Effects of isoflurane concentration on basic echocardiographic parameters of the left ventricle in rats

Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations 相似文献   

Mass-spectrometry analysis of disflurane,propofol, and fentanyl in plasma and cerebrospinal fluid

Concentrations of anesthetic agents were measured in blood plasma and cerebrospinal fluid using mass spectrometry with a membrane interface. Sampling of biological fluids was performed during balanced inhalational (disflurane and fentanyl) anesthesia and total intravenous (propofol and fentanyl) anesthesia. A rapid test method for the concentration measurement of organic molecules in biological fluids is described. This method does not require long-term sample processing before injecting the sample into the mass spectrometer interface. The pervaporation properties (uptake, diffusion, and evaporation) of anesthetic agents from biological fluids in a silicone membrane were used in the mass spectrometry interface. We report on the possibility of using a mass spectrometer with a membrane interface for the measurement of the absolute concentration of anesthetic agents in blood plasma for study of the properties of the blood–brain barrier.     

四种麻醉药物对食蟹猴麻醉效果分析和选择应用

目的分析比对速眠新、氯胺酮、异氟烷和利多卡因4种不同麻醉药对食蟹猴的麻醉效果。方法总结实际工作中分别使用四种不同麻醉药物对食蟹猴作用的麻醉特点。结果速眠新、氯胺酮、异氟烷均能获得较好的麻醉效果,能满足不同手术、采样需要;局麻药利多卡因对食蟹猴麻醉的实际应用不理想。结论食蟹猴的手术及其他侵犯性操作等都应该考虑生物安全和动物福利要求,实行麻醉,但应根据食蟹猴实验内容要求和不同麻醉药特点选择合适的麻醉方法,确保人员和动物安全,实验结果不受影响。     

Effects of inhalational anesthesia on blood gases and pH in California sea lions

Despite the widespread use of inhalational anesthesia with spontaneous ventilation in many studies of otariid pinnipeds, the effects and risks of anesthetic‐induced respiratory depression on blood gas and pH regulation are unknown in these animals. During such anesthesia in California sea lions (Zalophus californianus), blood gas and pH analyses of opportunistic blood samples revealed routine hypercarbia (highest P_CO2 = 128 mm Hg [17.1 kPa]), but adequate arterial oxygenation (P_O2 > 100 mm Hg [13.3 kPa] on 100% inspiratory oxygen). Respiratory acidosis (lowest pH = 7.05) was limited by the increased buffering capacity of sea lion blood. A markedly widened alveolar‐to‐arterial P_O2 difference was indicative of atelectasis and ventilation‐perfusion mismatch in the lung secondary to hypoventilation during anesthesia. Despite the generally safe track record of this anesthetic regimen in the past, these findings demonstrate the value of high inspiratory O₂ concentrations and the necessity of constant vigilance and caution. In order to avoid hypoxemia, we emphasize the importance of late extubation or at least maintenance of mask ventilation on O₂ until anesthetic‐induced respiratory depression is resolved. In this regard, whether for planned or emergency application, we also describe a simple, easily employed intubation technique with the Casper “zalophoscope” for sea lions.     

Anesthesia for outpatient female sterilization

This issue of the Bulletin deals with the principles of anesthesia for outpatient female sterilization with emphasis on techniques for laparoscopy and minilaparotomy. General anesthesia techniques provide analgesia, amnesia, and muscle relaxation and are particularly useful for managing the anxious patient. Disadvantages include increased expense, need for specialized equipment, and highly trained personnel, and delayed recovery. Complications, though relatively rare, can be life-threatening and include aspiration of stomach contents, hypoxia, hypercarbia, hypotension, hypertension, cardiac arrhythmias, cardiorespiratory arrest, and death. There is no single preferred technique of general anesthesia, athough most anesthetists employ methods that allow rapid recovery of faculties, enabling the patient to be discharged soon after surgery. To accomplish this end, light anesthesia with sodium thiopental induction and nitrous oxide maintenance is often used. Short duration muscle relaxation with an agent such as succinylcholine supplements this technique. Other techniques include light anesthesia with inhalational anesthetic agents and the use of intravenous ketamine. Local anesthesia augmented by systemic and/or inhalational analgesia is supplanting general anesthesia techniques for laparoscopy in many locales. This approach is also particularly well-suited for minilaparotomy in developing countries, where it has achieved its greatest popularity. The local technique carries with it reduced morbidity and mortality but may not entirely relieve discomfort. The primary danger of local anesthesia is respiratory depression due to excessive narcosis and sedation. The operator must be alert to the action of the drugs and should always use the minimal effective dose. Although toxicity due to overdosage with local anesthetic drugs is occasionally experienced, allergic reactions to the amide-linkage drugs such as lidocaine or bupivacaine are exceedingly rare. For outpatient laparoscopy or minilaparotomy, local anesthesia with proper preoperative counselling and premedication should provide adequate relief of pain and is the method of choice, unless the patient cannot be examined awake or is totally uncooperative. The decision to utilize either general or local anesthesia should be made by the patient after thorough counselling by the surgical team. In many cases, the circumstances of the surgical environment will dictate the choice, but patient comfort and safety should always be the goal.     

