川芎嗪联合高渗盐对心搏骤停大鼠脑复苏作用的实验研究

目的 研究川芎嗪联合高渗盐对心搏骤停大鼠复苏后脑组织的保护作用,探讨脑复苏治疗的有效方法.方法 32只SD大鼠被随机分成4组(每组8只):生理盐水组、川芎嗪组、高渗盐水组、川芎嗪联合高渗盐水组.窒息导致心搏骤停模型复制成功后,实验各组于复苏即刻分别静脉注射生理盐水、川芎嗪、高渗盐水、川芎嗪联合高渗盐水,比较各组大鼠自主循环恢复(ROSC)时间、动脉血及脑匀浆丙二醛(MDA)、脑干湿重比(D/W)、平均动脉压(MAP)、神经功能缺损评分(NDS)及脑海马组织病理改变.结果 与对照组相比,联合用药组、高渗盐组、川芎嗪组大鼠自主循环恢复时间(P＜0.05)明显改善,10 min、30 min和60 min的平均动脉压明显提高,24、48 h较对照组明显改善NDS(P＜0.01),大鼠48 h存活率显著提高,大脑干湿重比值增加(P＜0.05)及脑组织病理损伤减轻;联合用药组较川芎嗪组、高渗盐组上述观测指标有显著改善.与对照组相比,联合用药组及川芎嗪组1 h动脉血MDA明显降低(P＜0.05),48 h脑匀浆MDA降低(P＜0.05),联合用药组较川芎嗪组1小时动脉血、48 h脑匀浆MDA亦明显降低;与对照组相比,高渗盐组1 h动脉血MDA差异无统计学意义(P＞0.05),48 h脑匀浆MDA差异亦无统计学意义(P＞0.05);且高渗盐组较川芎嗪组ROSC时间、ROSC后60 min MAP、24和48 h NDS、大脑干湿重比差异无统计学意义(P＞0.05).结论 静脉注射川芎嗪联合高渗盐能减轻大鼠心跳呼吸骤停复苏后脑组织损伤,改善脑功能;联合应用两药可提高疗效.     

Cerebral hemodynamics after hemorrhagic shock: effects of the type of resuscitation fluid

Cerebral blood flow (CBF), cerebral oxygen delivery, and intracranial pressure were measured in 12 dogs subjected to hemorrhagic shock and then resuscitated with lactated Ringer's solution or 6% hetastarch. Hemorrhagic shock was produced by the rapid removal of blood to achieve a mean arterial pressure (MAP) of 40 mm Hg with BP maintained at that level for 30 min. Six animals were resuscitated with lactated Ringer's solution, 60 ml/kg iv, and six with 6% hetastarch, 20 ml/kg iv. Both solutions effectively restored systemic hemodynamic stability, increasing cardiac output and MAP. Intracranial pressure was significantly (p less than .05) lower after resuscitation in the hetastarch group, but CBF, which had decreased during shock, was not normalized by either fluid, and cerebral oxygen transport fell further with resuscitation secondary to a hemodilutional reduction of hemoglobin. Although 6% hetastarch may improve systemic hemodynamics and maintain a low intracranial pressure during resuscitation, it fails, as does lactated Ringer's solution, to restore cerebral oxygen transport to prehemorrhagic shock levels.     

高渗盐干预心脏骤停后心肺复苏的研究进展及前景

心脏骤停的诊治是急诊医生面临的重要难题。除指南推荐的传统药物,如肾上腺素、血管加压素外,近年研究发现,高渗盐可能有利于心肺复苏的治疗。本文就高渗盐干预心脏骤停的机制、相关动物及临床研究进展进行综述。     

Functional metabolic heart impairment after acute lethal hemorrhage followed by resuscitation.

Effects of acute lethal blood loss on postresuscitation heart impairment has been studied. Experiments were performed in mongrel male rats anesthesized with sodium pentobarbital (25 mg/kg). Functional metabolic heart impairments have been evaluated in different terms after resuscitation by isolated perfused heart method (Fallen et al., J. Appl. Physiol, 22 (1967) 836-839). It has been established that maximal heart injury occurs in the first hours after resuscitation. It is supported by the following findings: depression of myocardium contractile function grew; enzyme excretion from cardiomyocytes in coronary flow increased: efficacy of glucose utilization by means of carried function decreased; pyruvate excretion in coronary flow elevated. Because of severe course of postresuscitation period functional metabolic heart disturbances are more pronounced and preserved for a long time.     

