Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate and free radicals in heatstroke rats

In the present study, we attempted to assess the mechanisms underlying the neuroprotective effect of hypervolaemic haemodilution in rat heatstroke. In anaesthetized rats treated with normal saline (NS) immediately after the onset of heatstroke induced by T (a) (ambient temperature) of 42 degrees C for 88 min, followed by T (a) of 24 degrees C for 12 min, the values for MAP (mean arterial pressure), ICP (intracranial pressure), CPP (cerebral perfusion pressure), CBF (cerebral blood blow), brain P O(2) (partial pressure of O(2)) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 42+/-3 mmHg, 33+/-3 mmHg, 9+/-3 mmHg, 109+/-20 BPU (blood perfusion units), 6+/-1 mmHg, 51+/-7 micromol/l, 24+/-3 micromol/l, 124+/-32, 694+/-22% of baseline and 2.25+/-0.05 respectively. In animals treated with 10% albumin immediately after the onset of heatstroke ( T (a) of 42 degrees C for 88 min), the values for MAP, ICP, CPP, CBF, brain P O(2) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 64+/-6 mmHg, 10+/-2 mmHg, 54+/-5 mmHg, 452+/-75 BPU, 15+/-2 mmHg, 3+/-2 micromol/l, 4+/-2 micromol/l, 7+/-3, 119+/-7% of baseline and 0.38+/-0.05 respectively. Apparently, the heatstroke-induced arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischaemia, brain hypoxia, increased levels of striatal glutamate, glycerol, lactate/pyruvate ratio and hydroxyl radicals, and increased striatal neuronal damage score values were all attenuated significantly by the induction of hypervolaemic haemodilution in rats immediately at the onset of heatstroke. These results demonstrate that the neuroprotective effect of hypervolaemic haemodilution is associated with a decrease in the elevation of glutamate, glycerol, lactate and free radicals in brain exposed to experimental heatstroke-induced cerebral ischaemia/hypoxia 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.     

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.     

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 ()     

Hydroxyethyl starch produces attenuation of circulatory shock and cerebral ischemia during heatstroke

We hypothesized that hydroxyethyl starch (HES), which maintains colloid osmotic pressure and potentially "seals" capillary leaks, would ameliorate circulatory shock and cerebral ischemia during heatstroke in a rat model. Animals under urethane anesthesia were exposed to high ambient temperature (Ta) of 42 degrees C until mean arterial pressure and local cerebral blood flow in the striatum began to decrease from peak level, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24 degrees C. In rats treated with 1 mL/kg, 11 mL/kg, or 22 mL/kg of normal saline (NS) immediately after the onset of heatstroke, the values for survival time (interval between the initiation of heatstroke and animal death) were found to be 21 +/- 2, 36 +/- 9, or 92 +/- 7 min, respectively. Intravenous administration of 11 mL/kg of HES (about 5 times the volume-expanding effect of 11 mL/kg of NS), but not 2 mL/kg of HES (about the same volume-expanding effect as 11 mL/kg NS), significantly increased the survival time from the control values of 36 +/- 9 min to new values of 181 +/- 13 min. In NS (11 mL/kg)-treated or HES (2 mL/kg)-treated rats after heatstroke onset, the values for mean arterial pressure, stroke volume, total peripheral resistance, cerebral blood flow, blood pH, Paco2, Pao2, and brain Po2 were significantly lower than those of rats kept at Ta 24 degrees C. In contrast, the values for colonic temperature and the extracellular concentrations of glutamate, glycerol, and lactate/pyruvate ratio obtained in striatum were significantly higher than those of controls. The heatstroke-induced arterial hypotension, decreased stroke volume and total peripheral resistance, decreased blood pH and Pao2, decreased brain Po2, and increased levels of striatal glutamate, glycerol, and lactate/pyruvate ratio in NS-treated rats were all attenuated significantly by increasing the volume expansion with 11 mL/kg of HES administered immediately at the onset of heatstroke. Our data suggest that HES therapy seems superior to NS treatment during heatstroke. The benefit of HES therapy during heatstroke might have something to do with volume expansion rather than capillary permeability.     