Biomarkers of oxidative stress and endothelial dysfunction after tourniquet release in children

Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field and facilitate dissection. This prospective study was carried out to examine possible effect of different anesthesia techniques on oxidative stress and endothelial dysfunction connected with ischemia-reperfusion injury during extremity operations at children's age. Patients were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples for determination of the malondialdehyde in plasma and erythrocytes, protein carbonyl groups concentration as well as plasma nitrites and nitrates level and xanthine oxidase activity were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release, 5 and 20 min after tourniquet release. This study demonstrates that total intravenous anesthesia with propofol and regional anesthesia techniques provide better antioxidant defense and reduce endothelial dysfunction than general inhalational anesthesia with sevoflurane during tourniquet application in pediatric extremity surgery.     

UNDERSTANDING AND INTERPRETING HEMATOCRIT MEASUREMENTS IN PINNIPEDS

Hematocrit data are relatively easily obtained from blood samples of pinnipeds but differences in methodology and variable physiological conditions of the subjects can significantly alter their values. This two-fold problem makes comparative data and modeling efforts difficult. To quantify the difficulty of obtaining accurate and representative hematocrit values in pinnipeds, hematocrit was measured by both microcentrifugation and Coulter counter methods in a range of pinnipeds under a variety of physiological and handling conditions. The data show that the Coulter counter hematocrit values were 4%-15% higher than those measured by microcentrifugation. In addition, blood samples from restrained animals showed consistently elevated hematocrit values relative to resting subjects. A significant difference was also found between hematocrit values from pups and adults. Finally, hematocrit was shown to decline over the course of isofluorane anesthesia. Taken together, these results suggest that laboratory methodology, developmental state, and animal handling techniques can significantly alter hematocrit values in pinnipeds. Thus, modeling efforts that require representative hematocrit values, such as calculations of total blood oxygen stores, can be markedly impacted by variations in hematocrit measurement techniques and sampling regimes.     

Response of wild subantarctic fur seal (Arctocephalus tropicalis) females to ketamine and tiletamine-zolazepam anesthesia

This study is the first to compare the anesthetic effects of two cyclohexamines on free-ranging subantarctic fur seal (Arctocephalus tropicalis) females. From April to July 1999, 107 females were immobilized for tooth extraction and blood sampling, using either ketamine (Ketalar, n = 58) alone or tiletamine-zolazepam (Zoletil 100, n = 49) mixture. Animals were injected intramuscularly at mean doses of 2.1 mg/kg for ketamine and 1.1 mg/kg for tiletamine-zolazepam mixture. Individual response to both drugs was highly variable. The dosage required to achieve a satisfactory level of anesthesia was smaller for subantarctic fur seals than for most other species of seals and was less for animals in better body condition. Few side effects were observed during the trials, aside from mild tremors caused by ketamine, and respiratory depression or prolonged apnea caused by tiletamine-zolazepam. We recommend use of ketamine, especially by those with little experience in anesthesia of fur seals. However, precautionary measures should be taken, such as using low doses for animals in good body condition and being prepared for anesthetic emergencies to avoid any casualties.     

NARCOBIT: a newly developed inhalational anesthesia system for mice.