Cerebral vasospasm after subarachnoid hemorrhage: an update

Cerebral vasospasm is a significant problem after subarachnoid hemorrhage, with often devastating consequences. Its pathogenesis remains poorly understood despite extensive research. Owing to the lack of a clear etiology, medical treatment is still largely limited to triple-H therapy and calcium channel blockers, although newer treatments such as percutaneous transluminal angioplasty and papaverine infusion are becoming more common. Clinical symptoms are often first noted by the registered nurse, who must then alert the physician to the need for diagnostic workup and therapy. Caring for patients after subarachnoid hemorrhage requires awareness of the potential for the development of vasospasm, and knowledge of the steps necessary to ensure its timely diagnosis and treatment. This article will review the current body of knowledge as it pertains to vasospasm and outline the direction of ongoing research.     

Glucosamine administration during resuscitation improves organ function after trauma hemorrhage

Stress-induced hyperglycemia is necessary for maximal rates of survival after severe hemorrhage; however, the responsible mechanisms are not clear. One consequence of hyperglycemia is an increase in hexosamine biosynthesis, which leads to increases in levels of O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on nuclear and cytoplasmic proteins. This modification has been shown to lead to improved survival of isolated cells after stress. In view of this, we hypothesized that glucosamine (GlcNH2), which more selectively increases the levels of O-GlcNAc administration after shock, will have salutary effects on organ function after trauma hemorrhage (TH). Fasted male rats that underwent midline laparotomy were bled to a mean arterial blood pressure of 40 mmHg for 90 min and then resuscitated with Ringer lactate (four times the shed blood volume). Administration of 2.5 mL of 150 mmol L GlcNH2 midway during resuscitation improved cardiac output 2-fold compared with controls that received 2.5 mL of 150 mmol L NaCl. GlcNH2 also improved perfusion of various organs systems, including kidney and brain, and attenuated the TH-induced increase in serum levels of IL-6 (902+/-224 vs. 585+/-103 pg mL) and TNF-alpha (540+/-81 vs. 345+/-110 pg mL) (values are mean+/-SD). GlcNH2 administration resulted in significant increase in protein-associated O-GlcNAc in the heart and brain after TH. Thus, GlcNH2 administered during resuscitation improves recovery from TH, as assessed by cardiac function, organ perfusion, and levels of circulating inflammatory cytokines. This protection correlates with enhanced levels of nucleocytoplasmic protein O-GlcNAcylation and suggests that increased O-GlcNAc could be the mechanism that links stress-induced hyperglycemia to improved outcomes.     

Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation

BACKGROUND: Methylene blue (MB) administered with a hypertonic-hyperoncotic solution reduces the myocardial and cerebral damage due to ischaemia and reperfusion injury after experimental cardiac arrest and also increases short-term survival. As MB precipitates in hypertonic sodium chloride, an alternative mixture of methylene blue in hypertonic sodium lactate (MBL) was developed and investigated during and after cardiopulmonary resuscitation (CPR). METHODS: Using an experimental pig model of cardiac arrest (12 min cardiac arrest and 8 min CPR) the cardio-cerebral and metabolic effects of MBL (n=10), MB in normal saline (MBS; n=10) or in hypertonic saline dextran (MBHSD; n=10) were compared. Haemodynamic variables and cerebral cortical blood flow (CCBF) were recorded. Biochemical markers of cerebral oxidative injury (8-iso-PGF2alpha), inflammation (15-keto-dihydro-PGF2alpha), and neuronal damage (protein S-100beta) were measured in blood from the sagittal sinus, whereas markers of myocardial injury, electrolytes, and lactate were measured in arterial plasma. RESULTS: There were no differences between groups in survival, or in biochemical markers of cerebral injury. In contrast, the MBS group exhibited not only increased CKMB (P<0.001) and troponin I in comparison with MBHSD (P=0.019) and MBL (P=0.037), but also greater pulmonary capillary wedge pressure 120 min after return of spontaneous circulation (ROSC). Lactate administration had an alkalinizing effect started 120 min after ROSC. CONCLUSIONS: Methylene blue in hypertonic sodium lactate may be used against reperfusion injury during experimental cardiac arrest, having similar effects as MB with hypertonic saline-dextran, but in addition better myocardial protection than MB with normal saline. The neuroprotective effects did not differ.     

