Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke

We tested the hypothesis in a rat model that body cooling suppresses circulatory shock and cerebral ischemia in heatstroke. Animals under urethane anesthesia were exposed to water blanket temperature (Tblanket) of 42 degrees C until mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the hippocampus began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 26 degrees C. Extracellular concentrations of glutamate, glycerol, lactate, and lactate/pyruvate in the hippocampus were assessed by microdialysis methods. Cooling was accomplished by decreasing Tblanket from 42 degrees C to 16 degrees C. The values of MAP and CBF after the onset of heat stroke in heatstroke rats received no cooling were all significantly lower than those in control rats. However, the neuronal damage score and extracellular levels of ischemia and damage markers in the hippocampus were greater. Cooling immediately after the onset of heatstroke reduced the heatstroke-induced circulatory shock, cerebral ischemia, neuronal damage, and surge of tissue ischemia and damage markers in the hippocampus, and resulted in prolongation of survival time. Delaying the onset of cooling reduced the therapeutic efficiency. The results suggest that body cooling attenuates circulatory shock and cerebral ischemia insults in heatstroke.     

Ipsapirone and ketanserin protects against circulatory shock, intracranial hypertension, and cerebral ischemia during heatstroke

We assess the effects of ipsapirone (a 5-HT1A receptor agonist), ketanserin (a 5-HT2A receptor antagonist), (-)-pindolol (a 5-HT1A receptor antagonist), and DOI (a 5-HT2A receptor agonist) on heatstroke in a rat model. Animals, under urethane anesthesia, were exposed to high ambient temperature of 42 degrees C until mean arterial pressure and local cerebral blood flow in the striatum began to decrease, which was arbitrarily defined as the onset of heatstroke. Normothermic controls were exposed to room temperature of 24 degrees C. In rats treated with normal saline immediately before the initiation of heat stress, the values for survival time were found to be 21 to 25 min. Systemic administration of ipsapirone (10 mg/kg) or ketanserin (2 mg/kg) immediately before the initiation of heat stress significantly increased the survival time to new values of 92 to 104 min. Combined treatment with ipsapirone and ketanserin had additive effects (survival time of 156-194 min). In contrast, systemic administration of (-)-pindolol (2 mg/kg) or DOI (2 mg/kg) significantly decreased the survival time to new values of 2 to 3 min. In vehicle-treated heatstroke rats, the values for core temperature, intracranial pressure, and the extracellular levels of cellular ischemia (e.g., glutamate and lactate/pyruvate ratio) or damage (e.g., glycerol) markers and neuronal damage scores in striatum were significantly higher than those of normothermic controls. On the other hand, the values for mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of O2 were significantly lower than those of normothermic controls. The heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral hypoperfusion and hypoxia, and increased levels of cellular ischemia and damage markers in striatum were all significantly attenuated by prior administration of ipsapirone or ketanserin. The present results strongly suggest that previous activation of 5-HT1A receptors or antagonism of 5-HT2A receptors protects against heatstroke by reducing circulatory shock and cerebral ischemia, whereas prior antagonism of 5-HT1A receptors or activation of 5-HT2A receptors exacerbates heatstroke.     

Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke

Objective To evaluate the effects of hypertonic (3%) saline in heatstroke rats with circulatory shock, intracranial hypertension, and cerebral ischemia.Design and setting Urethane-anesthetized rats were exposed to a high ambient temperature of 42°C until mean arterial pressure and local cerebral blood flow (CBF) in the corpus striatum began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24°C.Measurements and results Extracellular concentrations of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum of rat brain were assessed by intracerebral microdialysis methods. Striatal PO₂, temperature, and local CBF were measured with a combined OxyLite PO₂, thermocouple, and OxyFlo LDF, respectively. The values of mean arterial pressure, cerebral perfusion pressure, and striatal CBF and PO₂ in rats treated with 0.9% NaCl solution after the onset of heatstroke were all significantly lower than those in normothermic controls. In contrast, the values of intracranial pressure, brain temperature, and extracellular concentrations of glutamate, glycerol, and lactate/pyruvate in the corpus striatum were greater. Intravenous infusion of hypertonic (3%) saline solution either "0" time before the start of heat exposure or right after the onset of heatstroke significantly attenuated the heatstroke-induced arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and cerebral ischemia and damage and resulted in prolongation of survival time.Conclusions Our results strongly suggest that the experimental heatstroke syndromes can be effectively prevented and treated by hypertonic saline.An editorial regarding this article can be found in the same issue ()     

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.     

Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.     

