Extracellular Concentrations of Taurine,Glutamate, and Aspartate in the Cerebral Cortex of Rats at the Asymptomatic Stage of Thioacetamide-Induced Hepatic Failure: Modulation by Ketamine Anesthesia

Subclinical hepatic encephalopathy (SHE) was produced in rats by two intraperitoneal injections of TAA at 24 h intervals and the animals were examined 21 days later. Concentrations of the neuroactive amino acids taurine (Tau), glutamate (Glu) and aspartate (Asp), were measured in the cerebral cortical microdialysates of thioacetamide (TAA)-treated and untreated control rats. During microdialysis some animals were awake while others were anesthetized with ketamine plus xylazine. There was no difference in the water content of cerebral cortical slices isolated from control and SHE rats, indicating a recovery from cerebral cortical edema that accompanies the acute, clinical phase of hepatic encephalopathy in this model. When microdialysis was carried out in awake rats, dialysate concentrations of all the three amino acids were 30% to 50% higher in SHE rats than in control rats. Ketamine anesthesia caused a 2.2% increase of water content of cerebral cortical slices and increased Asp, Glu, and Tau concentration in microdialysates of control rats. In SHE rats, ketamine anesthesia produced a similar degree of cerebral edema, however, it did not alter Asp and Glu concentrations in the microdialysates. These data may reflect on one hand a neuropathological process of excitotoxic neuronal damage related to increased Glu and Asp, on the other hand neuroprotection from neuronal swelling indicated by Tau redistribution in the cerebral cortex. The reduction of the effects of SHE on Glu and Asp content in ketamine-anesthesized rats is likely to be due to interference of ketamine with the NMDA receptor-mediated component of the SHE-evoked excitatory neurotransmitter efflux and/or reuptake of the two amino acids. By contrast, the SHE-related increase of Tau content was not affected by ketamine anesthesia, indicating that the mechanism(s) underlying SHE-evoked accumulation of Tau must be different from the mechanism causing release of excitatory amino acids. The results with ketamine advocate caution when using this anesthetic in studies employing the cerebral microdialysis technique for measurement of extracellular amino acids.     

Acepromazine-ketamine anesthesia in the rhesus monkey (Macaca mulatta).

Six adult male rhesus monkeys (Macaca mulatta) were anesthetized using a combination of acepromazine maleate and ketamine hydrochloride administered by intramuscular injection. This combination produced a smooth induction to anesthesia requiring less than 5 minutes. The average duration of anesthesia was slightly less than 1 hour and was safely prolonged with additional doses of ketamine. The depth of anesthesia was sufficient for minor surgical procedures and for precise radiological studies. No deleterious side effects were noted, and animals recovered completely in a short time.     

山羊单纯与复合全身麻醉效果的比较

目的对比山羊单纯麻醉与复合麻醉的效果,探讨一种安全高效便捷的山羊麻醉方法。方法选取山羊30只,随机分为A、B、C三组,A组给予单纯戊巴比妥钠麻醉,B组给予单纯氯胺酮麻醉,C组给予地西泮、戊巴比妥钠和氯胺酮复合麻醉,记录三种麻醉方法的起效时间、麻醉维持时间、麻醉药物用量及麻醉死亡率。结果地西泮、戊巴比妥钠和氯胺酮复合麻醉,起效快、麻醉维持时间长、动物死亡率低、麻醉效果好。结论安定、戊巴比妥钠和氯胺酮复合麻醉优于单纯麻醉,是一种高效、便捷、安全山羊全身麻醉方法。     