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.     

Dopamine and neurotensin storage in colocalized and noncolocalized neuronal populations

The effects of reserpine on dopamine (DA) and neurotensin (NT) levels were studied in four different brain regions of the rat. Reserpine (0.5-5.0 mg/kg i.p., 6, 18, 48 and 72 hr) produced a dose- and time-dependent decrease in both DA and NT levels in the prefrontal cortex, a brain region innervated by a mixed DA/NT projection. The effect of reserpine was not mimicked by alpha-methylparatyrosine (200 mg/kg i.p.) pretreatment. Furthermore, the reserpine-induced decline in prefrontal cortex DA and NT levels occurred after gamma-butyrolactone (GBL)-induced inhibition of impulse flow (750 mg/kg i.p.). In contrast, in the nucleus accumbens and striatum, regions which contain colocalized (nucleus accumbens) and intrinsic (striatum and nucleus accumbens) neurotensin perikarya, reserpine produced declines in DA and increases in NT levels. alpha-Methylparatyrosine decreased striatal and nucleus accumbens DA levels without altering NT levels in these structures. GBL produced an increase in DA levels in the nucleus accumbens and striatum while decreasing nucleus accumbens and striatal NT levels. Reserpine attenuated the decline in nucleus accumbens and striatal NT levels produced by GBL. In the periaqueductal grey, a brain region densely innervated by NT which has a small population of DA perikarya, reserpine had no effect on NT levels. Because there is no known colocalization of DA and NT in the striatum, the increases in striatal NT levels after depletion of DA may indicate that striatal DA afferents control the release and/or synthesis of NT within NT cells in the striatum, thus leading to alterations in striatal tissue levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resuscitation from experimental heatstroke by hyperbaric oxygen therapy

OBJECTIVE: Heatstroke is characterized by hyperthermia, vasoplegic shock, and cerebral ischemia and hypoxia. Hyperbaric oxygen (HBO) has been shown to reduce brain ischemia and behavioral dysfunction during cerebral artery occlusion. The efficacy of HBO therapy for resuscitation from heatstroke remains to be determined in the laboratory. DESIGN: Anesthetized rats were randomized to several groups and administered: 1) no resuscitation (normobaric air) after onset of heatstroke, 2) HBO for 1 hr (100% oxygen at 253 kPa for 1 hr), 3) cyclic HBO intermitted by a 5-min air break for 1 hr of treatment (100% oxygen at 253 kPa), 4) hyperbaric air (air at 253 kPa for 1 hr), 5) normobaric hyperoxia (100% oxygen at 101 kPa for 1 hr), or 6) 8% HBO (hyperbaric 8% oxygen at 253 kPa for 1 hr). SETTING: Laboratory investigation. SUBJECTS: Sprague-Dawley rats (300- to 400-g males). INTERVENTIONS: Rats were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their colonic temperature; mean arterial pressure; heart rate; arterial blood levels of pH, Paco2, Pao2, So2%, and tumor necrosis factor-alpha; the cortical levels of ischemic and damage markers, and cortical neuronal damage scores were determined. The moment at which mean arterial pressure began to decrease from peak levels was arbitrarily taken as the onset of heatstroke. MAIN RESULTS: Survival time (interval between onset of heatstroke and animal death) was 19 +/- 1 (n = 10), 131 +/- 18 (n = 14), 159 +/- 28 (n = 13), 72 +/- 14 (n = 10), 68 +/- 12 (n = 10), and 45 +/- 11 (n = 10) mins, respectively, for normobaric air, HBO for 1 hr, cyclic HBO, hyperbaric air, normobaric hyperoxia, and 8% HBO groups. The heatstroke induced arterial hypotension and bradycardia, decreased arterial levels of pH, Pao2, and So2%, increased arterial levels of tumor necrosis factor-alpha, and increased values of cellular ischemia and damage markers. In addition, neuronal damage scores in the cortex were significantly reduced by HBO for 1 hr and cyclic HBO resuscitation. CONCLUSION: We successfully demonstrated that HBO and, to some extent, hyperbaric air, normobaric hyperoxia, or HBO 8% was found beneficial in resuscitating rats with experimental heatstroke. HBO effectively reduced heatstroke-induced arterial hypotension, hypoxia, plasma tumor necrosis factor-alpha overproduction, and cerebral ischemia and damage and improved survival.     

