The investigation of antidepressant and anxiolytic effects of pregabalin and its mechanisms of action in rats.

OBJECTIVES: Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use. METHODS: Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed. RESULTS: In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance. CONCLUSION: PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.

Requirement for Discharge in the Care of a Responsible Adult in Procedural Sedation in the Emergency Department: Necessity or Potential Barrier to Health Equity?

BACKGROUND: Procedural sedation is commonly practiced by emergency physicians to facilitate patient care in the emergency department (ED). Although various guidelines have modernized our approach to procedural sedation, many procedural sedation guidelines and practices still often require that patients be discharged into the care of a responsible adult. DISCUSSION: Such requirement for discharge often cannot be met by underserved and undomiciled patients. Benzodiazepines, opioids, propofol, ketamine, "ketofol," etomidate, and methohexital have all been utilized for procedural sedation in the ED. For patients who may require discharge without the presence of an accompanying responsible adult, ketamine, propofol, methohexital, "ketofol," and etomidate are ideal agents for procedural sedation given rapid onsets, short durations of action, and rapid recovery times in patients without renal or hepatic impairment. Proper pre- and postprocedure protocols should be utilized when performing procedural sedation to ensure patient safety. Through the use of appropriate medications and observation protocols, patients can safely be discharged 2 to 4 h postprocedure. CONCLUSION: There is no pharmacodynamic or pharmacokinetic basis to require discharge in the care of a responsible adult after procedural sedation. Thoughtful medication selection and the use of evidence-based pre- and postprocedure protocols in the ED can help circumvent this requirement, which likely disproportionally impacts patients who are of low socioeconomic status or undomiciled.

A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms.

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine's neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in seven canonical frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Our beta-HMM framework provides a useful tool for experimental data analysis. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma and slow-delta activities. The mean duration of the gamma activity was 2.2s([1.7,2.8]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.5s([1.7,3.6]s) for the human subjects. The mean duration of the slow-delta activity was 1.6s([1.2,2.0]s) and 1.0s([0.8,1.2]s) for the two NHPs, and 1.8s([1.3,2.4]s) for the human subjects. Our characterizations of the alternating gamma slow-delta activities revealed five sub-states that show regular sequential transitions. These quantitative insights can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal.

The potential of 1H-MRS in CNS drug development.

RATIONALE: Proton magnetic resonance spectroscopy (1H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including glutamate and GABA. This non-invasive method has promise in developing centrally acting drugs, as it can be performed repeatedly within-subjects and be used to translate findings from the preclinical to clinical laboratory using the same imaging biomarker. OBJECTIVES: This review focuses on the utility of single-voxel 1H-MRS in developing novel glutamatergic or GABAergic drugs for the treatment of psychiatric disorders and includes research performed in rodent models, healthy volunteers and patient cohorts. RESULTS: Overall, these studies indicate that 1H-MRS is able to detect the predicted pharmacological effects of glutamatergic or GABAergic drugs on voxel glutamate or GABA concentrations, although there is a shortage of studies examining dose-related effects. Clinical studies have applied 1H-MRS to better understand drug therapeutic mechanisms, including the glutamatergic effects of ketamine in depression and of acamprosate in alcohol dependence. There is an emerging interest in identifying patient subgroups with 'high' or 'low' brain regional 1H-MRS glutamate levels for more targeted drug development, which may require ancillary biomarkers to improve the accuracy of subgroup discrimination. CONCLUSIONS: Considerations for future research include the sensitivity of single-voxel 1H-MRS in detecting drug effects, inter-site measurement reliability and the interpretation of drug-induced changes in 1H-MRS metabolites relative to the known pharmacological molecular mechanisms. On-going technological development, in single-voxel 1H-MRS and in related complementary techniques, will further support applications within CNS drug discovery.

Behavioral economic analysis of the effects of N-substituted benztropine analogs on cocaine self-administration in rats.