小型猪生物可降解支架置入术中不同麻醉方法的研究

目的比较两种不同麻醉方法对小型猪的麻醉效果。方法将12头小型猪随机分成两组,每组6头,一组是戊巴比妥钠复合氯胺酮静脉麻醉（Ⅰ组）,另一组是丙泊酚复合氯胺酮静脉麻醉（Ⅱ组）。麻醉后对动物实施心脏生物可降解支架置入术,观察动物麻醉起效时间、苏醒时间、麻醉效果、呼吸频率（RR）、心率（HR）、血氧饱和度（SpO2）及术后苏醒情况。结果两种方法麻醉后,动物分别在7.6±2.4 min（Ⅰ组）、2.4±1.4 min（Ⅱ组）进入麻醉状态（P〈0.05）。术后苏醒时间分别为30.8±8.8 min（Ⅰ组）、16.5±2.8min（Ⅱ组）（P〈0.05）,Ⅱ组动物比Ⅰ组动物苏醒平稳（P〈0.05）。两组心率及呼吸频率变化无明显差别,而氧饱和度在第10 min（Ⅰ组87%,Ⅱ组92%）和30 min（Ⅰ组94%,Ⅱ组89%）由于追加麻醉药后,两组值差异较大,但很快恢复正常。Ⅱ组麻醉效果较Ⅰ组麻醉效果好。结论两种麻醉方法均能达到良好的麻醉效果,丙泊酚复合氯胺酮麻醉较戊巴比妥钠复合氯胺酮麻醉的效果强且术后苏醒快,是一种比较理想的麻醉方法。     

Electrocardiographic changes in rats undergoing thoracic surgery under combined parenteral anesthesia

To compare two protocols of combined parenteral general anesthesia, the authors analyzed electrocardiographic changes in anesthetized rats undergoing left pneumonectomy. One group of rats was anesthetized with a combination of medetomidine and ketamine (group 1, n = 10), and the other was injected with diazepam and ketamine (group 2, n = 10). Investigators obtained two electrocardiograms from each rat, one before surgery (5 min after anesthesia) and one after surgery (60 min after anesthesia). Anesthetic induction was quick for all rats, though four rats in group 2 died before surgery. Mean cardiac frequency and R-wave amplitude were significantly lower in rats in group 1 than in rats in group 2. Rats in group 1 received injections of atipamezole about 60 min after surgery, which reversed the effects of medetomidine; these rats regained voluntary respiratory movement more quickly than did rats in group 2. Two additional rats in group 2 died during postsurgical recovery. These results suggest that for thoracic surgery in rats, medetomidine-ketamine is an appropriate anesthetic combination, may be safer than diazepam-ketamine and yields a shorter recovery time.     

A comparison of ketamine/xylazine and ketamine/xylazine/acepromazine anesthesia in the rabbit

Parenteral anesthetic combinations such as ketamine and xylazine have become the agents of choice for anesthesia in the rabbit, because they are effective, easily administered and inexpensive. A number of recent reports have recommended including acepromazine in this combination, but a critical evaluation of this combination in the rabbit has not been reported. Five adult New Zealand white rabbits were anesthetized intramuscularly with ketamine (35 mg/kg) and xylazine (5 mg/kg) with or without acepromazine (0.75 mg/kg). The study was conducted in a double blind fashion, where each rabbit was administered both combinations at a minimum of 7 day intervals. Physiologic parameters were evaluated including heart rate, respiratory rate, central arterial blood pressure, pedal, palpebral and postural reflex activity. The duration of general anesthesia, estimated by the time elapsed between the loss and return of the palpebral reflex, was greater (means = 99 +/- 20 minutes) when acepromazine was employed in the combination compared to (means = 77 +/- 5 minutes) when ketamine/xylazine were used alone. Mean central arterial blood pressure reached a lower level when acepromazine was utilized (means = 46 +/- 8 mm/Hg) than when it was not (means = 57 +/- 12 mm/Hg.). The addition of acepromazine in a ketamine/xylazine combination resulted in a 28% longer period of anesthesia, a 19% lower mean central arterial blood pressure and a 32% longer recovery of postural reflexes. The ketamine/xylazine/acepromazine combination is a useful regimen for normovolemic animals when anesthetic duration greater than that produced by ketamine/xylazine alone is required.     