高渗氯化钠溶液复苏失血性休克的研究进展

<正>创伤患者的死亡绝大多数发生在创伤后1h内,即所谓的"黑色时间"内,致死的主要原因是严重创伤后失血性休克。研究表明,通过创伤后早期的正确处理,可明显减少创伤的死亡率,其中失血性休克的复苏是救治的关键环节。自1980年Velasco等[1]首次报道用小剂量高渗氯     

Cardiorespiratory and conjunctival oxygen tension monitoring during crystalloid resuscitation after hemorrhage

Conjunctival oxygen tension (Pcj0₂) monitoring provides a continuous, noninvasive assessment of tissue oxygenation and perfusion. In this study, the relationship between Pcj0₂ and standard cardiorespiratory variables was examined during sequential, stepwise crystalloid resuscitation after acute hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Posthemorrhage values for Pcj0₂ were approximately 5% of prehemorrhage values. Blood pressure rose rapidly during the early stages of resuscitation, and after 40% of the shed blood volume had been replaced with crystalloid was no longer significantly different from prehemorrhage values. Pcj0₂ rose in a linear manner during resuscitation and achieved values that were not significantly different from control when 70% of the shed blood volume had been replaced with crystalloid. When all of the shed blood volume had been replaced with crystalloid, cardiac index, left and right cardiac work index, and oxygen delivery remained significantly less than control levels. These results indicate that PcjO₂ normalizes before crystalloid resuscitation is complete, but after blood pressure and other noninvasively measured parameters return to prehemmorrhage levels.     

Slightly hypertonic saline and dextran-40 in resuscitation of methamphetamine burn patients.

The inherent danger of illegal manufacture of methamphetamine is explosion and fire with the "cookers" presenting to burn centers for treatment. Recent studies have shown that methamphetamine burn patients required resuscitation volumes two to three times that of the standard Parkland formula and experienced a higher mortality rate. The purpose of this study was to compare the fluid resuscitation requirements and other characteristics of our methamphetamine-positive burn patients with a control group of methamphetamine-negative burn patients. A retrospective study of burn patients with methamphetamine-positive urine toxicology screens was conducted from August 1996 to April 2005. The data collected were age, sex, %total body surface area (%TBSA) burn, urine toxicology screen result, length of stay (LOS), ventilator days, weight, urine output, and fluid requirement during the first 24 hours along with fluid type, survival, and hospital charges. Methamphetamine-positive patients were matched to controls for %TBSA, age, and sex. Eleven methamphetamine-positive burn patients were well matched with 11 methamphetamine-negative controls. There was no difference in intubation rate, ventilator days, LOS, and there were no deaths in either group. There was no statistical difference between the two groups for the ratio of the 24-hour fluid resuscitation requirement divided by the estimate from the Parkland formula. Hospital charges were similar for the two groups. The largest volume of fluid infused was lactated Ringers (LR) and the slightly hypertonic fluid combination of LR + 50 mEq sodium bicarbonate + 3.4 mmol potassium phosphate. Both groups also received a dextran-40 (Rheomacrodex) infusion. In contrast to previous studies, our experience with methamphetamine-positive burn patients shows that they did not have an increased initial fluid requirement, a longer LOS, more days on the ventilator, higher hospitalization charges nor an increased mortality rate. The only apparent difference between our study and others is in the method of resuscitation. The slightly hypertonic fluid combination of LR + 50 mEq sodium bicarbonate +3.4 mM potassium phosphate was used for resuscitation along with Rheomacrodex. Prospective trials should be conducted on this fluid resuscitation strategy to determine wider applicability for all large burn patients.     