Platonin, a cyanine photosensitizing dye, causes attenuation of circulatory shock, hypercoagulable state, and tissue ischemia during heat stroke

The aim of this study was to investigate the therapeutic effect of platonin, a cyanine photosensitizing dye as well as an inhibitor of proinflammatory cytokines, in an animal model of heat stroke. Anesthetized rats, immediately after the onset of heat stroke, were divided into two major groups and given the following: normal saline (1 mL per kg body weight) intravenously, or platonin (12.5-50 microg/mL per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heat stroke. Another group of rats was exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 18 to 22 min. Resuscitation with intravenous doses of platonin, but not normal saline, immediately at the onset of heat stroke, significantly improved survival during heat stroke (41-147 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor-alpha, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, and D-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase, and striatal levels of partial pressure of oxygen, local cerebral blood flow, glycerol, glutamate, and lactate/pyruvate were all elevated during heat stroke. The systemic inflammation, hypercoagulable state, and cerebral ischemia and injury during heat stroke were all significantly suppressed by platonin. The data demonstrate that platonin therapy may resuscitate heat stroke victims by reducing circulatory shock, systemic inflammation, hypercoagulable state, and tissue ischemia and injury.     

Heat shock pretreatment may protect against heatstroke-induced circulatory shock and cerebral ischemia by reducing oxidative stress and energy depletion

The mechanisms underlying the protective effects of heat shock pretreatment on heatstroke remain unclear. Here we attempted to ascertain whether the possible occurrence of oxidative stress and energy depletion exhibited during heatstroke can be reduced by heat shock preconditioning. In the present study, colonic temperature, mean arterial pressure, heart rate, striatal levels of heat shock protein 72 (HSP72), local Po2, brain temperature, cerebral blood flow, cellular ischemia and damage markers, dihydroxybenzoic acid (DHBA), lipid peroxidation, glutathione, glutathione peroxidase and reductase activities, and ATP were assayed in normothermic control rats and in heatstroke rats with or without preconditioning 16 or 96 h before initiation of heatstroke. Heatstroke was induced by exposing the anesthetized rats to a high ambient temperature (Ta = 43 degrees C) until the moment at which MAP decreased from its peak level. Sublethal heat shock pretreatment 16 h before initiation of heatstroke, in addition to increasing striatal HSP72 levels, conferred significant protection against heatstroke-induced arterial hypotension, striatal ischemia and damage, increment of hydroxyl radical formation, lipid peroxidation, glutathione oxidation, and decrement of glutathione peroxidase activity and ATP. However, at 96 h after heat shock, when striatal HSP72 expression returned to basal levels, the above responses that occurred during onset of heatstroke were indistinguishable between the two groups. These results suggest that heat shock pretreatment induces HSP72 overexpression in striatum and confers protection against heatstroke-induced striatal ischemia and damage by reducing oxidative stress and energy depletion.     

羟乙基淀粉对体外循环血流动力学及凝血的影响

目的 观察小儿心脏手术体外循环中预充6%羟乙基淀粉(Volven130/0.4)对血流动力学及凝血功能的影响.方法60例体外循环低温全麻心脏手术患儿,随机分为对照组(C组)和羟乙基淀粉组(V组),每组30例,C组在体外循环中预充血浆400 ml,V组在体外循环中预充羟乙基淀粉400 ml.体外循环前、后监测心率(HR)、平均动脉血压(MAP)、中心静脉压(CVP).体外循环前、后分别抽取静脉血测定:①红细胞比容(HCT),血沉(BSR);②血小板计数(PLC),凝血酶原时间(PT),激活全血凝固时间(ACT).观察术前、心肺转流15min、返回ICU时及术后24h上述指标的变化.结果 两组HCT、PLC在体外循环后均显著降低,全血血沉均显著加快,两组心率、MAP、CVP、PLC、ACT、PT体外循环前、后差异均无统计学意义(均P＞0.05).结论6%羟乙基淀粉血液稀释用于小儿心内直视手术安全有益.     

Hydroxyethyl starch normalizes platelet and leukocyte adhesion within pulmonary microcirculation during LPS-induced endotoxemia

Growing evidence supports substantial pathophysiological impact of platelets and their interactions on the development of septic lung failure. We developed a rat model of endotoxemia for direct in situ visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. Male Sprague-Dawley rats were assigned to control, endotoxemia (Escherichia coli LPS, 15 mg/kg, i.v.), and fluid management for treatment of LPS-induced hypovolemia (Ringer lactate, hydroxyethyl starch [HES] 6%) groups (n = 7 each). Leukocytes were labeled in vivo by rhodamine, and 5 x 10(6) Calcein-AM-labeled nonactivated platelets were injected. Microcirculatory parameters (vessel diameter, ventilation-perfusion ratio) and adhesive characteristics of platelets and leukocytes (velocity, rolling, sticking) within the pulmonary microcirculation were quantified after endotoxin application under various regimens of fluid substitution for 60 min. A reduction of cell velocity and enhanced cell adhesion was seen in leukocytes and platelets (P < 0.05) after LPS injection. Fluid treatment with HES 6% resulted in a significant increase of platelet's velocity compared with the LPS group (442.86 +/- 20.60 vs. 343.93 +/- 11.17; P < 0.05), whereas Ringer lactate showed no beneficial effects. Similarly, HES 6% normalized LPS-induced platelet rolling and sticking as well as alterations in ventilation-perfusion ratio. Using direct visualization of the pulmonary microcirculation, we observed that platelet and leukocyte interactions are enhanced in the lung during LPS endotoxemia. Fluid therapy with HES 6% seems to have restorative effects on these cellular functions within the pulmonary microcirculation.     

