Regional changes in cerebral extracellular glucose and lactate concentrations following severe cortical impact injury and secondary ischemia in rats

Traumatic brain injury (TBI) causes the brain to be more susceptible to secondary insults, and the occurrence of a secondary insult after trauma increases the damage that develops in the brain. To study the synergistic effect of trauma and ischemia on brain energy metabolites, regional changes in the extracellular concentrations of glucose and lactate following a severe cortical impact injury were measured employing a microdialysis technique. Three microdialysis probes were placed in center of the impact site, in an area adjacent to the impact site, and in the contralateral parietal cortex, and perfused with artificial cerebrospinal fluid (CSF) at 2 microl/min. Rats were assigned to one of the following experimental groups (n = 7 per group): (1) combined impact injury and secondary insult, (2) impact injury with sham secondary insult, (3) sham impact with secondary insult, or (4) sham impact and sham secondary insult. The impact injury was produced with a pneumatic impactor (5 m/sec, 3-mm deformation). One hour following the impact injury, a secondary insult was produced by bilateral carotid occlusion for 1 h. The impact injury resulted in a three- to fivefold global increase in dialysate lactate concentrations, with a corresponding fall in dialysate glucose concentration by 50% compared to no change in lactate or glucose concentrations in sham-injured animals (p < .0001 for both lactate and glucose). The secondary insult resulted in a second increase in dialysate lactate and decrease in dialysate glucose concentration that was significantly greater in the animals that had suffered the impact injury than in the sham-injured animals. Ischemia and traumatic injury have synergistic effects on lactate accumulation and on glucose depletion in the brain that probably reflects persisting ischemia, but may also indicate mitochondrial abnormalities and inhibition of oxidative metabolism.     

Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose- and saline-infused rats.

To assess the effect of a glucose infusion on brain extracellular fluid (ECF) during systemic hypoxia, changes in glucose and lactate concentrations in cerebral ECF during and after moderate hypoxic hypoxia were measured in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were given either saline (n = 6) or 50% glucose solution (n = 6) for 3 h, starting 60 min before the onset of hypoxia. Hypoxia was produced by circulating 7% O2 gas in a plastic chamber for 90 min. In saline-infused animals, brain ECF glucose concentrations decreased slightly during hypoxia, although blood glucose concentrations did not change. Blood lactate concentrations increased to 6.28 +/- 0.91 mM, at 60 min after the onset of hypoxia (P less than 0.05). Brain ECF lactate concentrations increased to 3.53 +/- 0.20 mM and remained constant during 60 min of steady-state hypoxia (P less than 0.05) and decreased to the basal level within 60 min after the end of hypoxia. When sodium lactate solution was infused intravenously for 90 min (n = 4), blood lactate concentrations increased to a level as high as those found during hypoxia. However, the brain ECF lactate concentration increased only to 1.86 +/- 0.09 mM. In glucose-infused animals, the blood glucose concentration reached 339.1 +/- 32.3 mg/dl at the end of the glucose infusion, and the brain ECF glucose concentration increased to 54.7 +/- 7.3 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats

BACKGROUND: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. METHODS: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. RESULTS: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. CONCLUSION: Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.     

高晶体-高胶体渗透压混合液对失血性休克时大鼠脑血流及脑组织含水量的影响

目的 比较HHS和乳酸林格氏平衡液（LR）对大鼠失血性休克模型脑血流和脑组织含水量的影响。方法 14只大鼠随机分为2组,采用动脉放血的方法复制失血性休克模型。分别在休克后输入LR或HHS。于休克前、休克后、容量复苏后即刻和30min测其脑血流量和脑组织含水量。脑血流是采用^99mTc标记同位素法测定,脑组织含水量用烘干前后称重的方法测定。结果 容量复苏后即刻,二级动物脑血流量增加（P＜0．05）。30min后,LR组的脑血流量降低,明显低于复苏后即刻的脑血流量和同时刻HHS组的脑血流量（P＜0．05）。HHS组则无明显减少。HHS组脑组织含水量在复苏后降低（P＜0．05）,LR组动物的脑组织含水量则增加（P＜0．05）。结论 小容量HHS可增加脑出流量、减轻休克后脑组织水肿。LR不能有效地恢复脑血流量,并且可加重脑组织水肿。     

Preservation of the cortical somatosensory-evoked potential during dexmedetomidine infusion in rats

