Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats

Aged rats are impaired on a spatial memory task for at least 24-48 h after isoflurane-nitrous oxide anesthesia. In this study, we tested how long the impairment lasts and investigated the role of nitrous oxide. Eighteen-month-old rats were randomized to anesthesia for 2 h with 1.2% isoflurane with or without 70% nitrous oxide or a control group (30% oxygen). Two weeks later, rats were tested daily for 14 days on a 12-arm radial maze. The number of correct choices to first error, total errors, and time to complete the maze were recorded. Rats anesthetized with 1.2% isoflurane with 70% nitrous oxide made fewer correct choices before first error (P < or = 0.05). Trends toward similar results were noted for error rate and time to complete the maze, but these did not achieve statistical significance. Post hoc analysis comparing all anesthetized rats to controls demonstrated that anesthetized rats made fewer correct choices to first error (P < or = 0.05) and took longer to complete the maze (P 相似文献   

Stress hormone changes in general anesthesia of long duration: isoflurane-nitrous oxide vs sevoflurane-nitrous oxide anesthesia

STUDY OBJECTIVE: There are few comparative studies of stress hormone changes during general anesthesia with long duration between isoflurane-nitrous oxide and sevoflurane-nitrous oxide anesthesia. We investigated perioperative changes of stress hormone in these two anesthetic methods with duration of more than 10 hours. DESIGN: Prospective study. SETTING: Operating room and high care unit of a university hospital. PATIENTS: Twenty patients with ASA physical status I or II for surgery for laryngeal or pharyngeal cancer with expected duration of more than 10 hours. INTERVENTIONS: Anesthesia was induced with midazolam, thiopental, and vecuronium and was maintained with sevoflurane (sevoflurane group) or isoflurane (isoflurane group) with nitrous oxide 4 L/min in oxygen 2 L/min. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, and anti-diuretic hormone (ADH); serum concentrations of glucagon and insulin; and blood glucose concentration were measured before inhalation of anesthetics, after 5 and 10 hours, and at 1, 6, and 12 hours after the end of inhalation. Epinephrine and norepinephrine concentrations increased continuously during and after surgery in the isoflurane group whereas it increased only after surgery in the sevoflurane group. Both concentrations were higher in the isoflurane group during anesthesia. Cortisol increased continuously whereas adrenocorticotropic hormone increased only during surgery. Anti-diuretic hormone increased with its peak during surgery and the isoflurane group had significantly higher values than the sevoflurane group. Glucose increased both during and after surgery, insulin increased only after surgery, and glucagon decreased during surgery in both groups. CONCLUSIONS: In inhalation anesthesia with the duration of more than 10 hours, isoflurane-nitrous oxide and sevoflurane-nitrous oxide had the same effects on stress hormone changes except for epinephrine, norepinephrine, and ADH. Epinephrine, norepinephrine, and ADH concentrations were higher in isoflurane-nitrous oxide anesthesia.     

Cardiovascular effects of isoflurane-nitrous oxide anesthesia in peripheral and abdominal surgical interventions

The cardiovascular actions of isoflurane-nitrous oxide anesthesia were studied in 20 patients (age rage 46-76 yr) undergoing laparatomy (group A = 13 patients) or peripheral vascular surgery (group B = 7 patients). Measurements were performed in the awake state, 20 min after induction of anesthesia and during surgical stimulation. Isoflurane produced small changes in heart rate but a significant reduction in mean arterial pressure which was due to a reduction in peripheral vascular resistance and myocardial contractility. During surgical stimulation arterial pressure rose above control values in group A but remained below control in group B. Cardiac index and stroke volume index both decreased after induction of anesthesia in group A and B. During surgical stimulation cardiac index increased in group A due to an increase in heart rate but remained below control in group B, while stroke volume index was reduced in both groups throughout the whole procedure. These results suggest, that contrary to the findings in human volunteers, isoflurane produces a significant cardiovascular depression in aged surgical patient.     

Regional coronary hemodynamics during isoflurane-nitrous oxide anesthesia in patients with ischemic heart disease

The effects of 1.5 MAC isoflurane-nitrous oxide anesthesia on central hemodynamics, regional coronary blood flow, myocardial oxygenation, and lactate balance were investigated in 13 patients with coronary artery disease. Mean arterial pressure was reduced 45% mainly because of systemic vasodilation. Great cardiac venous flow (GCVF) decreased, whereas total coronary sinus blood flow (CSF) was unchanged. Total coronary resistance and resistance in the area drained by the GCVF decreased as did myocardial oxygen extraction, demonstrating coronary vasodilation. The GCVF/CSF ratio did not decrease despite the reduction in resistance to left ventricular ejection. Seven patients had ECG and metabolic indications of myocardial ischemia (lactate extraction reduced from 22 +/- 5% to 7 +/- 3%, P less than 0.02 for the group). Changes in GCVF and oxygen consumption in the corresponding area correlated closely (r = 0.943). However, the regression line was shifted to the left and three patients, who became ischemic, had an increase in GCVF despite unchanged or decreased myocardial oxygen demand. It is concluded that isoflurane may cause coronary blood flow redistribution with regional myocardial ischemia in patients with coronary artery disease.     

