Helen L. Keates

Intraarticular and periarticular opioid binding in inflamed tissue in experimental canine arthritis

UNLABELLED Small-dose (1 mg) intraarticular morphine has been used successfully in many studies to provide long-lasting analgesia after arthroscopic knee surgery. We used radioligand binding to determine whether these effects could be mediated by opioid binding sites in the joint, particularly after the induction of inflammation. Inflammation was induced by the injection of oleyl alcohol (20 microL) in sterile peanut oil (0.25 mL) into the left radiocarpal joint of 27 dogs, and the dogs were euthanized at 12 h. The articular and periarticular tissues from both treated and control joints were collected, and membranes were prepared for equilibrium binding assays. The density of specific opioid binding was markedly enhanced (P < 0.05) in homogenates prepared from the treated relative to those from the control joint. The binding affinities (KD values) for morphine and naloxone (mean +/- SEM) were approximately one one-hundredth (79 +/- 17 nM and 124 +/- 5.5 nM, respectively) that of the corresponding published affinities in brain tissue. However, the binding site densities were approximately one hundred times larger (Bmax = 1032 +/- 265 and 543 +/- 51 fmol/mg of protein) than the respective published values in brain tissue. These findings imply that the opioid binding sites, found in the inflamed articular and periarticular tissues in this study, are similar to those of putative mu 3-opioid binding sites that appear to be present on cultured thymocytes and in the airways of rats and humans. IMPLICATIONS The high density of opioid binding sites found in inflamed canine joint tissue supports the clinical use of intraarticular opioids in the treatment of postoperative and chronic inflammatory joint pain.

Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog.

Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1×, 2×, 5×, 10× and 20× multiples of the labelled doses (2mg/kg for alfaxalone; 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1×) doses of each drug but became apnoeic at 5× dose of propofol versus 20× dose of alfaxalone. For propofol at 2× and 5× doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2×, 5× and 10× doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5×) than for propofol (2×) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone.

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

OBJECTIVE To determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin. STUDY DESIGN Prospective experimental study. ANIMALS Ten (five male and five female), adult, healthy, Standardbred horses. METHODS Horses were premedicated with acepromazine (0.03 mg kg(-1) IV). Twenty minutes later they received xylazine (1 mg kg(-1) IV), then after 5 minutes, guaiphenesin (35 mg kg(-1) IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg(-1) ). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1-5 (1 very poor, 5 excellent). RESULTS The median (range) induction and recovery scores were 4 (3-5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1-5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t(1/2) ), plasma clearance (Clp) and volume of distribution (V(d) ) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute(-1)  kg(-1) and 1.6 ± 0.4 L kg(-1) , respectively. CONCLUSIONS AND CLINICAL RELEVANCE Alfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.

A systematic review of the effects of euthanasia and occupational stress in personnel working with animals in animal shelters, veterinary clinics, and biomedical research facilities

BACKGROUND The study of occupational stress and compassion fatigue in personnel working in animal-related occupations has gained momentum over the last decade. However, there remains incongruence in understanding what is currently termed compassion fatigue and the associated unique contributory factors. Furthermore, there is minimal established evidence of the likely influence of these conditions on the health and well-being of individuals working in various animal-related occupations. OBJECTIVE To assess currently available evidence and terminology regarding occupational stress and compassion fatigue in personnel working in animal shelters, veterinary clinics, and biomedical research facilities. DATA SOURCE Studies were identified by searching the following electronic databases with no publication date restrictions: ProQuest Research Library, ProQuest Social Science Journals, PsycARTICLES, Web of Science, Science Direct, Scopus, PsychINFO databases, and Google Scholar. Search terms included (euthanasia AND animals) OR (compassion fatigue AND animals) OR (occupational stress AND animals). STUDY APPRAISAL AND SYNTHESIS Only articles published in English in peer-reviewed journals that included use of quantitative or qualitative techniques to investigate the incidence of occupational stress or compassion fatigue in the veterinary profession or animal-related occupations were included. On the basis of predefined criteria, 1 author extracted articles, and the data set was then independently reviewed by the other 2 authors. RESULTS 12 articles met the selection criteria and included a variety of study designs and methods of data analysis. Seven studies evaluated animal shelter personnel, with the remainder evaluating veterinary nurses and technicians (2), biomedical research technicians (1), and personnel in multiple animal-related occupations (2). There was a lack of consistent terminology and agreed definitions for the articles reviewed. Personnel directly engaged in euthanasia reported significantly higher levels of work stress and lower levels of job satisfaction, which may have resulted in higher employee turnover, psychological distress, and other stress-related conditions. LIMITATIONS AND CONCLUSIONS Results of this review suggested a high incidence of occupational stress and euthanasia-related strain in animal care personnel. The disparity of nomenclature and heterogeneity of research methods may contribute to general misunderstanding and confusion and impede the ability to generate high-quality evidence regarding the unique stressors experienced by personnel working with animals. The present systematic review provided insufficient foundation from which to identify consistent causal factors and outcomes to use as a basis for development of evidence-based stress management programs, and it highlights the need for further research.

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

OBJECTIVE To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate. STUDY DESIGN Prospective experimental study. ANIMALS Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg. METHODS Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. RESULTS The harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl(p) ) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg(-1) and 0.6 ± 0.2 L kg(-1) , respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively. CONCLUSIONS The anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life. CLINICAL RELEVANCE Alfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.

Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin

OBJECTIVE To compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin. STUDY DESIGN Randomized blinded cross-over experimental study. ANIMALS Six adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings. METHODS Each horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-1) . Premedication was with xylazine 0.5 mg kg(-1) and guaifenesin 35 mg kg(-1) . Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO(2) ) and carbon dioxide (PaO(2) ), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range). RESULTS There was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24-47) minutes for alfaxalone; 22 (18-35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38-67) minutes] compared with ketamine [35 (30-47)]. There was no statistical difference between treatments in effect on HR, PaO(2) or PaCO(2) although for both regimens, PaO(2) decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE Both alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.

Electromyography of some respiratory muscles in the horse

To investigate activity in respiratory muscles, insulated wire electrodes were used to record electromyographic activity in the costal diaphragm and in the intercostal, serratus ventralis, internal abdominal oblique, transversalis and rectus abdominis muscles in conscious horses and in the same animals when anaesthetised. Electromyographic activity was related to respiratory phases as recorded by a stethograph around the chest wall. The costal diaphragm showed tonic and inspiratory activity in both conscious and anaesthetised animals. The principal muscle actively involved in expiration was the transversalis muscle. Intercostal muscle activity, and any increased activity in the second part of either inspiration or expiration recorded in the conscious animal, was absent under anaesthesia. The very marked tonic activity found in the serratus ventralis muscle in standing horses disappeared during anaesthesia. It was concluded that any stabilisation of the chest wall contributed by activity in the serratus ventralis and intercostal muscles in conscious, standing horses is greatly reduced during anaesthesia.

Soluble arabinoxylan alters digesta flow and protein digestion of red meat-containing diets in pigs

OBJECTIVES The aim of this study was to investigate how a moderate increase in dietary meat content combined (or not) with soluble fibre would influence protein digestion as well as digesta characteristics and flow. METHODS Four groups of pigs were fed Western-style diets (high-protein/high-fat) containing two types of barbecued red meat, one with and one without a wheat arabinoxylan-rich fraction. After 4 wk, digesta samples were collected from small and large intestinal sites and analyzed for protein, amino acids, dry matter, and acid-insoluble ash. Tissue samples were also collected from each site. RESULTS Arabinoxylan consumption led to somewhat lower apparent protein digestibility within the small and large intestines as well as shorter mean retention times. This suggests that the lowered protein digestibility is due, at least partly, to shorter access time to digestive proteases and absorptive surfaces. Additionally, digesta mass was higher in pigs fed arabinoxylan while dry matter (%) was lower, indicating an increased digesta water-holding capacity due to the presence of a soluble dietary fiber. CONCLUSION Data showed that solubilized wheat arabinoxylan provides potential health benefits through decreased protein digestibility, increased digesta mass, and reduced mean retention time, even for diets with a moderately higher protein content. These factors are associated with efficiency of digestion and satiety, both of which have implications for prevention of obesity and other health disorders.

Elongate microparticles for enhanced drug delivery to ex vivo and in vivo pig skin

The delivery of therapeutics and cosmaceuticals into and/or through the skin is hindered by epidermal barriers. To overcome the skins barriers we have developed a novel cutaneous delivery method using high aspect ratio elongate microparticles (EMPs). Using ex vivo and in vivo pig skin we assess the penetration and delivery characteristics of the elongate microparticles. With reflectance confocal microscopy we observed that the elongate microparticles successfully penetrated the epidermis and upper dermis. Delivery was then assessed using two different length populations of EMPs, comparing their delivery profile to topical alone using sodium fluorescein and confocal microscopy. We observed a relatively uniform and continuous delivery profile in the EMP treated area within the upper layers of the skin--up to seven times greater than topical alone. Finally, we delivered two therapeutically relevant compounds (Vitamins A and B3), showing enhanced delivery using the EMPs. To our knowledge this is the first report using high aspect ratio elongate microparticles in this manner for enhanced topical delivery to the skin.

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

REASONS FOR PERFORMING THE STUDY The use of alfaxalone and medetomidine administered as an i.v. infusion to maintain anaesthesia has not previously been reported in the horse. OBJECTIVES To investigate the use of alfaxalone in hydroxpropyl-beta-cyclodextrin (Alfaxan) and medetomidine infusion as a field anaesthetic for short-term surgical procedures in the horse. HYPOTHESIS Alfaxalone-medetomidine anaesthesia is suitable for short-term field anaesthesia in horses. METHODS Eleven healthy colts underwent 45 min of anaesthesia with an i.v. infusion of alfaxalone (2 mg/kg bwt/h) and medetomidine (5 μg/kg bwt/h) for routine field castration. Horses were premedicated with i.v. acepromazine (0.03 mg/kg bwt), medetomidine (7 μg/kg bwt) and guaiphenesin (35 mg/kg bwt) before i.v. induction with alfaxalone (1 mg/kg bwt). Colts were intubated with an endotracheal tube and 100% oxygen insufflated at 10 l/min. The physiological variables monitored included pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases and the quality of the inductions and recoveries were scored. RESULTS Overall, the anaesthetic period and surgical conditions were acceptable and the quality of the anaesthetic inductions and recoveries was good to excellent. All colts stood on their first attempt (mean ± s.d.) 37 ± 13.5 min after the infusion was stopped. During anaesthesia, cardiopulmonary data, presented as range of mean values at each time point were: heart rate: 45-47 beats/min; mean blood pressure: 104-112 mmHg; respiratory rate: 8 breaths/min; PaO2 : 117-172 mmHg; PaCO2 : 50-56 mmHg and pH 7.34-7.37. CONCLUSIONS AND POTENTIAL RELEVANCE The co-administration of alfaxalone and medetomidine as an i.v. infusion after anaesthetic induction with alfaxalone was suitable for short-term field anaesthesia in the horse.