Ketamine/xylazine anesthesia for radiologic imaging of neurologically impaired rats: dose response, respiratory depression, and management of complications

In vivo imaging of rats represents an important tool for outcome evaluation in research on stroke, brain trauma, and other neurologic diseases. Since sedation of animals is necessary to avoid artifacts, a mixture of ketamine and xylazine is frequently used for anesthesia. We assessed the suitable dosage of narcotics and its correlation to severe respiratory adverse events in 269 cases of ketamine/xylazine anesthesia in male Wistar rats for performance of magnetic resonance imaging after middle cerebral artery occlusion (MCAO) or sham surgery. Anesthesia depth was not measured. Anesthesia was efficacious in avoiding movement artifacts during imaging. Necessary dosage was lower if rodents were subjected to MCAO instead of sham surgery, if body weight was below baseline, and if time since surgery was short. If anesthesia was induced during the first 2 days after surgery in animals with body weight loss, necessary dose rates were 27% below doses required for rats more than 10 days post-surgery with body weight above baseline (91.4/8.3 versus 125.1/11.3 mg of ketamine/xylazine/kg). A dose adaptation scale for the prediction of necessary dose rates was developed. Apnea developed in 3.3% of all animals. Use of ketamine/xylazine anesthesia for imaging procedures is feasible and safe, though it is associated with a small risk of respiratory arrest. In case of apnea, inspiration can be provoked by a puff of air into the rat's pelt. If unsuccessful, endotracheal intubation and mechanical ventilation are needed until spontaneous breathing is restored or xylazine effects are antagonized.     

Anesthesia in the rabbit using a combination of ketamine and promazine

An anesthetic combination of ketamine and promazine (75mg/kg by ketamine content) was tested in 15 male and 15 female adult New Zealand white rabbits. The mean induction time was 9 minutes for both the male and female. Mean duration for anesthesia was 61 minutes for the male and 49 minutes for the female. The mean recovery time was 22 minutes for the male and 33 minutes for the female. The drug combination provided effective anesthesia for a period of 50--60 minutes after a single intramuscular injection.     

Comparative immobilization of wild felids in Thailand

We immobilized individuals of four free-ranging felid species, leopard cat (Prionailurus bengalensis), clouded leopard (Neofelis nebulosa), Asiatic golden cat (Catopuma temminckii), and marbled cat (Pardofelis marmorata) with ketamine hydrochloride and xylazine hydrochloride (KH-XH) and with tiletamine hydrochloride and zolazepam hydrochloride (TH-ZH) between March 1998 and July 2002. Mean (+/-SD) dose of KH and XH was 26.51+/-5.71 mg/kg and 1.89+/-0.43 mg/kg, respectively (n=25), and mean dose of TH-ZH was 11.61+/-3.39 mg/kg (n=28). Dose was significantly correlated with induction time (P<0.001) and duration of anesthesia (P<0.05), but not with recovery time. There were significant differences between the drug combinations in time to induction (P<0.03) and time to anesthesia (P<0.01); recovery times were not significantly different. We conclude that immobilization of these felids with TH-ZH and KH-XH is effective and safe, but TH-ZH is preferred because of the smaller volume of drug necessary for sedation, faster time to induction, and absence of prolonged muscle rigidity during anesthesia.     

Reversal of ketamine/xylazine anesthesia in the rabbit with yohimbine

Ketamine and xylazine used in combination have been shown to be effective, easily administered, cost efficient agents for surgical anesthesia in the rabbit. The effect of xylazine on the central nervous system has been shown to be mediated through alpha-2 adrenergic receptors. Yohimbine, an alpha-2 adrenergic antagonist has been shown to reverse xylazine induced depression and partially antagonize ketamine in other species. We evaluated the antagonistic effect of yohimbine on ketamine/xylazine anesthesia in the rabbit. Six New Zealand White rabbits were anesthetized with intramuscular ketamine (50 mg/kg) and xylazine (10 mg/kg) to establish baseline parameters including respiratory rate, heart rate, and palpebral, pedal and postural reflex activity. Fourteen days later each rabbit was subjected to the same anesthetic regimen followed 30 minutes later by the intravenous administration of yohimbine (0.2 mg/kg). The duration of anesthesia estimated by the time elapsed between the loss and return of the palpebral reflex was reduced in the yohimbine treated trial (means = 29.7 +/- 1.9 minutes) compared to the control trial (means = 67.0 +/- 13.5 minutes). The palpebral reflex returned within 5 minutes following yohimbine treatment. Our results indicated that yohimbine is an effective antagonist of ketamine/xylazine anesthesia in the rabbit. Yohimbine decreases anesthetic duration after intravenous administration and also may aid in the control of undesirable anesthetic effects and overdosage.     