Successful somatosensory-evoked potential (SEP) monitoring has been performed during the administration of dexmedetomidine to patients, but a systematic investigation of the dose response of the SEP to dexmedetomidine has not been reported. In this study, we evaluated the effect of a range of dexmedetomidine doses on the cortical SEP in rats. Twelve rats were initially anesthetized with ketamine and the lungs were mechanically ventilated. Femoral arterial and venous catheters were placed. Anesthesia was maintained with constant infusions of remifentanil (5-15 microg. kg(-1). min(-1)) and vecuronium (56 microg. kg(-1). min(-1)). Dexmedetomidine was infused at 0.1, 0.25, 0.5, 1.0, and 2.0 microg. kg(-1). min(-1) in a stepwise manner with 10-min infusion periods at each step. In eight rats, an additional large-dose infusion of dexmedetomidine at 10 microg. kg(-1). min(-1) was administered for 30 min. The cortical SEPs were recorded after stimulation of the tibial nerve. At all infusion rates, there was a statistically insignificant increase in the SEP amplitude. Dexmedetomidine consistently increased the SEP latency, but these increases were not statistically significant. These data demonstrate that dexmedetomidine maintains technically adequate conditions for SEP monitoring in rats and provides support for future studies of the effect of dexmedetomidine on SEP monitoring in humans. IMPLICATIONS: In rats, the administration of a wide range of infusion rates of dexmedetomidine did not significantly affect the somatosensory-evoked potential. These results suggest that dexmedetomidine might be a useful adjunctive drug in patients undergoing intraoperative somatosensory-evoked potential monitoring.     

电针对脑缺血-再灌注大鼠颈静脉血糖和乳酸的影响

目的 观察电针对脑缺血-再灌注(I-R)损伤大鼠血糖和乳酸的影响.方法 雄性SD大鼠40只,随机均分为五组:水合氯醛+脑I-R组(A组)、水合氯醛+脑I-R+电针组(B组)、丙泊酚+脑I-R组(C组)、丙泊酚+脑I-R+电针组(D组)、假手术组(E组),每组8只.采用四血管阻塞法建立大鼠全脑缺血模型.于再灌注开始后,B、D组电针百会、命门和足二里穴.电针频率30～50Hz,间断疏密波,电流强度1 mA,以局部肌肉轻微震颤为度.时间20 min.在缺血后24 h,右颈静脉抽取0.5 ml血样测定血糖和乳酸.结果 A组、C组大鼠的血糖显著高于E组(P<0.05或P<0.01),乳酸则低于E组(P<0.01).与A组相比,B组和D组的血糖显著降低(P<0.01).而乳酸显著升高(P<0.01);C组血糖明显低于A组(P<0.05).结论 针刺治疗可明显改善脑I-R大鼠的糖代谢,增加腩细胞对葡萄糖的摄取和利用,水合氯醛和丙泊酚对电针信号传导的影响均无明显差异.     

Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction

OBJECTIVE: Acute unilateral ureteral obstruction (UUO) leads to changes in kidney function and metabolism. Microdialysis offers the possibility of topical analysis of changes in kidney metabolism. We applied microdialysis to the porcine kidney and evaluated its impact on gross kidney function. Furthermore, we investigated regional variations in renal interstitial fluid (RIF) glucose, lactate and urea during acute UUO. MATERIAL AND METHODS: Eight anesthetized pigs were used. Microdialysis probes were inserted in the upper, middle and lower thirds of the left renal cortex and perfused with Ringer's chloride at a rate of 0.3 microl/min. Dialysates were fractionated for 30-min periods. Bilateral intrapelvic pressure, urinary output, urinary osmolality, the excretion fractions of sodium and potassium, renal blood flow and the glomerular filtration rate were measured. Subsequently, left-sided graded ureteral obstruction was initiated, using the kidney's own urine production as a counter-pressure. RESULTS: The application of three microdialysis probes did not have any impact on kidney function. Ureteral obstruction decreased RIF glucose in the upper and lower thirds of the kidney, but not in the middle third. RIF lactate did not change. Interstitial urea increased in all regions of the kidney, but most markedly in the upper and lower poles. CONCLUSIONS: Microdialysis is of potential value for assessing the renal interstitial milieu under different pathophysiological conditions. Ureteral obstruction resulted in regional differences in cortical metabolites, predominantly affecting the upper and lower poles.     

The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats

Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.     

