardiopulmonary changes, the delayed increase in serum lysosomal enzymes, fibrin/fibrinogen degradation products and the thrombocytopenia in a number of species. While these drugs increase survival of rats or mice following endotoxin they do not alter survival of rats in septic shock. These results support the hypothesis that TxA₂ exerts a pathophysiologic effect in shock following bolus endotoxin. In contrast, nonsteroidal antiinflammatory drugs (NSAID) and dietary essential fatty acid deficiency increase survival of rats subjected to endotoxin shock, and survival time in models of septic shock. These results also suggest that some other cyclooxygenase product(s) is involved in septic shock due to fecal peritonitis or cecal ligation. Preliminary experimental studies indicate salutary effects of leukotriene inhibitors and antagonists in endotoxin shock and in models of acute pulmonary injury. Clinical studies have demonstrated elevated plasma TxB₂ and 6-keo-PGF₁ concentrations in patients with septic shock, and elevated LTD₄ in pulmonary edema fluid of patients with the adult respiratory distress syndrome. In view of these clinical and experimental results, clinical trials of NSAID and/or leukotriene inhibitors/antagonists should be considered.     

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.     

Beneficial effects of a 5-lipoxygenase inhibitor in endotoxic shock in the rat

The effects of a highly selective 5-lipoxygenase inhibitor, CGS8515 [methyl 2-[(3,4-dihydro-3,4-dioxo-1-naphthalenyl) amino]benzoate], on endotoxic shock sequelae and eicosanoid synthesis by peritoneal macrophages were evaluated in the rat. Pretreatment of peritoneal macrophages in vitro with CGS8515 significantly inhibited the synthesis (P less than .01) of immunoreactive leukotriene C4/leukotriene D4 stimulated by the calcium ionophore (A23187). Inhibition of 5-lipoxygenase produced significant shunting to immunoreactive thromboxane B2 formation (P less than .05). In rats sedated with ketamine.HCl (82.5 mg/kg) and xylazine. HCl (27.5 mg/kg), i.v. injection of Salmonella enteritidis endotoxin (25 mg/kg i.v.) produced significant decreases at 30 min in mean arterial pressure (from 89 +/- 4 to 44 +/- 8 mm Hg, N = 5, P less than .001); in white blood cell count (from 10.8 +/- 0.6 to 6.5 +/- 0.8 x 10(3)/mm3, N = 5, P less than .01); in platelet count (from 687 +/- 66 to 392 +/- 65 x 10(3)/mm3, N = 5, P less than .01); and produced an increase of hematocrit (from 46 +/- 1.2 to 57.4 +/- 1.8%, N = 5, P less than .03). CGS8515 (5 mg/kg i.v. 30 min before endotoxin injection, N = 6) blunted the endotoxin-induced hypotension by 35% (P less than .001), the leukopenia by 24% (P less than .03), the thrombocytopenia by 45% (P less than .006) and the hemoconcentration by 16% (P less than .03), compared to the shocked control rats 30 min after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of a combination thromboxane receptor antagonist and lipoxygenase inhibitor in traumatic shock

The effects of a thromboxane receptor antagonist having lipoxygenase inhibitory activity, L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropa noic acid) (1 mg/kg per h) were studied in a standardized model of traumatic shock. Pentobarbital (35 mg/kg) anesthetized rats subjected to Noble-Collip drum trauma were characterized by a 82 +/- 12 min survival time, a 20-fold increase in plasma cathepsin D activity, and a 6-fold increase in plasma myocardial depressant factor (MDF) activity. L-655,240 significantly attenuated the accumulation of MDF activity in the plasma (74 +/- 3 vs. 46 +/- 4 units/ml), vehicle vs. drug, respectively, and significantly (P less than 0.01) prolonged survival time to 206 +/- 26 min. However, plasma cathepsin D was not significantly altered with L-655,240 administration during traumatic shock. L-655,240 at 20 micrograms/ml markedly attenuated minced rat lung fragments from producing LTC4 and LTD4.L-655,240 exhibited significant anti-proteolytic activity in pancreatic homogenates. Therefore, L-655,2340 does not stabilize lysosomal membranes directly, but exerts an anti-proteolytic action which appears to curtail the production of a myocardial depressant factor by the ischemic pancreas, thus protecting during traumatic shock. A combination anti-eicosanoid drug such as L-655,240 may therefore prove to be an important therapeutic agent in acute ischemic disorders including traumatic shock.     

