水合氯醛、乌拉坦及其1:1 混合液在SD 大鼠麻醉中的效果比较及应用

目的:比较水合氯醛、乌拉坦及其1:1混合液在SD大鼠麻醉中的效果并进一步在大鼠模型制备的麻醉中检验其效果。方法:分别采用不同剂量的水合氯醛和乌拉坦及其1:1混合液进行麻醉实验,比较其麻醉起效时间、维持时间和死亡率,并将相同剂量的1:1混合液应用于SD大鼠模型制作时的麻醉中,比较其与非模型组之间的差异。结果:水合氯醛和乌拉坦混合液麻醉大鼠的起效时间2.5±1.5分钟,与单用水合氯醛无差异(P>0.05),比单用乌拉坦起效时间短(P<0.05);维持时间107.4±4.1分钟,比单用水合氯醛、乌拉坦长(P<0.01);麻醉死亡率比单用水合氯醛低,总死亡率比单用水合氯醛、乌拉坦低。模型组大鼠的麻醉起效时间2.9±1.6分钟,维持时间108.9±4.4分钟,零麻醉死亡率,总死亡率为2.5%;与1:1混合液非模型组的麻醉效果没有明显差异。结论:水合氯醛+乌拉坦1:1混合液麻醉效果好、起效快、死亡率极低,适合用于2小时左右的SD大鼠手术或模型制作。     

Evaluation of maternal and embryotoxic effects following the treatment of chloral hydrate in Drosophila melanogaster

Chloral hydrate (CH) is commonly used as a sedative and a hypnotic in pediatric medicine. In this study, the effects of CH on various developmental stages of Drosophila melanogaster were investigated. Different concentrations of CH (0.1; 0.3; 0.5 and 1 mg/mL) were used during development of the flies. Maternal toxicity due to increasing the concentration of CH was observed as a large number of adult flies died. When the F₁ progeny of the control and application groups were compared, CH was found to extend the process of metamorphosis and to decrease the total number of offspring. The embryotoxic effects on the offspring and an increase in the number of malformed offspring was identified as depending on feeding. It was found that the difference between the groups was significantly important (p < 0.05).     

Cardiorespiratory effects of diazepam-ketamine, xylazine-ketamine and thiopentone anesthesia in male Wistar rats--a comparative analysis

Several anesthetics are known to cause respiratory and cardiovascular depression in humans and animals; but, these diverse effects have not been extensively investigated in laboratory rodents. The objective of this study is to choose a suitable anesthetic combination for use in surgical models eg. coronary artery ligation in rats. Male Wistar rats were anesthetized with three different drugs viz. diazepam-ketamine (DK) (2.5 mg/Kg, intraperitoneally (i.p); 50 mg/Kg, i.p), xylazine-ketamine (XK) (5 mg/Kg i.p; 50 mg/Kg i.p) and thiopentone (T) (40 mg/Kg i.p) and the respiratory and cardiovascular functions were assessed after coronary artery ligation. Heart rate (HR), mean arterial pressure (MAP), partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), oxygen saturation percentage (O2 sat (%)), arterial blood pH and rectal body temperature were studied in detail. During the anesthetic regime, HR was lower till 60 min in XK and T ligated group (333 +/- 6; 304 +/- 8 beats/min) and it was near normalcy in the case of DK ligated group (394 +/- 6 beats/min). Significant respiratory depression was particularly reflected in the T ligated group with an increase in PaCO2 at 30 min (40.32 +/- 2.64 mmHg), which decreased to 38.2 +/- 2.23 mmHg at 60 min. Throughout the investigation, DK showed the least overall effects compared to XK and T on respiratory functions. Thus, DK could be considered to be a suitable anesthetic for use in a surgical model such as coronary artery ligation in albino rats.     