Sustained high release at rapid stimulation rates and reduced functional autoreceptors characterize prefrontal cortex dopamine terminals

The release of dopamine (DA) from mesocortical and nigrostriatal nerve terminal fields, as well as its modulation by auto- and heteroreceptors was investigated. Rabbit brain slices obtained from medial prefrontal cortex (PFC) and nucleus caudate (striatum) were prelabeled with [3H]DA in the presence of 0.3 microM desipramine. Neuronal depolarization was elicited by electrical stimulation. Higher stimulation-evoked overflow of [3H]DA (release) was observed from PFC than from striatal slices. At 0.3 Hz (120 pulses) release from the PFC was 60% higher than from the striatum, and at higher frequencies (10 Hz and 120 or 1200 pulses) the fraction of tissue radioactivity released from the PFC was 550% greater than that released from the striatum. These differences were not eliminated by blockade of autoreceptors with haloperidol, or by inhibition of neuronal uptake with nomifensine. These results suggest that the coupling between neuronal depolarization and DA release is more efficient in the PFC than in the striatum. This may allow the PFC terminals to sustain neurotransmission under continuous fast firing. Selective D2 agonists, as well as nonselective DA agonists, inhibited DA release in a concentration-dependent fashion from the PFC and the striatum. Their effects were blocked by l-sulpiride or haloperidol. SKF 38393, a selective D1 agonist, produced a small facilitation of release from both regions; its effects were blocked by SCH 23390 (a selective D1 antagonist). The latter was ineffective on its own. The maximal degree of inhibition of release produced by apomorphine, bromocriptine and LY-171555 was lower in the PFC than in the striatum; these differences were accentuated greatly at high stimulation rates. When the slices were stimulated at frequencies comparable to the "in vivo" firing rates for each neuronal group, apomorphine and LY-171555 were much weaker in inhibiting DA release from the PFC (10 Hz) than from the striatum (3 Hz). In the striatum, strong modulation of DA release by endogenous DA was observed; whereas little modulation was seen in the PFC. Nomifensine produced larger increases in the stimulation-evoked overflow of DA from PFC and there was no synergistic interaction between nomifensine and haloperidol in this structure. In the striatum, marked facilitation of DA overflow was observed when nomifensine and haloperidol were given together. Furthermore, haloperidol per se facilitated DA release from both brain regions; however, the degree of facilitation was frequency dependent in the striatum, but not in the PFC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hypothermic retrograde jugular vein flush in heatstroke rats provides brain protection by maintaining cerebral blood flow but not by hemodilution

OBJECTIVE: To determine the fundamental mechanism of brain protection by hypothermic retrograde jugular vein flush (HRJVF) in heatstroke rats. DESIGN: Randomized, controlled, and prospective study. SETTING: University physiology research laboratory. SUBJECTS: Sprague-Dawley rats (270-320 g, males). INTERVENTIONS: Rats were randomized into four groups as follows: a) normothermic control (NC, n = 8); b) heatstroke rats without cold saline delivery (HS, n = 8); c) heatstroke rats treated with cold saline via femoral vein (HS+F, n = 8); and d) heatstroke rats treated with HRJVF (HS+J, n = 8). Right external jugular vein and right femoral vein were cannulated in each rat. The cannulation in the jugular vein was with cranial direction. To produce heatstroke, rats were placed in a chamber with an ambient temperature of 43 degrees C. The cold saline (4 degrees C, 1.7 mL/100 g) was delivered via the cannula in either the femoral vein or jugular vein immediately after the onset of heatstroke. Glutamate release in the brain, cerebral blood flow (CBF), and hematocrit of arterial blood were determined. MEASUREMENTS AND MAIN RESULTS: After onset of heatstroke, HRJVF significantly decreased the glutamate release. In contrast, cold saline delivery via femoral vein could only delay the elevation of glutamate release in the brain. The CBF of HS and HS+F rats decreased rapidly after the onset of heatstroke, but the CBF of HS+J rats was initially elevated by HRJVF and was maintained at baseline 30 mins after onset of heatstroke. Hematocrit in all the rats did not change after testing. CONCLUSIONS: HRJVF protects the brain by maintaining cerebral blood flow in rats after heatstroke. To preserve brain function and prolong survival after severe heatstroke, maintenance of cerebral blood flow is important in the management of heatstroke.     