Intraoperative glucose infusion and blood lactate: endocrine and metabolic relationships during abdominal aortic surgery

The hypothesis that increased intraoperative blood lactate depends both on intraoperative glucose supply and inadequate tissue oxygenation occurring during surgery was tested in anesthetized patients undergoing infrarenal abdominal aortic surgery. Twenty surgical patients received either Ringer's solution or 5% glucose solution for intraoperative volume loading. Arterial blood lactate, arterial glucose, hemodynamic variables, insulin, glucagon, cortisol, epinephrine, and norepinephrine were determined preoperatively and intraoperatively. There were no significant changes in hemodynamic values, glucagon, norepinephrine, and epinephrine compared with control values in both groups. Oxygen consumption decreased only during aortic clamping. Cortisol and lactate increased significantly 10 min after aortic clamping until the end in both groups. Glucose 5% solution infusion resulted in significantly greater blood lactate accumulation and significantly greater blood glucose and insulin levels, whereas there were no changes in the patients receiving Ringer's solution. From control until aortic clamping, lactate and glucose were significantly correlated with each other in both groups; after aortic clamping until the end of the procedure, the correlation remained constant in patients in the Ringer's group, whereas no relationship could be demonstrated in those in the glucose group. The authors conclude that intraoperative glucose administration increases intraoperative blood lactate and that blood lactate accumulation depends both on glucose supply and tissue oxygen deficit. Furthermore, none of the hemodynamic metabolic and endocrine factors were reliable for assessing tissue perfusion and metabolic demands during surgery.     

Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats

Background. In cerebral ischaemia, hyperglycaemia brings aboutsevere lactate accumulation and neuronal damage when comparedwith normoglycaemia. Propofol has been known to suppress glucosemetabolism in the brain and possess neuroprotective propertiesin cerebral ischaemia. Therefore, in this study we examinedif propofol could attenuate lactate accumulation and neuronaldamage in cerebral ischaemia under hyperglycaemic conditions. Methods. Ten male wistar rats were divided into two experimentalgroups: low-dose (     

体外循环期间尼莫地平对脑糖代谢的影响

目的　研究体外循环 ( CPB)中尼莫地平对脑糖代谢的影响。方法　选择 3 1例心脏直视手术病人 ,随机分为对照组 11例 ,观察组 2 0例。尼莫地平 4 0μg· kg- 1 于 CPB始缓慢注入体外循环机中 ,测定不同时期两组病人的动脉、颈内静脉上球部的血糖、丙酮酸、乳酸和乳酸脱氢酶 ( L DH) ,计算出脑糖摄取 GL U( a- v)、乳酸净剩余 ( L v- a)值。结果　 CPB过程中两组动脉、颈内静脉上球部的血糖、丙酮酸、乳酸和 L DH均进行性升高 ,两组 GL U( a- v)均低于 CPB前 ,但观察组明显高于对照组 ,两组L v- a无显著差异。结论　 CPB中尼莫地平明显提高脑糖利用 ,产生较多的能量以维持脑细胞功能的正常     

Effect of the alpha2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats

BACKGROUND: This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone. METHODS: Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 microg/kg; infusion: 25 microg x kg(-1) x h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 microg/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and pH were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography. RESULTS: During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia. CONCLUSIONS: The current data show that the increase of circulating catecholamine concentrations during cerebral ischemia was suppressed with dexmedetomidine. In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia. This suggests that the neuroprotective effects of dexmedetomidine are not related to inhibition of presynaptic norepinephrine or glutamate release in the brain.     

Influence of nitric oxide on cerebral hemodynamics during endotoxemia in dogs

The aim of this study is to clarify the influence of nitric oxide (NO) in cerebral circulation during endotoxemia. Two groups of 24 mongrel dogs (N = 12 each) received saline 1 ml.kg-1.h-1 or endotoxin (lipopolysaccharide, LPS) 500 ng.kg-1.h-1 for 3 hours. To determine changes of NO in the systemic and cerebral circulation, we measured NOx (NO2-/NO3-) in the femoral artery and superior sagittal sinus as metabolites of NO using the Griess method. We also measured the concentrations of cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (total Hb) and cytochrome aa3 (Cytaa3) using near-infrared laser spectroscopy. Changes in cerebral blood volume were evaluated from the total Hb. NOx in systemic and cerebral circulation increased significantly after infusion of LPS. Therefore, the increased production of NO in cerebral circulation was consistent with increase of cerebral blood volume. In conclusion, it seems reasonable to assume that increased cerebral blood volume may result from increased production of cerebral NO during endotoxemia.     