RATIONALE AND OBJECTIVES: Benztropine (BZT) analogs and other atypical dopamine uptake inhibitors selectively decrease cocaine self-administration at doses that do not affect responding maintained by other reinforcers. Those effects were further characterized in the current study using a behavioral economic assessment of how response requirement (price) affects reinforcers obtained (consumption) in rats. METHODS: Two groups of rats were trained to press levers with food (45-mg pellet) or cocaine (0.32 mg/kg/injection) reinforcement under fixed-ratio (FR) 5-response schedules. In selected sessions, the FR requirement was increased (5-80) during successive 20-min components to determine demand curves, which plot consumption against price. An exponential function was fitted to the data to derive the consumption at zero price (Q 0) and the rate of decrease in consumption (essential value, EV) with increased price. The BZT analogs, AHN1-055, AHN2-005, JHW007 (3.2-10 or 17.8 mg/kg, each), vehicle, or comparison drugs (methylphenidate, ketamine), were administered i.p. before selected demand-curve determinations. RESULTS: Consumption of cocaine or food decreased with increased FR requirement. Each drug shifted the demand curve rightward at the lowest doses and leftward/downward at higher doses. The effects on EV and Q 0 were greater for cocaine than for food-reinforced responding. Additionally, the effects of the BZT analogs on EV and Q 0 were greater than those obtained with a standard dopamine transport inhibitor, methylphenidate, and the NMDA antagonist, ketamine (1.0-10.0 mg/kg, each). With these latter drugs, the demand-curve parameters were affected similarly with cocaine and food-maintained responding. CONCLUSIONS: The current findings, obtained using a behavioral economic assessment, suggest that BZT analogs selectively decrease the reinforcing effectiveness of cocaine.

Ketamine metabolites with antidepressant effects: Fast, economical, and eco-friendly enantioselective separation based on supercritical-fluid chromatography (SFC) and single quadrupole MS detection.

Increasing evidence accumulates that metabolites of the dissociative anesthetic ketamine contribute considerably to the biological effects of this drug and could be developed as next generation antidepressants, especially for acute treatment of patients with therapy-refractory major depression. Analytical methods for the simultaneous determination of the plethora of hydroxylated, dehydrogenated and/or demethylated compounds formed after administration of ketamine hydrochloride are a prerequisite for future clinical investigations and a deeper understanding of the individual role of the isomers of these metabolites. In this study, we present development and validation of a method based on supercritical-fluid chromatography (SFC) coupled to single quadrupole MS detection that allows the separation of ketamine as well as all of its relevant metabolites detected in urine of healthy volunteers. Inherently to SFC methods, the run times of the novel protocol are four times shorter than in a comparable HPLC method, the use of organic solvents is reduced and we were able to demonstrate and validate the successful enantioselective separation and quantification of R- and S-ketamine, R- and S-norketamine, R- and S-dehydronorketamine and (2R,6R)- and (2S,6S)-hydroxynorketamine isomers differing in either constitution, stereochemistry, or both, in one run. The developed method may be useful in investigating the antidepressant efficacy of ketamine in clinical trials.

Echocardiographic Assessment of the Alterations in Pulmonary Blood Flow Associated with Ketamine and Etomidate Administration in Children with Tetralogy of Fallot.

BACKGROUND: Despite widespread uses of ketamine, the clinical studies determining its effect on pulmonary blood flow in children with tetralogy of Fallot (TOF) are lacking. Furthermore, the quantification of pulmonary blood flow is not possible in these patients, because pulmonary artery catheter is contraindicated. Therefore, the purpose of this study was to evaluate the changes in pulmonary blood flow by intra-operative transesophageal echocardiography after ketamine or etomidate administration in children with TOF. METHODS: Eleven children each in the two clinical variants of TOF (group A-moderate to severe cyanosis; group B-mild to minimal cyanosis) undergoing intracardiac repair were prospectively studied after endotracheal intubation. A single bolus dose of ketamine (2 mg/kg) and etomidate (0.3 mg/kg) was administered in a random order after 15 minute interval. Hemodynamic, arterial blood gas, and echocardiographic measurements were obtained at 7 consecutive times (T) points (baseline, 1, 2, 4, 6, 8, and 15 minutes after drug administration). RESULTS: Ketamine produced a significant reduction in VTI-T (velocity time integrals total of left upper pulmonary vein), RVOT-PG (right ventricular outflow tract peak gradient), and MG (mean gradient) in group A while those in group B had a significant increase in VTI-T, RVOT-PG, and RVOT-MG at time (T1, T2, T4, and T6; P = 0.00). This divergent behavior, however, was not observed with etomidate. CONCLUSION: Etomidate does not change pulmonary blood flow. However, ketamine produces divergent effects; it increases pulmonary blood flow in children with minimal cyanosis and decreases pulmonary blood flow in children with moderate to severe cyanosis.

Quantitative assessment of pupillary light reflex in normal and anesthetized dogs: a preliminary study.

The purpose of this study was to quantitatively assess the pupillary light reflex (PLR) in normal and anesthetized dogs using a pupillometer. Eleven dogs (20 eyes) of various breeds were included. PLRs were measured with a handheld pupillometer in dim light before and during anesthesia. Anesthesia was conducted with atropine, xylazine and ketamine. Parameters of pupillometry included neurological pupil index (NPi), pupil size, percent of change (%CH), latency (LAT), constriction velocity (CV), maximum constriction velocity (MCV) and dilation velocity (DV). NPi,%CH, CV and MCV were significantly decreased during anesthesia compared with the pre-anesthesia data. The results suggest that atropine-xylazine-ketamine combination anesthesia depresses the PLR. Additionally, this study demonstrates the feasibility of the use of a pupillometer in dogs.

Withdrawal assessment following subchronic oral ketamine administration in Cynomolgus macaques.

Recently there is increased regulatory interest in the assessment of physical dependence and withdrawal as part of the safety assessment for novel therapeutic entities. Choosing appropriate and sensitive parameters to detect withdrawal syndromes, and relevant positive control comparator drugs that can be administered in the same manner as the test agent, are critical study design elements. Pilot studies to determine the effects of oral ketamine in cynomolgus monkeys during, and following cessation of treatment, were explored. Detailed behavioral observations (both remote and interactive), food consumption, and body weight and temperature, were assessed during the dose-ranging, repeat dose (5 or 14 days), and withdrawal phases (3 or 5 days). Doses explored during dose-ranging included 20, 40, 100, or 200 mg/kg ketamine; subsequent withdrawal assessments were conducted following repeat dosing of 150 mg/kg. In the 14-day dosing study, exposure to ketamine and norketamine was assessed following 8 days of dosing. Administration of 150 mg/kg ketamine produced decreased activity, loss of balance, ataxia, hunched posture, nystagmus, lateral recumbence, and changes in alertness levels during dosing phases. When ketamine was withdrawn, increased reactivity, increased activity, and stereotypic behaviors were demonstrated that were absent during baseline or the dosing phase of the studies.

Chemical immobilisation of free-ranging Pampas foxes (Pseudalopex gymnocercus): Assessment of ketamine-xylazine and tiletamine-zolazepam combinations.

Two protocols to immobilise free-ranging Pampas foxes for ear-tagging or radio-collaring were evaluated. One hundred fifteen foxes were injected with ketamine-xylazine (K-X) and thirteen with tiletamine-zolazepam (T-Z). The use of both T-Z and K-X combinations typically resulted in a smooth induction and recovery. In 86% of the cases K-X protocol was judged effective (mean±SD, K: 10.7±3.3mg/kg, X: 1.0±1.0mg/kg) while T-Z protocol was judged effective in 92% of the cases (T: 3.6±1.05mg/kg, Z: 3.6±1.05mg/kg). The primary differences between the two drug combinations were that the time necessary for the complete recovery was longer with T-Z, and thermic problems were found more frequently with K-X. Additionally, our results suggest that thermic stress may be a relatively frequent complication for Pampas foxes. This study provides baseline data on some physiologic variables in Pampas foxes captured with different methods and drugs in field conditions.

Avaliação da S(+)-cetamina no tratamento da dor neuropática e qualidade de vida em portadores de hanseníase / Assessment of the S (+) ketamine in the treatment of neuropathic pain and quality of life in patients with leprosy

A dor neuropática é uma síndrome dolorosa crônica, que ocorre muito frequentemente em pacientes com hanseníase, de difícil tratamento. Objetivou-se avaliar o efeito terapêutico da S(+)-cetamina na dor neuropática e qualidade de vida em portadores de hanseníase atendidos em ambulatórios em São Luís - MA. Estudo experimental tipo ensaio clínico, prospectivo, aleatório, duplamente cego, controlado por placebo, com 34 pacientes distribuídos aleatoriamente em um dois grupos, cetamina e placebo por três meses e randomizados por numeração sequenciada. A dor foi avaliada por meio de escala analógica visual (EAV) nas seis visitas quinzenais (1, 2, 3, 4, 5 e 6), e pelo inventário DN4, na visita 1 e 6, com distribuição da S(+)-cetamina e o analgésico de resgate e avaliado os efeitos adversos em cada visita. Realizou-se a coleta de 15mL de sangue para exames de segurança na visita 1 e 6 e para quantificação de citocinas plasmáticas IL-1, IL-6 e TNFα, nas visitas 1, 2, 4 e 6. Foi também, avaliada a qualidade de vida por meio do questionário WHOQOL-Bref nas visitas 1 e 6. Os resultados demostraram predominância do sexo feminino, idade de 18 a 29 anos, pardos, solteiros, renda de 2 a 4 salários mínimos; e média de 7,78±2,21 anos de estudo. Na avaliação da dor pela EAV os dois grupos apresentaram uma redução dos escores médios de dor ao longo do tempo, e mostrou significância estatística p < 0,05. Entretanto não foi observada diferença estatística para os escores de dor entre os grupos e também, em relação ao uso do medicamento analgésico (codeína) de resgate. Houve redução significante nos escore de DN4 no grupo placebo em relação às avaliações iniciais e finais comparadas à cetamina, ainda os escores iniciais do DN4 foram significativamente menores no grupo placebo, nas avaliações de antes e depois do uso da S(+)-cetamina. Na avaliação da qualidade de vida nos domínios físico, psicológico, relações sociais e meio ambiente, não se observou diferença estatisticamente ...

Neuropathic pain is a chronic pain syndrome of difficult treatment, occurring frequently in patients with leprosy. The objective of this study was to evaluate the therapeutic effect of S(+)-ketamine on neuropathic pain and quality of life in patients with leprosy seen at an outpatient clinic in São Luís - Ma. Experimental study clinical trial, prospective, randomized, double-blind, placebo-controlled trial with 34 patients in a randomized two groups, ketamine and placebo for three months and randomized by sequential numbering. Pain was evaluated using a visual analogue scale (VAS) on six bimonthly visits (1, 2, 3, 4, 5 and 6), and using the DN4 questionnaire on visits 1 and 6, with distribution of S (+)-ketamine and rescue analgesic and adverse effects assessed at each visit. Blood (15ml) was drawn from patients for safety tests on visits 1 and 6, and on visits 1, 2, 4 and 6, to cytokines IL-1, IL-6 and TNFα. Quality of life was also evaluated using WHOQOL-Bref on visits 1 and 6. Results showed most subjects female, age 18 and 29 years of age, pardo ethnicity, single, income between 2 and 4 minimum salaries, and a mean 7.78±2.21 years of education. In the assessment of pain by VAS both groups showed a reduction in mean pain scores over time, and showed statistical significance p <0.05. However there was no statistical difference in pain scores between groups and also in relation to the use of analgesic medication (codeine). There was significant reduction in DN4 score in the placebo group compared to the initial and final evaluations compared to ketamine, although the initial DN4 scores were significantly lower in the placebo group, the assessments before and after the use of S (+)-ketamine. In evaluating the quality of life in the physical, psychological, social relationships and environment, there was no statistically significant difference between groups. The amounts of IL-1, IL-6 and TNF-α in serum of four collections of ketamine and placebo ...

Assessment of parameters influencing the blood flow velocities in cerebral arteries of the rat using ultrasonographic examination.

OBJECTIVES: Rat models of cerebrovascular diseases are used for a variety of human pathologies comprising ischemic stroke or subarachnoid hemorrhage. Whereas in neuro-intensive care, Doppler ultrasonographic examination of major cerebral arteries is a common diagnostic tool, only few data exist concerning the animal model. We therefore studied cerebral blood flow velocities in the rat by ultrasonographic triplex mode. METHODS: Female Wistar rats underwent a large craniectomy and baseline values for blood flow velocities were obtained by 399 examinations in 52 animals. Vessel diameters were assessed by 301 examinations in 39 animals. Finally, in 26 animals, continuous measurements of blood flow velocities were performed. For a duration of more than 30 minutes, values in the anterior trunk, the left carotid artery and the basilar artery were obtained every 60-90 seconds with simultaneous detection of heart rate. RESULTS: Blood flow velocities in the anterior part of cerebral circulation were faster than those in the posterior part and showed higher standard deviation. Flow velocities in arteries belonging to the anterior circulation changed in relation to carotid flow velocity and heart rate, whereas the velocity in the basilar artery showed much lower correlation to carotid flow velocity or heart rate. DISCUSSION: Ultrasonographic triplex mode examination of cerebral vessels offers a reproducible method to study rat cerebral blood flow velocities and vessel diameters. In combination with monitoring of systemic hemodynamic parameters, it can provide a detailed description of the vascular response to drugs, experimental stroke or subarachnoid hemorrhage.

Method of assessment of the dynamics of salivary function in rats during the experiment.

The dynamics of salivary function was studied on 80 laboratory rats. It was found that construction of a graph showing the dynamics of stimulated salivation in small laboratory animals could be successfully used in various studies.

Assessment of serum enzymatic markers of cardiomyocytes injury in female dogs submitted to ketamine S(+), atropin and xylazine association / Mensuração da atividade sérica de marcadores de lesão cardíaca em cadelas anestesiadas com cetamina S(+), atropina e xilazina

PURPOSE: To assessment of the aspartate aminotransferase (AST), creatine kinase (CK) and creatine kinase isoenzyme fraction MB (CK-MB) serum activity in female dogs anesthetized with ketamine S (+), atropine and xylazine in several associations. METHODS: Twenty three healthy female dogs randomly distributed in four groups named as GI (n=6), GII (n=6), GIII (n=6) and GIV (n=5) were treated respectively with atropine and ketamine S(+) (0.04mg/kg; 10 mg/kg); ketamine S(+) (10 mg/kg); atropine, xylazine and ketamine S(+) (0.04mg/kg; 1.1 mg/kg; 10 mg/kg) and xylazine and ketamine S(+) (1.1 mg/kg; 10 mg/kg). AST, CK and CK-MB serum activity measurement before pre-medication (M0) and one, two, three, six, 12, 24, 36 hours after. RESULTS: There was no significant change in AST, CK e CK-MB serum activity among groups. However, CK serum activity in relation to moments within the groups was increased in all groups over the time in spite of treatment, except GI. In relation to CK-MB activity, in the moments within the group, it was observed an increase compared to baseline in all groups. CONCLUSION: Creatine kinase and creatine kinase fraction MB isoenzyme showed changes in their mean values remained higher than baseline for a longer time in GIII and GIV.

OBJETIVO: Determinar a atividade sérica de AST, CK e CK-MB em cadelas anestesiadas com cetamina S (+), atropina e xilazina em diferentes associações. MÉTODOS: Vinte e três cadelas saudáveis foram distribuídas ao acaso em quarto grupos denominados GI (n=6), GII (n=6), GIII (n=6) e GIV (n=5) tratados respectivamente com atropina e cetamina S (+) (0,04mg/kg; 10 mg/kg); cetamina S (+) (10 mg/kg); atropina, xilazina e cetamina S (+) (0,04mg/kg; 1,1 mg/kg; 10 mg/kg) exilazina e cetamina S (+) (1,1 mg/kg; 10 mg/kg). A atividade sérica de AST, CK e CK-MB foi determinada antes da pré-medicação (M0) e uma, duas, três seis, 12, 24 e 36 horas após M0. RESULTADOS: Não foram encontradas mudanças significativas na atividade sérica de AST, CK e CK-MB entre grupos. Entretanto, entre momentos houve aumento da atividade sérica de CK para todos os grupos, exceto em GI.Com relação a atividade sérica de CK-MB, observou-se ao longo dos momentos aumento significativo com relação aos valores basais em ambos os grupos. CONCLUSÃO: Alterações significativas foram observadas com relação à atividade sérica de CK e CK-MB em todos os tratamentos, mantendo-se elevada por um período maior nos grupos GIII e GIV.

Assessment of serum enzymatic markers of cardiomyocytes injury in female dogs submitted to ketamine S(+), atropin and xylazine association.

PURPOSE: To assessment of the aspartate aminotransferase (AST), creatine kinase (CK) and creatine kinase isoenzyme fraction MB (CK-MB) serum activity in female dogs anesthetized with ketamine S (+), atropine and xylazine in several associations. METHODS: Twenty three healthy female dogs randomly distributed in four groups named as GI (n=6), GII (n=6), GIII (n=6) and GIV (n=5) were treated respectively with atropine and ketamine S(+) (0.04 mg/kg; 10 mg/kg); ketamine S(+) (10 mg/kg); atropine, xylazine and ketamine S(+) (0.04 mg/kg; 1.1 mg/kg; 10 mg/kg) and xylazine and ketamine S(+) (1.1 mg/kg; 10 mg/kg). AST, CK and CK-MB serum activity measurement before pre-medication (M0) and one, two, three, six, 12, 24, 36 hours after. RESULTS: There was no significant change in AST, CK e CK-MB serum activity among groups. However, CK serum activity in relation to moments within the groups was increased in all groups over the time in spite of treatment, except GI. In relation to CK-MB activity, in the moments within the group, it was observed an increase compared to baseline in all groups. CONCLUSION: Creatine kinase and creatine kinase fraction MB isoenzyme showed changes in their mean values remained higher than baseline for a longer time in GIII and GIV.

Effects of anesthesia on echocardiographic assessment of left ventricular structure and function in rats.

Echocardiography is an essential diagnostic tool for accurate noninvasive assessment of cardiac structure and function in vivo. However, the use of anesthetic agents during echocardiographic studies is associated with alterations in cardiac anatomical and functional parameters. We sought to systematically compare the effects of three commonly used anesthetic agents on echocardiographic measurements of left ventricular (LV) systolic and diastolic function, LV dimensions, and LV mass in rats. Adult male Fischer 344 rats underwent echocardiographic studies under pentobarbital (PB, 25 mg/kg i.p.) (group I, n = 25), inhaled isoflurane (ISF, 1.5%) (group II, n = 25),or ketamine/xylazine (K/X, 37 mg/kg ketamine and 7 mg/kg xylazine i.p.) (group III, n = 25) anesthesia in a cross-over design. Echocardiography was also performed in an additional group of unanesthetized conscious rats (group IV, n = 5). Postmortem studies were performed to validate echocardiographic assessment of LV dimension and mass. Rats in group I exhibited significantly higher LV ejection fraction, fractional shortening, fractional area change, velocity of circumferential fiber shortening corrected for heart rate, and heart rate as compared with groups II and III. LV end-diastolic volume, end-diastolic diameter, and cross-sectional area in diastole were significantly smaller in group I compared with groups II and III. Cardiac output was significantly lower in group III compared with groups I and II. Postmortem LV mass measurements correlated well with echocardiographic estimation of LV mass for all anesthetic agents, and the correlation was best with PB anesthesia. Limited echocardiographic data obtained in conscious rats were similar to those obtained under PB anesthesia. We conclude that compared with ISF and K/X anesthesia, PB anesthesia at a lower dose yields echocardiographic LV structural and functional data similar to those obtained in conscious rats. In addition, PB anesthesia also facilitates more accurate estimation of LV mass.

The use and assessment of ketamine-medetomidine-butorphanol combinations for field anaesthesia in wild European badgers (Meles meles).

OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN: Prospective randomized 'blinded' experimental trial. METHODS: The quality of induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed in 93 badgers, given either one of three ketamine (K)-medetomidine (M)-butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B - M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1), or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the combination administered. Physiological variables (heart and respiratory rates and rectal temperature) were measured at 5-minute intervals during anaesthesia. Gingival mucus membrane colour was also recorded. RESULTS: Induction to anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality did not differ between techniques. Ketamine used alone gave the poorest score for anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane colour were higher in animals anaesthetized with ketamine alone. Rectal temperature did not differ significantly between the techniques at any time during anaesthesia. Ketamine used alone produced the poorest quality of recovery. CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame several side effects associated with ketamine anaesthesia, but at the expense of more variable induction times, lower HRs, and poorer mucus membrane coloration.