L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.     

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.     

术前应用6%羟乙基淀粉行急性高容量血液稀释对老年患者动脉压及氧代谢的影响

目的：探讨应用6％羟乙基淀粉行急性高容量血液稀释（AHH）对老年患者动脉压和氧代谢的影响。方法：随机选择腹部择期手术的老年患者40例,随机分为两组,A组为高容量血液稀释组,B组为非血液稀释组。B组入室后补充基础生理需要量及禁食丧失需要量。A组患者以25ml／min的速率输入6％羟乙基淀粉7ml／kg后诱导,同时继续输入达15ml／kg行高容量血液稀释,分别监测记录基础值（T0）、诱导后插管前（T1）、插管后即刻（T2）、插管后5min（T3）、10min（T4）、20min（T5）、切皮前（L6）的平均动脉压（MAP）、心率（HR）、中心静脉压（CVP）。经桡动脉取血测血气、Lac。结果：A组患者诱导前后MAP无显著性差异（P〉0．05）,B组诱导后MAP显著降低（P〈0．05）。与同时相A组比较有显著性差异（P〈0．05）。A组CVP插管后5min（T3）与基础值（T0）比较有显著性差异（P〈0．05）。与同时相B组比较有显著性差异（P〈0．05）,两组患者HR诱导后减慢（P〈0．05）。A组血红蛋白（Hb）、细胞压积（Hct）在血液稀释后显著降低（P〈0．05）。两组血气、Lac在血液稀释前后无显著性变化（P〉0．05）。结论：适度AHH有利于维持老年患者血液动力学的稳定,而氧代谢改变不明显,值得临床推广。     

Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat

Injection of an adenoviral (Ad) vector encoding human glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic (DA) neurons in the substantia nigra (SN) of young rats. As Parkinson's disease occurs primarily in aged populations, we examined whether chronic biosynthesis of GDNF, achieved by adenovirus-mediated delivery of a GDNF gene (AdGDNF), can protect DA neurons and improve DA-dependent behavioral function in aged (20 months) rats with progressive 6-OHDA lesions of the nigrostriatal projection. Furthermore, the differential effects of injecting AdGDNF either near DA cell bodies in the SN or at DA terminals in the striatum were compared. AdGDNF or control vector was injected unilaterally into either the striatum or SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the same side as the vector injection. AdGDNF injection into either the striatum or SN significantly reduced the loss of FG labelled DA neurons 5 weeks after lesion (P 相似文献   

Infusion therapy tactics during prolonged reconstructive and plastic surgery using microsurgical techniques]

The impact of various infusion therapy techniques has been studied in 166 patients during microsurgery for posttraumatic tissue defects. It has been established that the achievement of hypervolemic hemodilution is accompanied by the damage of water-electrolyte homeostasis and peripheral circulation during the operation and on the first postoperative day. Normovolemic hemodilution makes it possible to prevent the above disturbances and optimize peripheral blood flow in case the infusion programme is compiled adequately with an obligatory introduction of blood plasma preparations.     