Potentiation of the protective effects of a converting enzyme inhibitor and a thromboxane synthetase inhibitor in hemorrhagic shock

The effect of a specific inhibitor of thromboxane (Tx) A2 synthesis, CGS-13080, a new angiotensin converting enzyme inhibitor, CGS-16617, and a combination of both drugs was studied in hemorrhagic shock in rats. Treatment with CGS-16617 (1 microgram/kg) or CGS-13080 (200 micrograms/kg) alone did not alter significantly postoligemic hypotension or the increase in plasma cathepsin D activity in shocked rats, compared with hemorrhaged rats receiving only their vehicle. Combined treatment with both drugs maintained postreinfusion mean arterial blood pressure and attenuated the increase in plasma cathepsin D activity in hemorrhaged rats. Treatment of shocked rats with each drug alone attenuated the accumulation of a myocardial depressant factor activity in the plasma, but the lowest myocardial depressant factor activities were observed in rats treated with the drug combination. Additionally, animals treated with the drug combination exhibited significantly longer postreinfusion survival times than rats receiving either the vehicle (P less than .01), CGS-16617 (P less than .05) or CGS-13080 (P less than .02). CGS-16617 (1 microgram/kg) attenuated significantly the pressor response to angiotensin I throughout the shock period. CGS-13080 attenuated the increase in TxB2 plasma concentrations in shock when compared with hemorrhaged rats receiving the vehicle (P less than .05). Greater attenuation of TxB2 was found after treatment with the drug combination (P less than .01 from vehicle, P less than .05 from CGS-13080 alone). CGS-16617, but not CGS-13080, was also found to have a direct antiproteolytic action in pancreatic homogenates. However, the drug combination (CGS-16617 and CGS-13080) decreased proteolytic activity even further (P less than .001) from CGS-16617 alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

超声评价2型糖尿病患者心脏-血管耦联关系

目的 探讨超声评价2型糖尿病患者心脏-血管耦联关系的临床价值.方法 2型糖尿病患者63例,根据左心室射血分数分为左心室收缩功能正常组(A组)45例与心功能衰竭组(B组)18例,同期健康体检者30例为对照组.测量3组左侧肱动脉压,获取左心室结构、功能及血流动力学参数,计算左心室壁相对厚度、心肌耗氧参数心率血压二重乘积及有效动脉弹性.采用多元线性逐步回归,筛选耦联参数有效动脉弹性的独立关联指标.结果 A,B组心率血压二重乘积较对照组增高(P＜0.01);A,B组左心室收缩末压、心率血压二重乘积比较差异有统计学意义(P＜0.01);3组左心室壁相对厚度、左心室质量指数、左心室射血分数、有效动脉弹性、高密度脂蛋白胆固醇及血糖比较差异均有统计学意义(P＜0.01);进入方程的变量有左心室射血分数、血糖、左心室壁相对厚度、高密度脂蛋白胆固醇和心率血压二重乘积,其标准回归系数的绝对值依次减低,分别为0.471,-0.333,0.236,-0.166和0.133.结论 2型糖尿病患者心脏-血管存在耦联关系,并与生化指标及心肌耗氧参数密切相关.     