Immobilization with a single dose of ketamine hydrochloride and a combination of xylazine hydrochloride-ketamine hydrochloride and antagonism by yohimbine hydrochloride in the Japanese monkey (Macaca fuscata)

Forty-nine free-ranging Japanese monkeys (Macaca fuscata) were immobilized with 4.3–15.6 mg/kg (mean±S.D.=10.0±2.5 mg/kg) of ketamine hydrochloride (HCl), and 27 Japanese monkeys kept in enclosures were immobilized with a combination of 0.8–1.4 mg/kg (1.0±0.2 mg/kg) of xylazine HCl and 4.0–7.1 mg/kg (5.0±0.6 mg/kg) of ketamine HCl. In the xylazine HCl-ketamine HCl combination, good myorelaxation was induced. The mean induction times for the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 2.8±1.5 min and 6.9±4.4 min, respectively. The mean immobilization times with the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 39.3±16.5 min and 58.8±34.2 min, respectively. A half dose of ketamine HCl in combination with xylazine HCl could also immobilize Japanese monkeys successfully. Administrations of 0.5 mg/kg i.v. and 1.0 mg/kg i.m. of yohimbine HCl as an antagonist to xylazine HCl at 30 min after the induction reduced the immobilization time to 31.4±0.5 min and 49.0±22.1 min, respectively. Yohimbine HCl appears to be an effective antagonist to combination anesthesia by xylazine HCl-ketamine HCl in the Japanese monkey.     

Reversal of Ketamine/Xylazine combination anesthesia by Atipamezole in olive baboons (Papio anubis)

Background  The potential of Atipamezole (ATI) to reverse Ketamine/Xylazine (KET/XYL) anesthesia in the Olive baboon ( Papio anubis ) was studied.
Methods  Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO₂) were monitored. Baboons were treated with: KET/XYL only, KET/XYL followed by 100 μg/kg ATI or by 200 μg/kg ATI administered 25 minutes after KET/XYL.
Results  Atipamezole rapidly reversed depressed HR and SAP (10 ± 5.2 minutes), RR (5 ± 2 minutes) and SpO₂ (3 ± 6 minutes) and significantly decreased MAT (13 ± 2.2 minutes) vs. KET/XYL alone (35 ± 5 minutes). Emesis was absent and salivation was observed after administration of 200 μg/kg ATI only.
Conclusions  Atipamezole at 100 μg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects.     

单纯右美托咪定滴鼻与水合氯醛复合右美托咪定滴鼻在脑瘫患儿MRI检查中的应用效果比较

目的:比较单纯右美托咪定滴鼻与水合氯醛复合右美托咪定滴鼻在脑瘫患儿核磁共振成像(MRI)检查中的应用效果。方法:收集我院2015年1月到2016年7月收治的160例脑瘫患儿,按照就诊号排序后取随机数字分为单纯组和复合组,每组各80例。单纯组给予右美托咪定2μg/kg滴鼻+生理盐水口服(0.1 mL/kg),复合组给予口服水合氯醛50 mg/kg+右美托咪定(2μg/kg)滴鼻,采用密歇根大学小儿镇静评分(UMSS)评价镇静效果、镇静成功率,检测和比较两组患儿给药前后心率(HR)、血氧饱和度(SpO_2)、呼吸频率(RR)及入睡时间、苏醒时间、检查时间与父母分离时间等。结果:给药前,两组UMSS评分比较差异无统计学意义(P0.05),给药15 min、30 min,复合组UMSS评分明显高于单纯组(P0.05);给药30 min时,复合组镇静成功率为98.8%,单纯组为91.3%,差异具有统计学意义(P0.05);两组给药前后HR、SpO_2、RR水平比较差异均无统计学意义(P0.05)。单纯组入睡、苏醒、检查时间及与父母分离时间长于复合组(P0.05)。结论:水合氯醛复合右美托咪定滴鼻在脑瘫患儿MRI检查中的镇静效果明显优于单纯右美托咪定滴鼻。     

Conformation and vasoreactivity of VIP in phospholipids: effects of calmodulin

The purpose of this study was to determine the conformation and vasorelaxant effects of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized phospholipid micelles (SSM) and whether calmodulin modulates both of these processes. Circular dichroism spectroscopy revealed that VIP is unordered in aqueous solution at room temperature but assumes appreciable α helix conformation in SSM. This conformational transition was amplified at 37°C and by a low concentration of calmodulin (0.1 nM). Suffusion of VIP in SSM elicited significant time- and concentration-dependent potentiation of vasodilation relative to that elicited by aqueous VIP in the in situ hamster cheek pouch (P < 0.05). This response was significantly potentiated by calmodulin (0.1 nM). Collectively, these data indicate that exogenous calmodulin interacts with VIP in SSM to elicit conformational transition of VIP molecule from a predominantly random coil in aqueous environment to α helix in SSM. This process is associated with potentiation and prolongation of VIP-induced vasodilation in the in situ peripheral microcirculation.     