Hydroxyethyl starch inhibits neutrophil adhesion and transendothelial migration

A resuscitation strategy that significantly alters the state of neutrophil (PMN) activation may impact organ function and survivability after shock. Various resuscitative fluids have been shown to elicit a severe immune activation and an upregulation of cellular injury markers, whereas other fluids have been shown to be protective. Recent studies have demonstrated that hydroxyethyl starch (HES), an artificial colloid, may exert significant anti-inflammatory effects, whereas conflicting studies with the same substance have shown an increase in PMN activation. Successful manipulation of the early immune events associated with hemorrhage and resuscitation will require a better understanding of the possible pro- or anti-inflammatory effects of resuscitation fluids. Our study investigated the effect of HES directly on PMN and cultured vascular endothelial cells in vitro. The effect of HES on PMN surface expression of CD11b and L-selectin was measured by flow cytometry. PMN activation response to HES was measured using a shape-change assay in response to formyl-methionyl-leucyl-phenylalanine (f-MLP). The effect of HES on endothelial cell surface expression of E-selectin, P-selectin, vascular cell adhesion molecule-1(VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) was evaluated by enzyme-linked immunoabsorbant assay. PMN rolling, adhesion, and migration events were measured using direct microscopy under conditions simulating microvascular flow. PMN surface expression of CD11b and L-selectin in whole blood samples and isolated PMNs were unaffected by exposure to HES. HES had no effect on the normal f-MLP dose-dependent increase in PMN activation. In the absence of IL-1 stimulation, there was a small but statistically significant (P < 0.05) increase in ICAM-1 after exposure to HES. After stimulation with IL-1 (10 U/mL), HES had no effect on the expression of P-selectin, E-selectin, ICAM-1, or VCAM-1. Under simulated microvascular flow conditions in vitro, HES significantly diminished the PMN tethering rate (P < 0.05) and the transendothelial migration rate (P < 0.05) in a dose-dependent manner. HES significantly alters the function of the PMN at the interface of the PMN responding to activated endothelium. The effect occurs, surprisingly, without a coincident effect on the state of PMN activation or a significant change in the surface expression of the adhesion molecules responsible for PMN-endothelial interaction.     

Hydroxyethyl starch and prednisone as adjuncts to granulocyte collection

A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or HES administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.     

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)     

Pharmacotherapy of circulatory shock

The rubric "shock" encompasses a wide spectrum of critical events, which if untreated, result in morbidity and mortality. Understanding of the various forms of shock has evolved rapidly in the past 20 years as new laboratory and clinical observations have been published. In this article, the authors discuss the physiology of the shock state, review the circumstances in which shock becomes likely, and review the etiologies and diagnostic characteristics of distributive (septic, spinal, anaphylactoid/anaphylactic), cardiogenic, hypovolemic, and obstructive shock. The rationale and applications of conventional and controversial therapies are discussed. The therapeutic potentials of current lines of shock research are also discussed.     

Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heatstroke

Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.     

Blood viscosity and circulatory shock

Conclusions Rheological features of the whole blood and blood components are of potential importance for microcirculatory blood flow in circulatory shock. The relative contribution of vascular geometric and rheological factors to the resistance to blood flow in the various shock states in man, however, are hard to elucidate [73]. Blood viscosity is mainly determined by haematocrit. In low flow states RBC aggregation in the venules might sustain the arrest of flow and hamper reflow. Lowering haematocrit may be beneficial in improving microcirculatory flow in hypovolaemic conditions as haemorrhagic shock. A decrease in RBC deformability is seen in critically ill, septic patients and this may reduce capillary flow. The WBC is likely to contribute to the maldistribution of microcirculatory flow in both hypovolaemic and septic shock and might even block capillary flow. The exact contribution of changes in haematocrit, RBC aggregation, RBC deformability, WBC deformability and plasma viscosity on blood viscosity and thus (micro)circulatory flow in human shock states, especially in septic shock, remains to be elucidated.     