尿毒症患者心室-动脉耦联的超声定量评估

目的 探讨超声射频信号血管内中膜分析(QIMT)、动脉硬度分析(QAS)、应变及应变率成像分析(XStrain)技术在评价尿毒症患者心室-动脉耦联(VAC)中的应用价值.方法 尿毒症患者65例,正常受试者30例,均接受心脏及颈动脉超声检查,获得左室射血分数(LVEF)、Tei指数、E/e、僵硬度(β)、顺应性系数(CC)、脉搏波传导速度(PWV)、内中膜厚度(IMT)、应变等指标.以左心室收缩期最大径向应变与颈动脉舒张期最大径向应变之和作为评价VAC的应变指标(VACs),与传统的容积指标(VACv)进行相关分析.将各项指标进行组间比较,以反映尿毒症患者心血管功能及VAC的改变.采用多元线性回归以及ROC曲线分析预测尿毒症患者心功能不全的独立预测因子,评估各因子的贡献,并探讨其理想界值.应用组内相关系数检验XStrain的重复可靠性.结果 ①尿毒症组脉压差、E/e、Tei指数、β、PWV以及IMT均显著高于对照组(P＜0.05).②尿毒症组VAC功能下降,其VACv及VACs均显著低于对照组(P ＜0.05).③VACs作为一项评价VAC的新指标与传统的VACv具有高度的相关性(r=0.908,P=0.000),其测量方法XStrain具有较高的重复可靠性.④VACs、β、VACv和PWV是预测尿毒症患者心功能状态的独立预测因子,其中VACs对心功能状态的影响最大(标准化回归系数为-0.582).以VACs＜23.60作为判断尿毒症患者心功能不全的诊断标准,其灵敏性和特异性均较高(96.4％和81.1％).结论 QIMT、QAS以及XStrain等技术可用来全面综合评估尿毒症患者心血管结构、功能以及VAC的异常情况,为早期发现尿毒症心血管并发症、改善患者预后提供有效的方法.     

Effect of fluid resuscitation on ryanodine receptor in macaques with endotoxic shock

OBJECTIVE: Our recent study demonstrated that sodium bicarbonate improved cardiac function in macaque models with early-phase endotoxic shock. In the present study, we investigated further the ryanodine receptor/calcium release-channel (RyR) and calcium pump after fluid resuscitation of macaques with early-phase endotoxic shock. METHODS: Twenty-four anaesthetised macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mgkg(-1) lipopolysaccharide (LPS). Sixty minutes after the LPS challenge, the animals were given (i) 5 mLkg(-1) normal saline (Ns group, n = 6), (ii) 5 mLkg(-1) of 5% sodium bicarbonate (Sb group, n = 6) or (iii) 5 mLkg(-1) of 3.5% hypertonic sodium chloride (Hs group, n = 7). The control group (Co group, n = 5) received 1 mLkg(-1) normal saline and then with 5 mLkg(-1) normal saline 60 min later. RESULTS: Endotoxin produced a reduction of the density of RyR but did not alter the affinity of RyR. Compared with normal saline, sodium bicarbonate or hypertonic saline induced a restoration of density of RyR but did not influence the affinity of RyR and the calcium pump. CONCLUSION: Up-regulation of RyR performance in myocardium following administration of sodium bicarbonate contributes to the improvement of cardiac function in macaques in the early phase of endotoxic shock.     

Effects of a novel guanylyl cyclase inhibitor on the vascular actions of nitric oxide and peroxynitrite in immunostimulated smooth muscle cells and in endotoxic shock.

OBJECTIVE: Nitric oxide (NO), produced by the inducible isoform of NO synthase (NOS) in circulatory shock exerts cytotoxic and vasodilator effects. Part of these effects are mediated by formation of peroxynitrite, a toxic oxidant produced by the rapid reaction of NO and superoxide. Other parts of the vascular actions of NO in shock are thought to be mediated by the action of NO on the soluble guanylyl cyclase (GC) in the smooth muscle and subsequent decrease in the intracellular calcium levels. Using 1H-(1,2,4)oxadiazolo(4,3-alpha)quinoxalin-1 -one (ODQ), a potent inhibitor of GC, we studied the role of GC activation in the NO- and peroxynitrite-related vascular alterations. DESIGN: In vitro: Controlled experiment using cultured rat aortic smooth muscle cells. In vivo: Prospective, randomized, controlled animal study. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats and male Swiss mice. Interventions: In vitro: a) Stimulation of rat aortic smooth muscle cells with bacterial lipopolysaccharide (LPS) and gamma-interferon, measurement of the production of nitrite and nitrate (breakdown products of NO), and suppression of mitochondrial respiration for 24 to 48 hrs, in the presence or absence of ODQ; and b) in norepinephrine-precontracted endothelium-denuded thoracic aortic rings, exposure to LPS (10 ng/mL) in the presence or absence of ODQ. In vivo: Rats treated in vivo with LPS (10 mg/kg iv for 3 hrs) and mice challenged with 60 mg/kg LPS ip, in the presence or absence of ODQ. MEASUREMENTS AND MAIN RESULTS: Stimulation of rat aortic smooth muscle cells with bacterial LPS and gamma-interferon induced the production of nitrite and nitrate (breakdown products of NO) and suppression of mitochondrial respiration for 24 to 48 hrs. The amount of NO produced was slightly enhanced with ODQ (10-100 EM), whereas the suppression of mitochondrial respiration was not affected by ODQ (1-100 microM). ODQ did not affect the degree of suppression of mitochondrial respiration in response to NO donor agents or to peroxynitrite. Exposure to LPS (10 ng/mL) for 6 hrs caused a time-dependent relaxation of norepinephrine-precontracted endothelium-denuded thoracic aortic rings. This response was caused by the expression of inducible NOS and could be blocked by pharmacologic inhibitors of NOS such as N(G)-methylL-arginine. ODQ (1 microM) prevented the LPS-induced loss of vascular tone in this experimental system. Similar to the in vitro responses, there was a significant suppression of the norepinephrine-induced contractions in ex vivo experiments, in which rings were taken from animals treated in vivo with LPS (10 mg/kg for 3 hrs). ODQ treatment in vitro (1 microM) caused a complete restoration of the contractile responses. In mice challenged with 60 mg/kg LPS ip, ODQ (20 mg/kg), given either as a pretreatment or as a 4-hr posttreatment, improved survival at 24-144 hrs. CONCLUSION: These studies indicate that GC activation does not contribute to NO- or peroxynitrite-induced cytotoxicity but does contribute to the vascular hyporeactivity induced by endotoxin in vitro and in vivo. GC inhibition alone is sufficient to influence survival in a murine model of severe sepsis.     