The effects of isoflurane and isoflurane-nitrous oxide anesthesia on brainstem auditory evoked potentials in humans

Monitoring of brainstem auditory evoked potentials (BAEP) during neurological surgery can provide useful information. However, in order to interpret intraoperative BAEP changes, it is necessary to delineate the influence of anesthesia, including inhalation agents. In this study, we examined the influence of isoflurane and isoflurane-nitrous oxide anesthesia on BAEP in ten healthy volunteers during normothermic, normocapnic, and normotensive conditions. Isoflurane significantly increased the latencies of peaks III, IV, and V at all end-tidal concentrations studied (1.0%, 1.5%, and 2.0%). Addition of 50% nitrous oxide did not influence these findings. The increase in latencies with isoflurane anesthesia, however, was nonlinear and appeared to plateau after 1.5%. We suggest that during isoflurane anesthesia, an intraoperative increase in peak V latency beyond 1.0 msec is best explained by factors other than direct effects of isoflurane.     

昼夜行丙泊酚麻醉对大鼠空间学习记忆能力的影响

目的 利用Moms水迷宫(morris water maze,MWM),研究昼夜应用丙泊酚麻醉对于大鼠空间学习记忆能力的影响. 方法 雄性SD大鼠采用随机数字表法随机分为3组(每组8只):对照组(8:00～12:00给予10％脂肪乳0.5 mg·kg4·min4,23:00～3:00给予10％脂肪乳0.5 mg·kg-1·minq,C组)、明期给药组(8:00～12:00给予丙泊酚0.5 mg· kg-1·min-1,23:00～03:00给予10％脂肪乳0.5 mg· kg-1· min-1,L组)、暗期给药组(08:00～12:00给予10％脂肪乳0.5 mg· kg-1·min-1,23:00～03:00给予丙泊酚0.5 mg· kg4· min-1,D组).所有大鼠置于明暗周期下喂养(07:00～19:00为明期).C组动物于10％脂肪乳,L组和D组动物于丙泊酚停止输注后1、2、3d和4d分别进行MWM实验,记录各组大鼠的逃避潜伏期和穿环指数. 结果 第1天各组动物的逃避潜伏期差异无统计学意义(D0.05);第2天L组和D组用时分别为(56.3±1.3)s和(58.1±2.0)s,明显长于C组(29.5±0.9)s(P＜0.05),但两组之间差异无统计学意义(P＞0.05);第3天和第4天L组的逃避潜伏期分别为(38.6±0.8)s和(35.4±0.9)s,明显优于D组[(45.3±3.1)s和(41.1±1.3)s](P＜0.05),但两组较C组用时[(16.5±0.9)s和(16.1±0.8)s]均显著延长(P＜0.05).L组动物的穿环指数显著高于D组,但较C组明显减少(P＜0.05). 结论 丙泊酚麻醉尤其是暗期应用丙泊酚能对大鼠的空间学习记忆能力造成一定的损害.     

氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响

目的 探讨氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响.方法 健康清洁级雄性SD大鼠40只,随机分为4组(n=10):正常对照组(C组)腹腔注射等容量生理盐水;东莨菪碱组(S组)腹腔注射东莨菪碱0.8 mg/kg;东莨菪碱+氟马西尼组(SF组)腹腔注射东莨菪碱0.8 mg/kg和氟马西尼0.5 mg/kg;东莨菪碱+纳洛酮组(SN组)腹腔注射东莨菪碱0.8 mg/kg和纳洛酮2 mg/kg.1次/d,连续3 d.于第3天末次给药后30 min采用Y型迷宫进行学习记忆能力测试,记录达标训练次数和达标时间.处死后取脑,冰浴下分离海马,应用免疫组化法计数胆碱乙酰基转移酶(ChAT)免疫阳性神经元,采用RT-PCR法测定毒蕈碱受体M1亚型(mAChRM1)mRNA的表达.结果 与C组比较,S组、SF组和SN组达标时间延长,训练次数增加,ChAT阳性神经元计数减少,mAChRM1 mRNA表达下调(P<0.05).与S组比较,SF组和SN组达标时间缩短,训练次数减少,ChAT阳性神经元计数增多,mAChRM1 mRNA表达上调(P<0.05).结论 氟马西尼和纳洛酮可减轻东莨菪碱致大鼠认知功能障碍,其机制可能与改善大鼠中枢胆碱能神经系统功能有关.     

氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响

目的 探讨氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响.方法 健康清洁级雄性SD大鼠40只,随机分为4组(n=10):正常对照组(C组)腹腔注射等容量生理盐水;东莨菪碱组(S组)腹腔注射东莨菪碱0.8 mg/kg;东莨菪碱+氟马西尼组(SF组)腹腔注射东莨菪碱0.8 mg/kg和氟马西尼0.5 mg/kg;东莨菪碱+纳洛酮组(SN组)腹腔注射东莨菪碱0.8 mg/kg和纳洛酮2 mg/kg.1次/d,连续3 d.于第3天末次给药后30 min采用Y型迷宫进行学习记忆能力测试,记录达标训练次数和达标时间.处死后取脑,冰浴下分离海马,应用免疫组化法计数胆碱乙酰基转移酶(ChAT)免疫阳性神经元,采用RT-PCR法测定毒蕈碱受体M1亚型(mAChRM1)mRNA的表达.结果 与C组比较,S组、SF组和SN组达标时间延长,训练次数增加,ChAT阳性神经元计数减少,mAChRM1 mRNA表达下调(P<0.05).与S组比较,SF组和SN组达标时间缩短,训练次数减少,ChAT阳性神经元计数增多,mAChRM1 mRNA表达上调(P<0.05).结论 氟马西尼和纳洛酮可减轻东莨菪碱致大鼠认知功能障碍,其机制可能与改善大鼠中枢胆碱能神经系统功能有关.     

氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响

目的 探讨氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响.方法 健康清洁级雄性SD大鼠40只,随机分为4组(n=10):正常对照组(C组)腹腔注射等容量生理盐水;东莨菪碱组(S组)腹腔注射东莨菪碱0.8 mg/kg;东莨菪碱+氟马西尼组(SF组)腹腔注射东莨菪碱0.8 mg/kg和氟马西尼0.5 mg/kg;东莨菪碱+纳洛酮组(SN组)腹腔注射东莨菪碱0.8 mg/kg和纳洛酮2 mg/kg.1次/d,连续3 d.于第3天末次给药后30 min采用Y型迷宫进行学习记忆能力测试,记录达标训练次数和达标时间.处死后取脑,冰浴下分离海马,应用免疫组化法计数胆碱乙酰基转移酶(ChAT)免疫阳性神经元,采用RT-PCR法测定毒蕈碱受体M1亚型(mAChRM1)mRNA的表达.结果 与C组比较,S组、SF组和SN组达标时间延长,训练次数增加,ChAT阳性神经元计数减少,mAChRM1 mRNA表达下调(P<0.05).与S组比较,SF组和SN组达标时间缩短,训练次数减少,ChAT阳性神经元计数增多,mAChRM1 mRNA表达上调(P<0.05).结论 氟马西尼和纳洛酮可减轻东莨菪碱致大鼠认知功能障碍,其机制可能与改善大鼠中枢胆碱能神经系统功能有关.     

Hemorrhage during isoflurane-nitrous oxide anesthesia: effects of endothelin-A or angiotensin II receptor blockade or both

BACKGROUND: The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia. METHODS: Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour. RESULTS: Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol. CONCLUSIONS: ETAB impairs long-term hemodynamic regulation after hemorrhage and retransfusion during anesthesia despite an activation of vasoconstrictive hormones. This suggests that endothelins have a role in long-term cardiovascular regulation. AT1B impairs both short- and long-term blood pressure regulation during anesthesia and after hemorrhage.     

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients

We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.     

Randomized controlled trial of total intravenous anesthesia with propofol versus inhalation anesthesia with isoflurane-nitrous oxide: postoperative nausea with vomiting and economic analysis

BACKGROUND: To assess the incidence of postoperative nausea and vomiting after total intravenous anesthesia (TIVA) with propofol versus inhalational anesthesia with isoflurane-nitrous oxide, the authors performed a randomized trial in 2,010 unselected surgical patients in a Dutch academic institution. An economic evaluation was also performed. METHODS: Elective inpatients (1,447) and outpatients (563) were randomly assigned to inhalational anesthesia with isoflurane-nitrous oxide or TIVA with propofol-air. Cumulative incidence of postoperative nausea and vomiting was recorded for 72 h by blinded observers. Cost data of anesthetics, antiemetics, disposables, and equipment were collected. Cost differences caused by duration of postanesthesia care unit stay and hospitalization were analyzed. RESULTS: Total intravenous anesthesia reduced the absolute risk of postoperative nausea and vomiting up to 72 h by 15% among inpatients (from 61% to 46%, P < 0.001) and by 18% among outpatients (from 46% to 28%, P < 0.001). This effect was most pronounced in the early postoperative period. The cost of anesthesia was more than three times greater for propofol TIVA. Median duration of stay in the postanesthesia care unit was 135 min after isoflurane versus 115 min after TIVA for inpatients (P < 0.001) and 160 min after isoflurane versus 150 min after TIVA for outpatients (P = 0.039). Duration of hospitalization was equal in both arms. CONCLUSION: Propofol TIVA results in a clinically relevant reduction of postoperative nausea and vomiting compared with isoflurane-nitrous oxide anesthesia (number needed to treat = 6). Both anesthetic techniques were otherwise similar. Anesthesia costs were more than three times greater for propofol TIVA, without economic gains from shorter stay in the postanesthesia care unit     