氯胺酮复合咪达唑仑全麻在无水乙醇治疗先天性周围血管畸形中的效果评价

目的:观察氯胺酮复合咪达唑仑在无水乙醇治疗儿童先天性周围血管畸形的应用效果。方法:选择择期全麻下行无水乙醇治疗周围血管畸形儿童50例,随机分为两组:氯胺酮复合咪达唑仑组(M组)和丙泊酚持续输注组(P组),M组以咪达唑仑和氯胺酮基础下全麻,P组采用芬太尼镇痛基础下丙泊酚持续静注全麻,观察并记录入室(T_0)、麻醉诱导后5 min(T_1)、手术开始后30、60、90 min(分别为T_2、T_3、T_4)、拔管后5 min(T_5)的MAP与HR,监测脑电双频指数(bispectral index,BIS)并记录BIS40次数、平均注射无水乙醇量、术中输液量、苏醒时间及苏醒后5 min视觉模拟评分(Visual analog scales,VAS)、Ramsay镇静评分结果。结果:(1)与M组相比,P组MAP(T_2～T_54个时间点)、HR(T_1～T_55个时间点)和BIS值(T_3和T_42个时间点)均显著降低,差异有统计学意义(P0.05);三个指标其余时间点两组患儿相比,差异均无统计学意义(P0.05);(2)与M组患儿相比,P组BIS值40的患儿例数以及应用阿托品和麻黄碱例数均显著增加,差异具有统计学差异(P0.05);两组患儿平均无水乙醇注射量比较显著差异无统计学意义(P0.05);(3)与M组相比,P组患儿全麻苏醒拔管后5 min VAS评分显著降低,Ramsay评分显著升高(P0.05);两组患儿不良事件发生率均无统计学差异(P0.05)。结论:氯胺酮复合咪达唑仑下全麻应用于无水乙醇注射治疗儿童周围血管畸形,能维持术中血流动力学平稳,且缩短苏醒时间。     

Nitric oxide induced by ketamine/xylazine anesthesia maintains hepatic blood flow during hypothermia.

Among the anesthetics influencing the nitric oxide (NO) pathway, ketamine is widely reported in the literature. We researched the variations in blood physiological parameters following ketamine/xylazine- or pentobarbital-induced anesthesia, with particular emphasis on plasmatic NO levels and oxidative stress-related factors. The effects of ketamine on hepatic blood flow during deep hypothermia were also examined. Adult male Sprague-Dawley rats were anesthetized intraperitoneally with ketamine/xylazine or with sodium pentobarbital. Animals underwent serial blood extraction to analyze acid-base balance and lactate levels in blood, as well as NO, MDA, SH groups, and AST levels in plasma samples. We demonstrated that ketamine leads to increased plasmatic NO levels, induces metabolic acidosis, and causes oxidative damage, though without reaching hepatic toxicity. When experimental hypothermia was induced, ketamine affected hepatic blood flow. Based on these results, we suggest that studies on physiological processes involving NO should exercise caution if anesthesia is induced by ketamine.     