Effect of selective thromboxane synthetase inhibitor on vein grafts

We evaluated the effect of a selective thromboxane synthetase inhibitor (TSI) on the patency of autogenous vein grafts in dogs. Treatment involved oral dosing (10 mg/kg bid) of TSI or placebo, combined with local treatment of the graft with TSI or placebo (papavarine) at the time of implantation. At harvest, two animals, one from each oral dosing group, had an occluded graft; both grafts had been locally treated with papavarine. We found no significant histopathologic difference between graft treatment groups. Attempts to estimate the effect of TSI dosing on the prostacyclin/thromboxane balance through radioimmunoassay analysis of graft perfusates were unsuccessful. As measured by in vitro platelet aggregation, oral TSI was found to alter platelet function, though not in a dose-dependent fashion, and the animals rebounded toward normal at 12 hours.     

Effects of the angiotensin-converting enzyme inhibitor perindopril on endothelial injury and hemostasis in rabbit endotoxic shock

Objective To assess the effects of the angiotensin-converting enzyme (ACE) inhibitor (ACEI) perindopril on prolonged endothelial cell dysfunction in a rabbit endotoxic model.Design Randomized, controlled, interventional trial.Setting University animal laboratory.Subjects A total of 65 male New Zealand White rabbits, randomly assigned to one of eight groups.Interventions Endotoxic shock was induced by a single lipopolysaccharide (LPS, serotype O55:B5) bolus (0.5 mg.kg^–1, i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor (TF) were determined by functional assay. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess endothelial injury of the abdominal aorta. These parameters were studied 5 days (D5) after the onset of endotoxic shock. Rabbits were randomized to receive perindopril (1 mg kg^–1 day^–1 orally) alone, or with N^G-nitro-L-arginine methyl ester (L-NAME; 15 mg kg^–1 day^–1 orally), or L-NAME alone initiated 7 days before the onset of endotoxic shock and maintained for 5 days afterward.Measurements and results Perindopril prevented altered endothelium-dependent relaxation to acetylcholine induced by LPS injection (E_max=75.6±3.7 vs 42.3±9.4% in LPS group, p<0.05). This effect was inhibited by co-treatment with L-NAME. Perindopril had no effect on either LPS-induced endothelial histological injury or monocyte TF expression.Conclusion These data suggest that perindopril can prevent endothelial dysfunction in endotoxin-induced shock through an NO-dependent mechanism.     