NARCOBIT is the first anesthetic system for mice and rats to incorporate a ventilator. Therefore, it is expected to improve the reliability of mice and rat experiments by accurately controlling and maintaining the depth of anesthesia. In this study, we used NARCOBIT for inducing inhalational anesthesia in mice and evaluated the changes in their hemodynamic parameters. ICR mice were anesthetized with 5% isoflurane and room air, followed by endotracheal intubation. Subsequently, they were mechanically ventilated, and anesthesia was maintained by 2% isoflurane for a 60-min period (maintenance state) using NARCOBIT. In study 1, the heart rate (HR) and mean arterial blood pressure (MAP) were measured. The skin blood flow (SBF) from the hind legs was continuously measured during the maintenance state. Subsequently, the concentration-dependent effects of isoflurane on MAP were examined. In study 2, blood samples were obtained from the abdominal aorta for blood gas analysis. The HR and MAP decreased after anesthesia but were stable during the maintenance state. Decreased MAP and concentration-dependent effects of isoflurane were observed. The SBF increased slightly during the maintenance state but this increase was insignificant. The blood gas analysis showed neither hypoxia nor hypercapnia. Since the use of NARCOBIT enables the anesthetic concentration of isoflurane to be easily changed, a suitable anesthesia depth can be obtained for experimental purposes. Therefore, we conclude that NARCOBIT can be used for providing inhalational anesthesia to mice.     

Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics

General anesthesia is a relatively safe medical procedure, which for nearly 170 years has allowed life saving surgical interventions in animals and people. However, the molecular mechanism of general anesthesia continues to be a matter of importance and debate. A favored hypothesis proposes that general anesthesia results from direct multisite interactions with multiple and diverse ion channels in the brain. Neurotransmitter-gated ion channels and two-pore K⁺ channels are key players in the mechanism of anesthesia; however, new studies have also implicated voltage-gated ion channels. Recent biophysical and structural studies of Na⁺ and K⁺ channels strongly suggest that halogenated inhalational general anesthetics interact with gates and pore regions of these ion channels to modulate function. Here, we review these studies and provide a perspective to stimulate further advances.     

0.5%盐酸罗哌卡因复合芬太尼腰麻在剖宫产术中的临床应用效果

目的:探讨0.5%盐酸罗哌卡因复合芬太尼腰麻在剖宫产术中临床应用效果。方法:选取自2015年01月~2015年05月择期在我院行剖宫产的产妇70例,随机分为观察组和对照组,每组35例。对照组采用0.5%盐酸罗哌卡因进行腰麻,观察组采用0.5%盐酸罗哌卡因复合芬太尼进行腰麻。比较两组的麻醉效果及产妇麻醉指标,记录两组麻醉前后血压及心率变化,并对比两组新生儿出生后1、5、10 min的Apgar评分。结果:观察组麻醉优良率为97.14%,明显高于对照组的85.71%(P0.05)。两组麻醉后30 min血压、心率与麻醉前相比,差异具有统计学意义(P0.05),且两组间比较差异具有统计学意义(P0.05)。观察组痛觉阻滞起效时间、痛觉恢复时间、运动阻滞起效时间、运动恢复时间与对照组相比,差异具有统计学意义(P0.05);观察组新生儿出生后1、5、10min Apgar评分均明显高于对照组(P0.05)。结论:0.5%盐酸罗哌卡因复合芬太尼腰麻应用于剖宫产术,能有效提升麻醉效果,麻醉阻滞起效快,持续时间长,有利于改善新生儿结局,具有临床推广意义。     

Time and energy constraints in pinniped lactation

Previous reviews have recognized patterns of lactation in pinnipeds divided along phylogenetic lines. This study extended previous models of lactation in pinnipeds by explicitly taking into account all the energetic costs to mothers. Based on an analysis of time-energy budgets, the feasible lactation strategy for a species can be shown to depend on body mass. Due to increased metabolic costs of maintenance, species with a large body mass cannot normally sustain lactation by foraging during lactation unless they have access to rich local prey resources. Consequently, large pinnipeds must normally sustain lactation from body reserves. This disadvantage is compensated in large pinnipeds by freedom to forage in support of offspring at greater range whereas small pinnipeds are restricted to foraging within the locality of the pupping colony. In the absence of correlations between major life-history variables and body mass in pinnipeds, the principal patterns of lactation are likely to be different solutions to the trade-off between foraging on a relatively rich prey resource at long range and foraging on a poorer prey resource within a restricted range. Hence phylogeny may be less important than adaptation in the evolution of pinniped lactation.     