Comparison between the effects of pentobarbital or ketamine/nitrous oxide anesthesia on metabolic and endothelial components of coronary reactive hyperemia

Barbiturates induce reduction of myocardial contractility and metabolism, whereas ketamine exerts a sympathomimetic effect that can mask its direct depressant effect on contractility. However, it is unclear whether barbiturates, which interfere with the cytochrome P-450 pathway, or ketamine, which inhibits nitric oxide synthesis, also alter the responsiveness of the coronary vessels to vasodilator stimuli. We hypothesized that the parameters of coronary reactive hyperemia (CRH), which reflect both the degree of myocardial metabolism and vascular reactivity, could be modified by the type of anesthesia used. In two groups of goats, anesthesia was induced either using ketamine plus nitrous oxide or pentobarbital alone. To record coronary flow an electromagnetic flow-probe was placed around the left circumflex coronary artery. In the ketamine group (n = 14) and in the pentobarbital group (n = 16) CRH was studied using the indices of myocardial metabolism and vascular dilator responsiveness. In the pentobarbital group all of the indices of myocardial metabolism were lower than in the ketamine group (i.e. the excess to debt flow ratio was 2.3+/-0.8 vs. 4.6+/-2.4; p< 0.001). Yet, some indices of vascular responsiveness (time derivative of coronary flow and the peak to basal flow ratio) were not different in the two groups. Moreover, the duration of the reactive hyperemia was shorter in the ketamine than in the pentobarbital group (118+/-47 vs. 153+/-45 s, p<0.05). It is suggested that pentobarbital decreases the indices of CRH related to metabolic activity, whereas ketamine reduces the duration of the hyperemic response, which suggests an impairment of endothelial function.     

The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

不同剂量氯胺酮复合顺式阿曲库铵预注对肌松效应的影响

目的比较顺式阿曲库铵预注、不同剂量氯胺酮复合顺式阿曲库铵预注对顺式阿曲库铵起效时间、血流动力学的影响。方法选择全麻下行择期手术的患者120例随机分成4组,即Ⅰ(生理盐水0.5ml)组、Ⅱ(顺式阿曲库铵0.01mg/kg)组、Ⅲ(顺式阿曲库铵0.01mg/kg预注复合氯胺酮0.5mg/kg)组、Ⅳ(顺式阿曲库铵0.01mg/kg预注复合氯胺酮1mg/kg)组,预注、预处理3min后,Ⅰ组静注插管剂量顺式阿曲库铵0.15mg/kg,Ⅱ、Ⅲ、Ⅳ组静注剩余插管剂量顺式阿曲库铵0.14mg/kg。使用四个成串刺激(TOF),待T1达最大抑制程度时行气管插管,记录肌松起效时间,同时观察HR、BP的变化。结果Ⅱ、Ⅲ、Ⅳ组肌松起效时间明显短于Ⅰ组(P0.05),且Ⅲ、Ⅳ组起效时间较Ⅱ组短(P0.05),但Ⅲ、Ⅳ组起效时间比较无统计学意义(P0.05);各组麻醉诱导期间均无明显心血管不良反应。结论氯胺酮0.5mg/kg复合顺式阿曲库铵0.01mg/kg、氯胺酮1mg/kg复合顺式阿曲库铵0.01mg/kg均能进一步缩短肌松起效时间,且无明显心血管不良反应。     

The effects of ketamine anesthesia on glucose clearance in African green monkeys

Ketamine hydrochloride's effect on glucose clearance-insulin secretion during intravenous glucose tolerance testing was studied in five African green monkeys. Animals were tested with ketamine anesthesia and then had indwelling cannulas implanted and were retested both in the presence and absence of ketamine anesthesia. Serum glucose and insulin concentrations were determined. There were no significant differences in the glucose clearance rate (K value), basal glucose and insulin concentrations, maximum insulin concentration, and area under the insulin response curve, among the three different conditions.     

Anesthesia of boma-captured Lichtenstein's hartebeest (Sigmoceros lichtensteinii) with a combination of thiafentanil,medetomidine, and ketamine