Differential effects of phorbol ester on prefrontal cortex and striatal dopamine terminals: dependence on rate and duration of stimulation

Compared to the nigrostriatal dopamine (DA) neurons, the mesocortical DA neurons projecting to the prefrontal cortex (PFC) are able to sustain higher levels of release when driven at high stimulation frequencies. The effect of a well known activator of protein kinase C (PKC), 4-beta-phorbol-12, 13-dibutyrate (PDBu), were compared on PFC and striatal DA terminals. DA release was monitored from slices of the rabbit PFC and striatum obtained from the same animal. The PKC activator, PDBu (30-1000 nM) enhanced the stimulation-evoked release (SER) of DA from PFC and striatum. The magnitude of the facilitation of DA release produced by PDBu was much greater from the PFC than from the striatum. In the striatum, PDBu produced a bell-shaped dose-response curve, i.e., 0.03 and 1 microM PDBu enhanced SER of DA by 25%, whereas 0.1 and 0.3 microM PDBu enhanced DA release by 60 and 100%, respectively (1 Hz, 120 pulses). In the PFC, 0.03 microM enhanced the SER of DA by 70% and 1 microM by 250% (1 Hz, 120 pulses). In addition, in the PFC, PDBu enhance the basal release of DA (+65% at 1 microM); this effect was not seen in the striatum. The inactive isomer, 4-alpha-phorbol-12, 13-dibutyrate (0.03-1 microM) failed to increase the SER and the basal release of DA from PFC or striatum. The SER of DA was dependent on the rate and duration of stimulation. However, under all conditions of stimulation studied DA release from PFC was always greater than from the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs

The effects of opioid agonists with selectivity for kappa, mu and delta types of opioid receptors on the K+-stimulated release of [3H]dopamine (DA) from striatum and cortex of rat and guinea pig loaded previously with the monoamine have been studied. The kappa agonist U50488H did not affect base-line release of [3H]DA measured in 5 mM K+, but produced a dose-dependent inhibition of the release of [3H]DA stimulated by 20 mM K+ from slices of striatum in rat and guinea pig, with an IC50 of about 0.5 nM in each case. In contrast, the mu-selective agonist, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol, and the delta-selective agonist, [D-Pen2-D-Pen5]enkephalin, did not inhibit stimulated release from the slice preparations at concentrations up to 1 microM. The inhibitory effects of U50488H were antagonized by naloxone, and the potent and selective kappa antagonist, nor-binaltorphimine (nor-BNI). Similar results were obtained when release of [3H]DA from rat and guinea pig cortex slices was examined. In guinea pig cortex, the maximum inhibition of DA release induced by U50488H was 80% of control-stimulated fractional release. In rat cortex and in striatum of both species the maximum release was about 40% of control fractional release. Thus, in the guinea pig, the mesocortical dopaminergic pathway appears more sensitive to the inhibitory effects of U50488H than the nigrostriatal system. The effects of the opioids on the K+ (12.5 mM)-stimulated release of [3H]DA from guinea pig striatal synaptosomes also were determined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneous dopamine neurochemistry in the striatum: the fountain-drain matrix

In contrast to the relatively high attention paid to the structural heterogeneity of striatal dopamine (DA) innervation, little attention has been focused on the possible striatal heterogeneity for release and uptake of DA. By using amperometric methods, we found striatal regions showing a DA decrease during the medial forebrain bundle stimulation (drain areas) near to other zones that showed an increase in DA concentration (fountain areas). Both areas were intermixed to form a tridimensional matrix to regulate DA concentration throughout the striatum (fountain-drain matrix). The response to electrical stimuli of different amplitudes and durations and to different drugs (alpha-methyl-l-tyrosine, cocaine, gamma-butyrolactone, and haloperidol) suggests that regional differences for both DA release/DA uptake and DA cell firing autoregulation are behind the striatal fountain-drain matrix. The high diversity of DA activity observed in the striatum is a new framework for analyzing experimental and clinical phenomena.     