Cerebral density on CT immediately after a successful resuscitation of cardiopulmonary arrest correlates with outcome

PURPOSE: To evaluate whether cerebral CT findings taken immediately after successful resuscitation from cardiopulmonary arrest (CPA) correlate with the outcome or not. MATERIAL AND METHODS: We analyzed retrospectively brain sections with the Housfield unit (CT number). Between May 2001 and March 2004, 16 consecutive patients, who recovered from CPA, were included as subjects in this study. They satisfied all of the following criteria: (a) a helical multislice head CT was performed within 1 h of the return of the spontaneous circulation (ROSC); (b) patients died within 24 h after ROSC, and any patients with trauma or cerebral vascular disease were excluded. The subjects were divided into two groups; those with a cerebral performance category of 1-3 (GR group) and those with a cerebral performance category of 4-5 (VD group). RESULTS: There were no significant differences between the two groups except for age. The average ventricle size on the brain CT showed no significant difference between the two groups. The average CT number of the putamen and cerebral cortex, and the corticomedullary contrast in the GR group were higher than those in the VD group. CONCLUSION: Although the influence of age cannot be disregarded, the CT number of the putamen and cortex, and also the corticomedullary contrast correlated with outcome of hypoxic encephalopathy even when cerebral CT was performed within 1 h after ROSC following CPA.     

Gut gavage with antiendotoxin antibodies reduces the liberation of tumor necrosis factor-alpha after hemorrhage/resuscitation

OBJECTIVE: To evaluate the effect of gut gavage both alone and with enteral administration of monoclonal antibodies to endotoxin on the liberation of tumor necrosis factor (TNF)-alpha and subsequent hemodynamics after hemorrhage/resuscitation. DESIGN: Dose response intervention, sham-controlled animal study. SETTING: Research laboratory at a university medical center. ANIMALS: Instrumented rats (250-325 g body weight) underwent standardized hemorrhage/resuscitation. INTERVENTIONS: Animal groups received 4 hrs before hemorrhage/resuscitation: gastric gavage with Colyte alone (group 1), combined with E5 antiendotoxin at either 0.2 mg/100 g (group 2) or 2 mg/100 g body weight (group 3), or sham controls (group 4). There were six animals studied in each of the four groups. MEASUREMENTS AND MAIN RESULTS: For animals receiving gut gavage and high-dose E5 antiendotoxin, plasma concentrations of TNF-alpha (pg/mL) at 120 mins after hemorrhage/resuscitation were significantly lower compared with sham controls (16+/-4 group 3; 65+/-36 group 4; mean +/- SD, p < .05). At 300 mins, this same treatment group had a significantly higher mean blood pressure (mm Hg) (110+/-6 group 3; 86+/-7 group 4: p < .05). Also at 300 mins after hemorrhage/resuscitation, plasma lactate concentrations (mmol/L) were significantly lower for all gut gavage treatment groups compared with sham control animals (1.9+/-0.2 group 1; 2.0+/-0.2 group 2; 1.8+/-0.2 group 3; 4.8+/-2.8 group 4, p < .05). CONCLUSIONS: Prior treatment with gut gavage and enterally administered antiendotoxin antibodies reduces TNF-alpha liberation after hemorrhage/resuscitation and confers a subsequent improvement in hemodynamics and decreased plasma lactate concentrations. Such therapy may be efficacious in patients undergoing elective procedures where major hemorrhage is likely or in severely injured patients with continued or recurrent hemorrhage.     

Stages of disseminated intravascular coagulation after resuscitation in patients with massive hemorrhage and severe multiple trauma

Changes in blood coagulation and fibrinolysis were followed up in 255 patients of intensive care wards during 5 days after effective treatment of grave and terminal stages of traumatic hemorrhagic shock. Four stages in the development of disseminated intravascular coagulation (DIC) were distinguished. Special attention is paid to the time course of the third stage with repeated hypercoagulation, suppressed fibrinolysis, and microthrombolysis in organs and tissues leading to multiple organ failure. The fourth stage of DIC is described, when involvement of the organs and generalized inflammation or sepsis is associated with remote (on days 3-5 and later) hemorrhages. These hemorrhages are apparently caused by disorders in fibrin production but not by acute fibrinolysis and consumption coagulopathy, as during the second stage of DIC.     