不同浓度异氟醚对大鼠大脑皮层乙酰胆碱含量的影响

目的观察吸入不同浓度异氟醚对大鼠大脑乙酰胆碱含量的影响,探讨异氟醚麻醉的中枢机制。方法 6只成年雄性SD大鼠,体重300-350 g,实验前2 d埋入导引管和微电极。实验前将微透析针插入大鼠大脑皮层,收集透析液,将微电极和HXD-1型多功能监测仪连接,同时监测脑电双频指数(BIS)、95％边缘频率(SEF);分别于吸入异氟醚前、吸入不同浓度异氟醚(0．6％、1．0％、 1．4％)30min后和停止吸入1h后收集透析液并同时记录BIS和SEF。结果随着异氟醚吸入浓度的增加,透析液中乙酰胆碱和胆碱含量逐渐降低(P<0．05或0．01)。停止吸入后1 h,乙酰胆碱和胆碱未恢复至基础值水平。BIS和SEF随着异氟醚浓度的增加,明显降低,停止吸入后1 h,BIS和SEF恢复到基础值水平。角膜反射消失时BIS、SEF分别为44．2±2．2、11．6±1．7。结论异氟醚全麻作用的中枢机制与中枢胆碱能系统有关。     

Effects of pneumoperitoneum and LPS-induced endotoxemia on cerebral perfusion pressure in pigs

Multitrauma patients commonly develop abdominal compartment syndrome, which is defined as the end result of sustained, uncorrected, intra-abdominal hypertension. We aimed to assess the effects of increased intra-abdominal pressure (IAP) upon intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in the presence or absence of lipopolysacharide (LPS)-induced endotoxemia using an experimental porcine model of pneumoperitoneum. Experimental procedures were approved by the Animal Care Review Committee of the National Veterinary Institute. Sixteen female pigs weighing 20 to 25 kg, aged 3 to 4 months were used. The animal model of increased IAP employed in our studies was produced with intraperitoneal administration of helium at 25 mm Hg under general anesthesia. After induction of pneumoperitoneum, 16 animals were randomly divided into 2 groups of 8 pigs each. One group received LPS intravenously (endotoxin group) and the second group received saline (control group). ICP, CPP, and hemodynamic variables were continuously monitored and recorded. A significant reduction of the cardiac output and concurrent increases in systemic vascular resistance and central venous pressure were observed in both groups after induction of pneumoperitoneum. ICP increased whereas CPP decreased significantly compared with baseline values in both groups after elevation of IAP. After LPS administration (endotoxin group), the cardiac output and mean arterial pressure decreased significantly. The CPP decreased further in the endotoxin group after LPS administration, whereas ICP remained unchanged. IAP increases produce significant increases in the ICP and decreases in the CPP in this animal model. LPS-induced endotoxemia further decreased CPP.     

Local cerebral glucose utilization during nitrous oxide and pentobarbital anesthesia in rats

Local cerebral glucose utilization was measured in rats during nitrous oxide and pentobarbital anesthesia, using the 2-[14C]-deoxyglucose method. During nitrous oxide anesthesia, 67%, marked heterogeneity of glucose utilization was observed. During pentobarbital anesthesia (30 mg/kg), glucose utilization decreased, the decrease being pronounced in the structures where glucose utilization was high during nitrous oxide anesthesia. During combined use of nitrous oxide and pentobarbital (30 mg/kg), with an electroencephalogram (EEG) consisting of 4-6 Hz wave super-imposed by 10-15 Hz wave, glucose utilization was higher in many brain structures, including the midbrain reticular formation, than that observed during pentobarbital (30 mg/kg) anesthesia alone. With pentobarbital, 125 mg/kg, the EEG became nearly flat and a dose-related decrease in glucose utilization was observed in the cerebral cortices and inferior colliculus but not observed in any other structures. During the combined use of nitrous oxide and pentobarbital (125 mg/kg), the EEG was nearly flat, and no statistically significant differences in glucose utilization were observed as compared with those during pentobarbital (125 mg/kg) anesthesia in any of the structures examined. The results suggest that nitrous oxide and pentobarbital affect local cerebral glucose metabolism differently and that nitrous oxide acts as cerebral metabolic stimulant in the presence of cortical function during pentobarbital anesthesia.     

Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. Conclusions: 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.