Comparative dopamine-cholinergic mechanisms in the olfactory tubercle and the striatum: effects of metoclopramide

The olfactory tubercle (OT) is a limbic structure containing high dopamine (DA) and acetylcholine (ACh) concentrations. We performed a comparative study of the DA-ACh interactions, the efficacy of autoreceptor control and the effects of metoclopramide in the OT and the nucleus caudate (striatum). Rabbit brain slices from both regions of the same animal were prelabeled with radioactive DA and/or choline and then superfused. Comparable magnitude of DA and ACh release was evoked by electrical stimulation from both regions. DA release was unaltered, whereas ACh release was inversely related to the stimulation frequency, both in OT and striatum. Apomorphine (APO), a D1-D2 agonist, an LY-171555 (LY), a D2 agonist, inhibited DA and ACh release from OT and striatum with similar EC50 and Emax (maximal percentage of inhibition). However, the maximal degree of inhibition of ACh release achieved with APO, LY or DA in the OT was only one-half that observed in the striatum. In both regions, the inhibitory effects of DA agonists on DA and ACh release were reduced markedly when the number of electrical pulses and/or the frequency of stimulation were increased. l-Sulpiride, a DA D2 antagonist, increased the evoked release of DA and ACh from OT in direct relationship with the frequency of stimulation. In the OT, increases in synaptic DA achieved by administration of amphetamine or by blockade of the neuronal uptake pump with nomifensine inhibited the evoked release of ACh. Again these drug treatments produced only a 40 to 50% inhibition of ACh release. SKF 38393, a D1 agonist, had no effect per se on DA or ACh release in OT slices from control or from reserpine-treated animals (2 mg/kg s.c. for 3 or 7 days). With the exception of one specific dose combination, coadministration of SKF 38393 and LY produced no additive or synergistic effects on DA or ACh release from OT. APO- and LY-induced inhibition of DA and ACh release were antagonized by l-sulpiride. However, 300 nM SCH 23390, a D1 antagonist, reduced APO inhibition of DA and ACh release without affecting the inhibitory action of LY on DA and ACh release. Metoclopramide, "a DA antagonist with poor limbic activity", had a similar affinity for OT (pA2: 7.59) and striatal (pA2: 7.59) DA autoreceptors. Its antidopaminergic efficacy on DA receptors modulating ACh release from OT and striatum was also compared.(ABSTRACT TRUNCATED AT 400 WORDS)     

Regulation of glutamate release by α7 nicotinic receptors: differential role in methamphetamine-induced damage to dopaminergic and serotonergic terminals

Regulation of glutamate release is an important underlying mechanism in mediating excitotoxic events such as damage to dopamine (DA) and serotonin (5-HT) neurons observed after exposure to methamphetamine (Meth). One way to regulate glutamate release may be through the modulation of α7 nicotinic acetylcholine (nACh) receptors. Meth administration is known to increase acetylcholine release; however, it is unknown whether Meth increases glutamate release and causes long-term damage to both DA and 5-HT terminals through the activation of α7 nACh receptors. To test this hypothesis, the α7 nACh receptor antagonist, methyllycaconitine (MLA), was administered before the administration of repeated doses of Meth while simultaneously monitoring extracellular striatal glutamate with in vivo microdialysis. In addition, the subsequent long-term decreases in markers of dopaminergic and serotonergic terminals, including DA reuptake transporter (DAT), serotonin reuptake transporter (SERT), vesicular monoamine transporter-2, vesicular DA, and vesicular 5-HT content in the rat striatum, were measured. The results show that MLA pretreatment prevented Meth-induced increases in striatal glutamate and protected against the subsequent long-term decreases in striatal DAT and vesicular DA content without affecting the hyperthermia produced by Meth. In contrast, the Meth-induced decreases in striatal SERT immunoreactivity and vesicular 5-HT content were not affected by MLA. This suggests that the α7 nACh receptor differentially mediates glutamate-dependent damage to DA but not 5-HT terminals in a manner that is independent of hyperthermia. Furthermore, antagonism of α7 nACh receptors may be a possible therapeutic strategy for decreasing extracellular glutamate and preventing the excitotoxic damage observed in other DA-related neurodegenerative disorders.