肝素钠和小剂量高渗盐水对心肺复苏后兔小肠微循环灌注障碍的影响

目的:研究心肺复苏期间肝素钠和小剂量高渗盐水治疗对自主循环恢复后兔小肠微循环灌注的影响.方法:23只家兔开胸交流电致心室颤动,心室颤动5 min后行胸内心肺复苏,心肺复苏过程中随机滴注生理盐水(NS组)2mL/(kg·10 min)或生理盐水2 mL/(kg·10 min)加普通肝素钠60u/kg(H组)或7.5%NaCL 2 mL/(kg·10 min)+普通肝素钠60 u/kg(HSH组),另有3只家免作为假手术组,只进行外科手术操作,不给予致颤和心肺复苏.自主循环恢复后30min注入10%异硫氰酸荧光素钠-白蛋白0.3 mL/kg标记全身血液,循环2 min后处死动物取回肠末段,观察微循环灌注情况.结果:NS组中8只动物,6只完成实验;H组和HSH组各6只,各有5只完成实验.各组动物的生理学参数差异无统计学意义(P>0.05).兔经历5 min心跳骤停和心肺复苏后,在自主循环恢复后仍有严重的微循环灌注障碍,NS组的小肠微循环灌注面积为(22.78±4.21)%;H组为(29.73±1.21)%,和NS组相比二者差异有统计学意义(P<0.01);HSH组为(68.36±7.43)%,和其他2组相比差异均有统计学意义(P<0.05);而3只假手术组的动物显示了均匀一致的微循环灌注.结论:心肺复苏期间给予肝素钠和小剂量高渗盐水治疗可以改善复苏后兔小肠微循环灌注障碍.     

Hematology patterns after hemoglobin-based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

BACKGROUND: The hemoglobin-based oxygen carrier (HBOC-201) resuscitation fluid improves outcome in hemorrhagic shock swine models with minimal coagulopathy. Herein, coagulation parameters were evaluated after resuscitation with HBOC-201 after severe bleeding and prolonged delay to definitive care. STUDY DESIGN AND METHODS: After 55 percent estimated blood volume-controlled hemorrhage by catheter withdrawal, swine (n=48) were resuscitated with HBOC-201 or Hextend (HEX) infused in four doses over 4 hours or not resuscitated (NON). Animals were randomly assigned in two cohorts of 4- or 24-hour simulated delay to hospital arrival (access to blood and saline infusions up to 72 hr). In vitro hematologic monitoring was assessed with complete blood count, hemostasis (thromboelastography [TEG], in vitro bleeding time [PFA]), and coagulation (prothrombin time [PT], thrombin-antithrombin, fibrinogen) indices. RESULTS: Within groups, survival was unaffected by extending delay from 4 to 24 hours. Combined survival was similar for HBOC-201 and HEX but lower for NON animals (93.5, 81.5, and 25 percent, respectively; p<0.01). Blood transfusion requirements were lower with HBOC-201 than HEX. Elevated TEG and PFA parameters in resuscitated animals reflected fluid and blood transfusion regimens. TEG reaction time and PFA were transiently higher with HBOC-201 than with HEX during the early hospital phase. PT was increased in HEX animals. CONCLUSION: In this severe model, survival was equivalent with HBOC-201 and HEX resuscitation. HBOC-201 or HEX allowed delayed hospital arrival to 24 hours without worsening coagulation parameters, but dilutional mild coagulopathy in the hospital phase persisted with HBOC-201 due to blood transfusion avoidance. Low hematocrit suggests that blood administration after HBOC-201 resuscitation could be beneficial to replete blood cellular mass.     

高渗氯化钠溶液复苏抑制失血性休克大鼠肺细胞凋亡的初步研究

目的 探讨高渗氯化钠溶液(HS)复苏对失血性休克大鼠肺细胞凋亡的影响及其意义. 方法 将23只SD大鼠制作成重度失血性休克模型,随机分为假手术组(Sham组,8只)、高渗氯化钠溶液复苏组(HS组,9只)和等渗盐水复苏组(NS组,6只),采用流式细胞仪FITC-AnnexinV/PI荧光染色法定量测定休克/复苏后各组大鼠肺组织细胞的凋亡情况,并加以比较和分析. 结果 在失血性休克/复苏后的早期阶段,HS组和NS组大鼠的肺组织细胞即有大量凋亡发生,其肺细胞凋亡率均明显高于Sham组,差异有统计学意义(P＜0.01).同时,NS组大鼠的肺细胞凋亡率则显著高于HS组,差异有统计学意义(P＜0.01). 结论 在重度失血性休克大鼠模型中,与等渗盐水复苏相比较,高渗氯化钠溶液复苏能显著抑制失血/复苏后肺细胞的凋亡,有助于减轻休克后急性肺损伤,这可能也是高渗氯化钠溶液复苏肺保护作用的重要机制之一.