应用超声初步探讨高血压患者心-血管耦联

目的 应用超声评价高血压患者心脏、血管弹性变化及二者弹性匹配关系,初步探讨心-血管耦联.方法 原发性高血压患者50例,年龄和性别相匹配的30例受试者作为对照组.采用超声心动图法获取左室结构、功能和血流动力学参数,测量平静状态下肱动脉血压和颈-股脉搏波传播速度.计算心脏、大动脉弹性及两者耦联的相应参数:心室收缩末压(ESP)、有效动脉弹性(Ea)、心室舒张末弹性(Ed)、左室收缩末弹性(Ees)和Ea/Ees.结果 Ees与左室射血分数(r=0.378,P=0.005)、Ea与颈-股脉搏波传播速度(r=0.289,P＜0.001)均呈正相关,Ed与e/a(r=- 0.333,P=0.027)呈负相关,左室后壁厚度与Ed和Ea呈正相关(r=0.388,P=0.016和r=0.336,P=0.026).高血压组的Ea和Ed较对照组明显增高(P＜0.05),Ees和Ea/Ees两组差异无统计学意义(P＞0.05).结论 高血压患者动脉与心脏弹性变化相互关联,两者的匹配可评价心-血管耦联.     

Differential effects of a selective inhibitor of soluble guanylyl cyclase on global and regional hemodynamics during canine endotoxic shock

Activation of soluble guanylyl cyclase (sGC) might occur early during septic shock and play a role in the regulation of vascular tone and the redistribution of blood flow. The aim of this study was to assess the effects of sGC inhibition with oxadiazoloquinoxalinone (ODQ) on global and regional hemodynamic parameters in a clinically relevant model of septic shock. Fifteen anesthetized adult mongrel dogs were equipped with femoral and pulmonary artery catheters and ultrasonic flow probes around the mesenteric, femoral and renal arteries. The animals were randomized to receive Escherichia coli endotoxin (2 mg/kg, i.v.) alone, endotoxin followed by ODQ (1 mg/kg i.v.), or ODQ alone. Endotoxin administration was followed by decreases in mean arterial pressure, cardiac index, mesenteric, renal and femoral blood flows (MBF, RBF and FBF), and increases in systemic and pulmonary vascular resistances. Fluid resuscitation restored cardiac index, systemic vascular resistance, pulmonary vascular resistance, MBF, RBF and FBF to pre-endotoxin levels. In the presence of endotoxin, ODQ administration increased MBF and prevented the restoration of FBF. Hence, selective inhibition of sGC may increase splanchnic blood flow in septic shock.     

A selective inhibitor for inducible nitric oxide synthase improves hypotension and lactic acidosis in canine endotoxic shock.

OBJECTIVE: To investigate whether ONO-1714, a putative selective inhibitor for inducible nitric oxide synthase, modulates systemic hemodynamics, arterial blood gases, lactate concentrations, gastric mucosal perfusion, and renal and hepatic functions in endotoxic shock. DESIGN: Prospective, randomized, controlled animal study. SETTING: Laboratory at a university hospital. SUBJECTS: Eighteen male beagle dogs (12-19 kg) under pentobarbital anesthesia. INTERVENTIONS: Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. They were divided in three groups: a) lipopolysaccharide (LPS) plus vehicle group (n = 6), which received LPS (250 ng/kg/min for 2 hrs) and saline 1 hr later; b) LPS plus ONO (0.05) group (n = 6), which received ONO-1714 (0.05 mg/kg) 1 hr after the start of LPS; c) LPS plus ONO (0.1) group (n = 6), which received ONO-1714 (0.1 mg/kg) 1 hr after the start of LPS. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, blood gas parameters, gastric intramural pH, urine output, and serum levels of lactate, transaminases, bilirubin, and creatinine were measured during a 6-hr observation period. LPS induced hypotension, lactic acidosis, gastric mucosal acidosis, and renal and hepatic dysfunction. ONO-1714 reversed the LPS-induced hypotension and lactic acidosis without deteriorating cardiac output, oxygen delivery, or gastric mucosal acidosis. CONCLUSIONS: These findings suggest that ONO-1714 is a useful agent to reverse hypotension and lactic acidosis in a canine endotoxic shock model.     

Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock

OBJECTIVE: To test the hypothesis that nonselective adsorption by a hydrophobic resin of cytokines and other proinflammatory mediators could improve 72-hr survival in a rabbit model of endotoxic shock. DESIGN: Prospective, randomized, controlled animal trial. SETTING: Animal care facility at a research institution. SUBJECTS: A total of 109 New Zealand white male rabbits. INTERVENTIONS: Anesthetized rabbits were cannulated with indwelling femoral arterial and venous lines. Septic shock was induced by a single intravenous injection of Escherichia coli lipopolysaccharide. The dose was experimentally assessed in 40 rabbits receiving 1.0, 0.5, 0.1, and 0.05 mg/kg body weight to determine LD80 at 72 hrs. Extracorporeal circulation consisted of plasma filtration coupled with passage of the plasma filtrate through a hydrophobic sorbent and reinfusion into the venous line. The extracorporeal treatment lasted for 3 hrs. Rabbits injected with endotoxin (0.05 mg/kg) were submitted to plasma filtration with (19 rabbits) or without (20 rabbits) sorbent adsorption. As controls, rabbits injected with vehicle alone were treated with plasma filtration (ten rabbits) or without (ten rabbits) sorbent adsorption. Ten rabbits were monitored under anesthesia to determine basal survival. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of endotoxin, bioactive tumor necrosis factor, resin-adsorbed platelet-activating factor, mean arterial pressure, base excess, and white cell count were assessed and a global severity score was established. At 72 hrs, cumulative survival was significantly (p = .0041) improved in septic rabbits treated with coupled plasma filtration-adsorption. Circulating tumor necrosis factor bioactivity remained similar in control and treated rabbits. Biologically significant amounts of platelet activating factor were eluted from the sorbent during the entire treatment time. The severity score inversely correlated with survival (p < .001). CONCLUSIONS: Coupled plasma filtration-adsorption improved survival in a rabbit model of endotoxic shock. Coupled plasma filtration-adsorption may be an extracorporeal treatment capable of removing structurally different inflammatory mediators associated with sepsis.     

Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model

Introduction  

The inducible nitric oxide synthase (iNOS) plays a crucial role in early sepsis-related microcirculatory dysfunction. Compared to a catecholamine therapy we tested effects of a specific iNOS-inhibitor (1400W) on the microcirculatory function in the brain.     

大黄抗内毒素性休克大鼠炎性介质作用的实验研究

目的：研究大黄对内毒素性休克大鼠炎性介质作用的机制。方法：选用大鼠内毒素性休克模型。随机分为６组：单纯手术组、内毒素组、大黄预防用药组（１５０ｍｇ／ｋｇ组和７５０ｍｇ／ｋｇ组）和大黄治疗组（１５０ｍｇ／ｋｇ组和７５０ｍｇ／ｋｇ组）。检测磷脂酶Ａ２（ＰＬＡ２）和血小板活化因子（ＰＡＦ）的活性。结果：内毒素注射前６组大鼠平均动脉压（ＭＡＰ）无显著性差异；注射内毒素后４小时ＭＡＰ明显降低；大黄预防用药组和大黄治疗组ＭＡＰ则与注射内毒素前及单纯手术组比较均无明显变化，并均显著高于内毒素组注射内毒素４小时后。注射内毒素后４小时，血清和小肠组织中ＰＬＡ２活性及ＰＡＦ含量均明显增高；与内毒素组注射内毒素后４小时比较，大黄预防组和治疗组则血清和小肠组织中ＰＬＡ２活性和ＰＡＦ含量显著降低。结论：大黄对内毒素性休克所致炎症反应有明显的预防和治疗作用     

迷走神经兴奋对内毒素休克兔生命体征的影响

目的 探讨电刺激迷走神经对内毒素(lipopolysaccharide,LPS)休克兔生命体征变化的影响.方法 16只兔随机分为刺激组(S组)和对照组(C组).两组均切断舣侧颈迷走神经干,按600μg/kg静注大肠杆菌LPS.S组选择左迷走神经近心端接刺激电极,在注射LPS前后各持续电刺激(电压10 V,频率5 Hz,波宽5 ms)10 min.分别于输注LPS前及后30,60,120,180,240和300 min记录心率(HR)和平均动脉压(MABP),检测血清中肿瘤坏死凶子(TNF-α)和白介素10(IL-10)含量.结果 兴奋迷走神经能缓解LPS引起的低血压休克,同时与C组比较,S组血清中TNF-α显著降低[(38.12±7.85)ps/mL vs.(55.12±7.89)ps/mL,P<0.01]而IL-10水平明显升高[(55.12±9.37)pg/mL vs.(40.15±5.44)ps/mL,P<0.01].结论兴奋迷走神经可以改善LPS休克兔的生命体征,这种现象可能与迷走神经影响体内炎症介质的合成有关.