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.     

Determination of the enantiomers of ketamine and norketamine in human plasma by enantioselective liquid chromatography-mass spectrometry

A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection has been developed and validated for the simultaneous determination of plasma concentrations of (R)- and (S)-ketamine, and (R)- and (S)-norketamine. The compounds were extracted from human plasma using solid-phase extraction and then directly injected into the LC-MS system for detection and quantification. Enantioselective separations were achieved on a liquid chromatographic chiral stationary phase based upon immobilized alpha(1)-acid glycoprotein (the Chiral AGP column). The separations were achieved using a mobile phase composed of 2-propanol-ammonium acetate buffer (10 mM, pH 7.6) (6:94, v/v), a flow-rate of 0.5 ml/min and a temperature of 25 degrees C. Under these conditions, the analysis time was 20 min. Detection of the ketamine, norketamine and bromoketamine (internal standard) enantiomers was achieved using selected ion monitoring at m/z 238.1, 224.1 and 284.0, respectively. Extracted calibration curves were linear from 1 to 125 ng/ml per enantiomer for each analyte with correlation coefficients better than 0.9993 and intra- and inter-day RSDs of less than 8.0%. The method was applied to samples from a clinical study of ketamine in pain management.     

Immobilization of adult male southern elephant seals (<Emphasis Type="Italic">Mirounga leonina</Emphasis>) during the breeding and molting periods using a tiletamine/zolazepam mixture and ketamine

Seventy-seven immobilizations were carried out on adult male southern elephant seals at Stranger Point, Isla 25 de Mayo (King George Island) using a combination of Zoletil^® (tiletamine and zolazepam) and ketamine in order to obtain biological samples. During 2006/2007, 22 males were immobilized at the beginning of their breeding period (EB), 19 of which were recaptured at the end of breeding (LB). Four were given only once at an unknown stage of breeding (USB) and 18 males were immobilized at the beginning of molting (BM). During 2007/2008, 14 adult males were immobilized at an USB. Zoletil^® was administered using an automatic discharge device, whereas ketamine was injected directly with a syringe, and was used only when the initial sedation was not enough to carry out the programmed sampling. The initial mean dose of Zoletil^® was 1,387 ± 304 mg, which represented 0.60 ± 0.14 mg/kg, range 0.36–1.05, n = 77. In 47 procedures, an average dose of 1.04 ± 0.66 mg/kg of ketamine was added. Mean immobilization time was 34 ± 14 min. In 25 out of the 77 procedures, males showed apnea, which lasted 8 ± 4 min (range 2–15 min). The necessary doses of Zoletil^® and ketamine to attain immobilization differed between stages. For animals taken twice, doses (mg/kg) of Zoletil^® and ketamine were significantly higher at the beginning than at the end of breeding. During molting, the doses of Zoletil^® given were significantly lower than those used during breeding, although the proportion of animals that required ketamine during molting was significantly higher than during breeding. Zoletil^® proved to be a safe immobilizing agent for field work on adult males of this species, given the wide range of doses used without any serious consequences. Furthermore, the addition of ketamine was useful when the initial sedation was not satisfactory or for prolonging the immobilization period in a practical and reliable way.     

Gas chromatography-isotope dilution mass spectrometry preceded by liquid-liquid extraction and chemical derivatization for the determination of ketamine and norketamine in urine

An analytical scheme using gas chromatography (GC)-isotope dilution mass spectrometry (MS) assisted by precedent liquid-liquid extraction (LLE) and chemical derivatization (ChD) is described for the simultaneous determination of ketamine (KT) and its major metabolite, norketamine (NK), in urine. The simultaneous ChD of the two analytes, one primary amine and one secondary amine, with pentafluorobenzoyl chloride (PFBC) has not only enhanced their instrumental responses and mass-spectrum uniqueness but also afforded more proper yet easier selection of qualifier and quantifier ions and hence achieved more evidential identification and quantitation. Thus, the regression calibration curves for KT and NK in urine are linear within 100-5000 ng/ml, with correlation coefficients typically exceeding 0.99 and NK curves exclusively showing larger slopes than KT curves. The method limits of detection (LODs) determined by two definitions for KT and NK range from 3 to 75 ng/ml, and limits of quantitation (LOQs) from 9 to 100 ng/ml. The mean recoveries (N = 3) calculated for the LLE/ChD of KT and NK from 50 and 100 microl, respectively, of a 100 microg/ml urinary spike vary from 71.0 to 97.8%, with NK consistently giving better recoveries than KT. The precisions (N = 3) calculated for the total analyses of four real-case samples are typically below 12.3%. GC-MS operated in the positive ion chemical ionization (PCI) mode can offer both qualitative and quantitative information complementary to those given by the EI mode. The proposed scheme is simple, effective, reliable, and robust. It may serve as a confirmatory protocol for forensic urine drug testing.     

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers

BACKGROUND: This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. METHODS: Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. RESULTS: Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. CONCLUSION: The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress.     

The involvement of nitric oxide in the analgesic effects of ketamine

We investigated the contribution of NO-cyclic GMP (cGMP) pathway to the antinociceptive effects of ketamine in mice by using the nitric oxide synthase inhibitor, nitro(g)- L-arginine methyl ester (L-NAME). Intraperitoneal (i.p.) (1, 5 or 10 mg/kg) or intrathecal (i.th.) (10, 30 or 60 microg/mouse) administration of ketamine produced dose-dependent antinociceptive effects in the acetic acid-induced writhing and formalin tests but not in the tail-flick nor in hot-plate tests. Pretreatment of mice with L-NAME (10 mg/kg, i.p.) which produced no antinociception on its own, significantly inhibited the antinociceptive effect of ketamine (1, 5 or 10 mg/kg, i.p.). However, L-NAME (30 microg/mouse) was given intrathecally, it neither modified the antinociceptive effect of i.th. ketamine (10, 30 or 60 microg/mouse) nor did it produce an antinociceptive effect alone. These data suggest that the activation of the NO-cGMP pathway probably at the supraspinal level, but not spinal level, contributes to the antinociceptive effects of ketamine.     

麻醉诱导时血压下降对术后恶心呕吐的影响

目的：观察麻醉诱导时血压下降与术后恶心呕吐的关系.方法：选择ASAⅠ-Ⅱ级的经腹胆囊切除术患者40例,按麻醉诱导时血压比基础值下降的程度分为2组,每组20例.A组：SBP比基础血压下降〉30%;B组：SBP比基础血压下降〈30%.术后随访病人48小时,记录病人恶心呕吐的发生情况.结果：麻醉诱导时血压下降对术后恶心呕吐有明显影响.结论：麻醉期间维持血流动力学稳定能降低PONV的发生.     

Partially antagonisable anaesthesia of the small hedgehog tenrec (Echinops telfairi) with medetomidine, midazolam and ketamine

It was purpose of this study to establish a safe and stable anaesthesia for the small hedgehog tenrec (Echinops telfairi) which can be used for short- and long-time interventions.

Therefore 29 small hedgehog tenrecs were anaesthetized between 30 min and 4.5 h with a combination of the ₂-agonist medetomidine (0.2 mg/kg), the benzodiazepine midazolam (3 mg/kg) and the dissociative anaesthetic ketamine (20 mg/kg) (MMK). All injections were administered subcutaneously (SC) in the area of the back by carefully lifting the animal's quills with a forceps. After SC injection of MMK animals lost their righting reflexes after 3.6 min (±1.12). Oxygen was supplemented to the animals’ nose and their body temperature was maintained constantly at 30 °C by a heating plate.

Values of respiratory rate, pulse rate and oxygen saturation during the experiment were statistically evaluated by ANOVA and post-hoc tests to a level of significance determined as 5%.

The animals had stable cardiovascular and respiratory values and good muscle relaxation.

Between the 15th and the 45th minute the level of anaesthesia was deep enough for surgical interventions. Respiratory rate in this phase was 29.6±8.1 breaths/min and pulse rate was about 81.9±20 beats/min.

MMK was partially antagonised with a combination of atipamezole (1 mg/kg) and flumazenile (0.2 mg/kg) (AF) SC. Time of complete recovery took about 8.8 min (8.76±4.31 min) after administering the antagonists.

The partially antagonisable combination of MMK produced a stable anaesthesia in small hedgehog tenrecs up to 4.5 h. Therefore MMK can be used for short time interventions as well as e.g. for long-lasting neurophysiological recordings, when animals should survive the trials.     

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.     

A dynamic X-ray diffraction study of anesthesia action. Thickening of the myelin membrane by n-pentane

The structural changes induced in the myelin sheath by $\text{n-}\text{pentane}$ nerve impulse blockage were studied by small-angle X-ray diffraction using a linear position-sensitive detector. The results show that the thickness of the myelin period lattice increases from 170 to 180 Å during $\text{n-}\text{pentane}$ treatment.     

不同时间段睡眠剥夺配合改良式水合氯醛保留灌肠法在婴幼儿肺功能检查中的效果分析

摘要 目的：探讨不同时间段睡眠剥夺配合改良式水合氯醛保留灌肠法在婴幼儿肺功能检查中的镇静效果。方法：前瞻性选取2018年2月~2020年8月本院收治并需行肺功能检查的婴幼儿临床资料,纳入194例婴幼儿作为研究对象,根据随机数字表法简单随机分为四组。对照组（n=48）不进行睡眠剥夺,短时段组（n=48）行短时段睡眠剥夺,中时段组（n=49）行中时段睡眠剥夺,长时段组（n=49）行长时段睡眠剥夺。对比四组婴幼儿的入睡时间、镇静效果及不良反应。结果：四组婴幼儿入睡时间的组间差异具有统计学意义（P＜0.05）。与对照组相比,联合睡眠剥夺干预的三组婴幼儿在10 min内进入睡眠的例数明显增多;随着睡眠剥夺时间增加,睡眠剥夺的三组婴幼儿超过30 min才进入睡眠的例数明显少于对照组。四组婴幼儿镇静效果的组间比较差异具有统计学意义（P＜0.05）;与对照组相比,联合睡眠剥夺干预的三组婴幼儿镇静效果明显升高,镇静总有效率均高于对照组（P＜0.05）。在实验期间,四组婴幼儿均出现不同类型的不良反应,各类型不良反应发生率及总发生率的组间比较,差异均无统计学意义（P>0.05）,但长时段组出现情绪烦躁的比例略高。结论：睡眠剥夺配合改良式水合氯醛灌肠法对婴幼儿具有良好的镇静效果,但长时段睡眠剥夺可能会使其情绪烦躁,需在检查完成后悉心安抚婴幼儿情绪。     

Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase

The functionality of the disintegrin-like/cysteine-rich domains of snake venom metalloproteinases (SVMPs) has been shown to reside in the cysteine-rich region, which can interact with VWA-containing proteins. Recently, the hyper-variable region (HVR) of the cysteine-rich domain was suggested to constitute a potential protein-protein adhesive interface. Here we show that recombinant proteins of HF3, a hemorrhagic P-III SVMP, containing the cysteine-rich domain (disintegrin-like/cysteine-rich and cysteine-rich proteins) but not the disintegrin-like protein were able to significantly increase leukocyte rolling in the microcirculation. Peptides from the HVR also promoted leukocyte rolling and this activity was inhibited by anti-alpha_M/beta₂ antibodies. These results show, for the first time, that the cysteine-rich domain and its HVR play a role in triggering pro-inflammatory effects mediated by integrins.