羟乙基淀粉高容量负荷治疗的临床效果

目的探讨在麻醉诱导期采用羟乙基淀粉（6％贺斯200／0．5，HES）行高容量负荷时，对血流动力学等方面的影响。方法随机选择ASA1-2级的患者200例，分为两组，贺斯组（n=100），林格氏溶液组（n=100）。开放静脉通路后，在30—40min内快速输入HES或林格氏溶液（LR）500，1000ml。记录麻醉诱导前（容量负荷前）、手术开始前、术中1h、术中2h及手术结束时HR、SBP、DBP。同时记录术中出血量及输血量，观察容量负荷后有无肺水肿及心衰的临床征象以及是否有异常出血的表现。结果贺斯组血流动力学更稳定。两组扩容量及扩容所用的时间，整个手术过程中的失血量及术中输血量无明显差异（P〉0．05）。结论采用HES行一定程度的高容量替代疗法能维持围麻醉期血流动力学及内环境的稳定，可避免手术时异体血的不必要输注，是一种简单、可行的节约用血方法。     

Neuronal survival and revival during and after cerebral ischemia

Factors influencing survival of neurons during ischemia and neuronal revival after ischemia are reviewed. During ischemia, biochemical and electro-physiological changes depend on residual blood flow rate: below 30 to 40 ml/100 g/min EEG amplitude decreases, below 18 ml/100 g/min spontaneous neuronal activity ceases, and below 10 ml/100 g/min cell membranes depolarize. Attempts to improve blood flow after middle cerebral artery occlusion with vasoactive drugs were not successful but there was an indication that the calcium antagonist nimodipine reduced ischemia-induced disturbances of ion homeostasis. Revival after ischemia depends mainly on post-ischemic hemodynamic factors, such as the no-reflow phenomenon or delayed post-ischemic hypoperfusion. No-reflow was successfully treated by induced hypertension, anticoagulation, and osmotherapy. Delayed post-ischemic hypoperfusion and the associated metabolic disturbances could not be ameliorated by either vasoactive drugs including prostacyclin, nor by metabolic inhibition with barbiturates and hypothermia. The disturbance of metabolic regulation of blood flow during post-ischemic hypoperfusion, therefore, remains one of the main problems of post-ischemic resuscitation.     

琥珀明胶和羟乙基淀粉注射液对大鼠肾缺血/再灌注损伤肾功能及血流动力学的影响

目的探讨输注不同血浆代用品琥珀明胶(血定安)或羟乙基淀粉注射液(贺斯)后,对大鼠肾缺血再灌注损伤肾功能及血流动力学的影响。方法建立SD大鼠肾缺血再灌注模型,并随机分为4组:假手术组(Ⅰ组)、生理盐水对照组(Ⅱ组)、血定安组(Ⅲ组)和贺斯组(Ⅳ组)。生化法检测大鼠血清肌酐(Scr)、尿素氮(Bun)、6-酮-前列腺素(6-keto-PGF1α)、血栓素B2(TXB2)水平并计算血栓素/6-酮-前列腺素(TXB2/6-keto-PGF1α)水平,Ⅱ、Ⅲ、Ⅳ三组大鼠监测术中血压及心率的变化情况。结果与Ⅰ组比较,Ⅱ、Ⅲ、Ⅳ三组肾动脉开放再灌注24 h后Scr、Bun、TXB2和TXB2/6-keto-PGF1α水平升高(P<0.01),与Ⅱ组比较Ⅲ、Ⅳ二组平均动脉压(MAP)水平升高(P<0.05)。结论血定安和贺斯对大鼠肾缺血再灌注损伤肾功能损害的影响没有显著性差异而在维持血流动力学稳定方面有明显作用。     

Local attenuation of systemically mediated splanchnic vasoconstriction during shock due to cholera

Hypovolemic shock, most often due to hemorrhage, is typically associated with intense splanchnic vasoconstriction. This can be severe enough to impair the functional and structural integrity of the gastrointestinal tract. Paradoxically, with cholera the structure of the gastrointestinal tract is preserved, and the intestine continues to secrete fluid delivered to it in the circulating blood in spite of severe hypovolemic shock. This suggests that splanchnic blood flow is maintained at higher levels in hypovolemic shock due to cholera than in hypovolemic shock due to hemorrhage. Our hypothesis is that cholera toxin in the intestinal lumen activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction. Blood flow to an isolated ileal segment in situ in the anesthetized rabbit was measured continuously (ultrasound transit-time volume flow probe) for 5 to 6 h after instillation of cholera toxin into the isolated intestinal lumen. Norepinephrine was infused selectively into the mesenteric artery supplying the segment to elicit local responses uncomplicated by compensatory changes secondary to systemic effects of norepinephrine. Baseline vascular conductance increased gradually and became significantly greater in cholera toxin experiments than in vehicle experiments 5 h after treatment (P < 0.035). Animals treated with cholera toxin were less responsive to norepinephrine than vehicle treated animals were (P < 0.05) and became more so over time (P < 0.001). Our conclusion is that cholera toxin activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction, at least in part by reducing vascular responsiveness to a systemic vasoconstrictor, norepinephrine.