Gastrointestinal Disturbances Associated with Withdrawal of Ataractic Drugs

The psychological effects of abrupt withdrawal of ataractic drugs have been studied by others. Physical symptoms also occur under such circumstances and include abdominal pain, nausea and vomiting. Forty patients were divided into four groups of 10, each group receiving one of the following drugs: chlorpromazine, thioridazine, perphenazine or chlorprothixene. This medication was then suddenly withdrawn. In each of the chlorpromazine and thioridazine groups, three patients had gastrointestinal symptoms within 48 hours, lasting one to eight days. One patient on chlorprothixene, 450 mg. daily, experienced symptoms for six days. Perphenazine withdrawal produced no such symptoms. Thioridazine has little antiemetic action but perphenazine is prescribed for vomiting; hence it seems unlikely that the reported symptoms are due to a rebound action on the vomiting centre.These findings are relevant to the situation of withdrawal of ataractics prior to administration of anesthetics and to drug studies involving cross-over from an active compound to a placebo. The increasing use of ataractics suggests that this additional diagnostic possibility should be considered in the presence of obscure gastrointestinal symptoms.     

A MORPHOLOGICAL CONSIDERATION OF THE RELATIONSHIPS OF PINNIPEDS TO OTHER CARNIVORANS BASED ON THE BONY TENTORIUM AND BONY FALX

The close relationships of pinnipeds to other carnivorans were studied based on morphological characteristics of the bony tentorium (BT) and bony falx (BF) of carnivorans. It appears to be an important characteristic of the Carnivora that the clear BT is present in almost all species including pinnipeds. The BF is present in all species of pinnipeds, and only in the genus Ursus among fissipeds observed.
The parietal bone of all otariids and odobenids observed shows an extremely characteristic form as compared with other carnivorans. The sagittal and squa-mous borders of the parietal bone of these groups are bridged by a thin bony plate which forms large portions of the BT and BF. In phocids, the aspects of the BT and BF vary among species, but are apparently distinct from those of otariids and odobenids.
The BT of carnivorans can be divided into four types which appear to be useful for classification of the Carnivora. On the basis of the BT and BF form, the Otariidae and Odobenidae appear to have a specific sister relationship to the Ursidae, while the Phocidae appears to have dose affinities to the Mustelidae. Morphological differences of the BT and BF among pinnipeds strongly support the diphyletic origin of pinnipeds.     

Anesthetics Affect the Cerebral Metabolic Response to Circulatory Catecholamines

Abstract: This study examined whether the effect of intravenous infusions of either epinephrine or norepinephrine on cerebral metabolic rate for oxygen (CMR o ₂) in the dog was modified by different anesthetics. Infusions of either epinephrine or norepinephrine at rates of 0.1-0.25 μ kg⁻¹min⁻¹ reversibly increased the CMR o ₂ by 17–23% during anesthesia with cyclopropane 20% and nitrous oxide 50% in oxygen, whereas infusions at rates of 0.1-25.0 μg-kg⁻¹-min⁻¹ had no effect in dogs anesthetized with other inhalational or intravenous agents. Cyclopropane/nitrous oxide also increased permeability of the blood-brain barrier to Evan's blue dye whereas the other anesthetics tested did not. It is concluded that epinephrine and norepinephrine crossed the blood-brain barrier during cyclopropane anesthesia, accounting for the increase in CMR o ₂. The authors speculate that cyclopropane may have increased blood-brain barrier permeability by a direct effect on endothelial cells or by affecting central adrenergic systems and that epinephrine or norepinephrine may increase CMR o ₂ either by a direct action on neuronal receptors or via metabolically coupled synaptic events.     

Thermodynamics of anesthetic/protein interactions. Temperature studies on firefly luciferase.