A dose range was determined for anesthesia of recently boma-captured Lichtenstein's hartebeest (Sigmoceros lichtensteinii) (n = 13) with the synthetic opiate thiafentanil (THIA) (formerly called A3080) combined with medetomidine (MED) and ketamine (KET) in the Kasungu National Park, Malawi on 4 to 5 September 1999. The dose range of 11-29 micrograms/kg THIA (mean +/- SD = 21 +/- 4 micrograms/kg) combined with 5-10 mg/kg MED (8 +/- 1 micrograms/kg) plus 0.7-1.4 mg/kg KET (1.1 +/- 0.2 mg/kg) was found to be safe and effective for the field conditions associated with this study. The anesthesia produced by this drug combination was very predictable and characterized by a short induction time (3:34 +/- 1:20 min:sec), good muscle relaxation, and acceptable physiologic parameters for anesthesia periods ranging from 22:30-35:00 min:sec (31:14 +/- 2:50). Within the range of doses used in this study, times to onset of initial effects and recumbency were not dependent on THAI, MED, or KET doses. Anesthesia was rapidly and completely reversed by intravenous injections of naltrexone at 30 times the THAI dosage (0.69 +/- 0.19 mg/kg) and atipamezole at about four times the MED dosage (38 +/- 14 micrograms/kg). There was no residual effect from ketamine noted following reversal of THIA and MED and no mortality or morbidity was associated with this anesthetic regimen.     

Role of excitatory amino acids in hypoxic preconditioning.

We examined the effects of the extrinsic ionotropic NMDA receptor agonist (aspartate) and antagonist (ketamine) on the hypoxic preconditioning of mice and the concentration changes of intrinsic excitatory amino acids (EAAs), aspartate and glutamate, in the whole brain and different brain regions during preconditioning by an HPLC method. Our results showed that aspartate and ketamine significantly prolonged and shortened the standard tolerance time of mice during preconditioning and survival time in hypobaric chambers, respectively. After the 1st exposure, EAA concentrations in the whole brain and brain regions were increased. After run 4, they were decreased or maintained. It is suggested that the activation and suppression of ionotropic NMDA receptors is harmful and beneficial to hypoxic preconditioning, respectively. Degradation and/or inactivation of EAAs might be beneficial to the tolerance of mice to hypoxia.     

Glutamate Release in Experimental Ischaemia of the Retina: An Approach Using Microdialysis

A rabbit eye model of neural ischaemia is described that uses an increased pressure in the anterior eye chamber to block the capillary supply to the retina. A microdialysis probe placed very close to the retinal surface was used to monitor release of amino acids during ischaemia. A large (two- to threefold) increase in the release of glutamate and O-phosphoserine (twofold), but not of six other amino acids monitored, occurred during initial ischaemia. During reperfusion after release of intraocular pressure, much larger (five- to 10-fold) increases in the release of these amino acids were observed. Parallel ischaemic retinal tissue damage was observed. This damage was prevented by ketamine applied locally via a superfusion needle, suggesting that glutamate released during ischaemia, and particularly during reperfusion, was responsible for cell death.     

Breathing pattern and CO2 response in newborn rats before and during anesthesia

We have studied the breathing pattern (minute ventilation VE, tidal volume VT, and respiratory rate f) in newborn rats before and during barbiturate (20-30 mg/kg ip) or ketamine anesthesia (40-80 mg/kg ip). Animals were intact and prone in a flow plethysmograph in thermoneutral conditions. Before anesthesia, CO2 breathing (5 min in 5% and 5 min in 10% CO2 in O2) resulted in a substantial increase in VE (169 and 208%, respectively), which was maintained throughout the entire CO2 breathing period. This indicates that, despite the extremely large VE per kilogram at rest, in these small animals there is still a large reserve for a sustained increase in VE. During barbiturate, the resting VE dropped to 45% of control, due to a reduction in VT (83%) and f (59%). This latter result was due to a prolongation of the expiratory time (214%) with no significant changes in inspiratory time. CO2 response was also much depressed, to approximately 63% of the control. The late portion of the expiratory flow-volume curves, the slope of which represents the expiratory time constant of the system, was similar before and during anesthesia in approximately 50% of the animals, whereas it increased during anesthesia in the remaining animals. Although compliance of the respiratory system was generally unaltered, the increased impedance during anesthesia probably reflected an increased resistance. Qualitatively similar results were obtained during ketamine anesthesia. Therefore, as observed in adult mammals, anesthesia in newborn rats has a marked depressant effect on resting breathing pattern and CO2 response, occasionally accompanied by an increase in the expiratory impedance of the respiratory system.