Changes in prefrontal neuronal activity after learning to perform a spatial working memory task

The prefrontal cortex is considered essential for learning to perform cognitive tasks though little is known about how the representation of stimulus properties is altered by learning. To address this issue, we recorded neuronal activity in monkeys before and after training on a task that required visual working memory. After the subjects learned to perform the task, we observed activation of more prefrontal neurons and increased activity during working memory maintenance. The working memory-related increase in firing rate was due mostly to regular-spiking putative pyramidal neurons. Unexpectedly, the selectivity of neurons for stimulus properties and the ability of neurons to discriminate between stimuli decreased as the information about stimulus properties was apparently present in neural firing prior to training and neuronal selectivity degraded after training in the task. The effect was robust and could not be accounted for by differences in sampling sites, selection of neurons, level of performance, or merely the elapse of time. The results indicate that, in contrast to the effects of perceptual learning, mastery of a cognitive task degrades the apparent stimulus selectivity as neurons represent more abstract information related to the task. This effect is countered by the recruitment of more neurons after training.     

Interaction between anesthesia,gender, and functional outcome task following diffuse traumatic brain injury in rats

A number of experimental and clinical studies have demonstrated that functional outcome following traumatic brain injury differs between males and females. Some studies report that females have a better outcome than males following trauma while others report the opposite. In experimental studies, some of the contradictory results may be due to the different experimental conditions, including type of anesthesia and the outcome measures employed. In the present study we have used three different anesthetic protocols and four different outcome measures to determine how these parameters interact and affect functional outcome following traumatic brain injury in male and female rats. Diffuse traumatic brain injury was induced in adult male and female animals using the impact-acceleration brain injury model. Mortality in female animals was no different than males when using halothane anesthesia, slightly better than males when using isoflurane anesthesia, but significantly worse than males under pentobarbital anesthesia. Female animals always performed better than males on rotarod tests of motor outcome, with this effect being unrelated to anesthetic effects. Conversely, in cognitive tests using the Barnes Maze, only isoflurane-anesthetized females performed better than their male counterparts. Similarly, in an open field activity task, females always performed better than males after trauma, with isoflurane-anesthetized females also performing significantly better than the halothane-anesthetized female group after injury. Our results suggest that female animals do better than males after diffuse traumatic brain injury, although this observation is dependent upon the type of anesthesia and the functional task employed. Isoflurane is particularly protective in females, pentobarbital is deleterious to female outcome, while halothane anesthesia has the least influence on gender-related outcome.     

Roles of attention, memory, and motor preparation in modulating human brain activity in a spatial working memory task

Neuronal activity of the human brain was studied with magnetoencephalography (MEG) in a spatial working memory task similar to those commonly used with nonhuman primates. The subject was required to remember target positions for 3 s and make a same-different judgement with a finger lift comparing the position of the probed target with the probe or to execute a memory-guided saccade to the probed target. In this type of task single-unit studies have shown attention- and memory-related activities independent of movement type during the retention interval in a large number of cortical areas of the primates, including the parietal and prefrontal areas. Consistent with these results, there were strong stimulus-driven transient and sustained responses and modulations of oscillatory activity during the retention period. Although we did not determine the source locations, coarse estimates of the currents responsible for the MEG signals showed activity over a wide area of the cortex, most prominently over the Rolandic, parietal and occipital areas, but also over the frontal area. Some of the activities in these cortical areas reflect processes that may be identified with attention and memory, while others were related to preparation of the overt movements.      

Effects of isoflurane-nitrous oxide anaesthesia on insulin secretion in female patients

In vitro studies suggest that volatile anaesthetic agents may directly inhibit insulin secretion. It is unclear if supplementation of anaesthesia with isoflurane impairs insulin secretion. We performed a 5- g i.v. glucose tolerance test in 21 patients before and during anaesthesia which was maintained with either 1 or 2 MAC of isoflurane in nitrous oxide, or no volatile agent. The study was carried out before surgery to avoid the influence of hormonal responses to trauma. A significant glycaemic response occurred during both i.v. glucose tolerance tests in all three groups of patients. Serum insulin concentrations were measured and the acute increase in insulin concentration at 3 min and area under the curve for 15 min were calculated. Both variables decreased significantly in all three groups during the tests performed under anaesthesia compared with tests carried out before anaesthesia.