Firefly luciferase is a soluble enzyme which is unusually sensitive to general anesthetics. The inhibition of the highly purified enzyme by three inhalational and three alcohol general anesthetics has been studied as a function of temperature, in the range from 5 to 20 degrees C. Inhibition constants Ki were determined at different temperatures, and van't Hoff plots of ln (Ki) versus reciprocal absolute temperature were found to be linear for all agents. Analysis of these plots gave values for the standard Gibbs free energy, enthalpy and entropy changes for transferring each anesthetic from water to the anesthetic-binding pocket on the protein. The most striking finding was that the enthalpy changes were much more negative for anesthetics binding to the protein than for binding to lipids or simple solvents. Furthermore, amongst the set of anesthetics studied, it was found that increasing potency correlated with favorable enthalpy rather than entropy changes. We discuss our results with respect to the molecular mechanisms underlying general anesthesia.     

A Genetic and Mosaic Analysis of a Locus Involved in the Anesthesia Response of Drosophila Melanogaster

We describe a genetic and behavioral analysis of several alleles of har38, a mutant with altered sensitivity to the general anesthetic halothane. We obtained a P-element-induced allele of har38 and generated several excision alleles by remobilizing the P element. The mutants narrow abdomen (na) and har85 are confirmed to be allelic to har38. Besides a decreased sensitivity to halothane, all mutant alleles of this locus cause a characteristic walking behavior in the absence of anesthetics. We have quantified this behavior using a geotaxis apparatus. Responses of the mutant alleles to different inhalational anesthetics were tested. The results strongly favor a multipathway model for the onset of anesthesia. Mosaic flies were tested for their response to halothane and checked for their abnormal walking behavior. The analysis suggests that both the behaviors are exhibited only by such mosaics as have the entire head of mutant origin. It is likely that this focus represents an element of a common pathway in the anesthetic response to several inhalational anesthetics but not all. This result is the first demonstration of regional specificity in the CNS of any animal for general anesthetic action.     

Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children.

To assess effects of anesthesia and opioids, we studied 13 children with obstructive sleep apnea (OSA, age 4.0 +/- 2.2 yr, mean +/- SD) and 24 age-matched control subjects (5.8 +/- 4.0 yr). Apnea indexes of children with OSA were 29.4 +/- 18 h-1, median 30 h-1. Under inhalational anesthetic, closing pressure at the mask was 2.2 +/- 6.9 vs. -14.7 +/- 7.8 cmH2O, OSA vs. control (P < 0.001). After intubation, spontaneous ventilation was 115.5 +/- 56.9 vs. 158.7 +/- 81.6 ml x kg-1 small middle dot min-1, OSA vs. control (P = 0.02), despite elevated PCO2 (49.3 vs. 42.1 Torr, OSA vs. control, P < 0.001). Minute ventilation fell after fentanyl (0.5 microg/kg iv), with central apnea in 6 of 13 OSA cases vs. 1 of 23 control subjects (P < 0.001). Consistent with the finding of reduced spontaneous ventilation, apnea was most likely when end-tidal CO2 exceeded 50 Torr during spontaneous breathing under anesthetic. Thus children with OSA had depressed spontaneous ventilation under anesthesia, and opioids precipitated apnea in almost 50% of children with OSA who were intubated but breathing spontaneously under inhalational anesthesia.     

FLIPPERS AND PINNIPED PHYLOGENY: HAS THE PROBLEM OF CONVERGENCE BEEN OVERRATED?

The phylogenetic relationships of the major groups of pinnipeds are of longstanding controversy. According to prevailing paleontological opinion, pinnipeds comprise two distinct lineages of independent terrestrial carnivoran origin, A logical correlate of this view is that an enormous degree of convergence accounts for the striking resemblances of these groups.
It has been generally supposed that derived similarities common to pinnipeds are independently acquired adaptations to a highly constraining environment. This has not been adequately substantiated. Moreover, considerable evidence favors a contrary conclusion. Acceptance of convergence necessarily rests on demonstration that taxa possessing characters suspected to be convergent are in fact not mutal nearest allies. In the absence of such phylogenetic information, shared derived characters are indicative of common ancestry irrespective of whether they are deemed "functionally important." Given meager support for the proposition that pinnipeds are related to different terrestrial lineages, it is currently more judicious to regard the group's origin as monophyletic. In addition to the presumed prevalence of convergence, biogeography, the high degree of morphological divergence of phocids, and the aberrant nature of phocines have improperly contributed to acceptance of independent pinniped origins.     

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

Background

Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model.

Methods

Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check.

Results

A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated.

Conclusions

For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep.