br Conflict of interest statement br Acknowledgements

Conflict of interest statement

This work has been funded by the following grant: BFU2009-11118 from the Ministerio de Ciencia e Innovación (Spain) and 2011 CTP 00032 from the Generalitat de Catalunya (Spain). Noemí Mañé (AP2012-0897) is supported by the Ministerio de Ciencia e Innovación (Spain) and Francisco Fernández (2014FI_B00415) by the Generalitat de Catalunya (Spain). Diana Gallego is supported by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en red de enfermedades hepáticas y digestivas (CIBERehd).

Bovine herpesvirus type 1 (BoHV-1) is an alpha-herpesvirus responsible for respiratory disease, abortions and genital disorders in cattle (Tikoo et al., 1995). BoHV-5, a closely related alpha-herpesvirus, is the causative agent of meningoencephalitis in calves (Pérez et al., 2002), which is highly prevalent in South America. Unlike BoHV-5, BoHV-1 has been reported only occasionally as responsible for bovine encephalitis (Meyer et al., 2001). However, several cases of neurological disease in cattle have recently been attributed to BoHV-1 (Silva et al., 2007; Rissi et al., 2008).
Neurotropic alpha-herpesviruses reach the SW033291 via the trigeminal and olfactory pathways. However, it is apparent that BoHV-1 only reaches neural tissues via the trigeminal route (Muylkens et al., 2007). Within the trigeminal ganglion (TG), BoHV-1 probably does not replicate further than first order neurons, where latency is established (d\’Offay et al., 1993). Consequently, neurological disease would not be expected to be commonly associated with BoHV-1 infection. Nevertheless, recent reports on the involvement of BoHV-1 in cases of encephalitis in cattle suggest that the virus might be able to replicate in the central nervous system (CNS).

Materials and methods


Although neurological disease associated with BoHV-1 has occasionally been documented (Silva et al., 2007; Rissi et al., 2008), it is considered that BoHV-5 is responsible for typical herpesvirus encephalitis in cattle (Pérez et al. 2002). It is widely accepted that BoHV-1 strains can only replicate focally within the CNS without further spread (Belknap et al., 1994). However, Silva et al. (2007) and Rissi et al. (2008) isolated BoHV-1 from several cases of encephalitis in cattle from southern Brazil. Similar to the findings of the present study, in both reports of natural infections, macroscopic brain lesions were not observed and microscopic lesions were detected in only a few cases.
Virological and histological data from this study demonstrated that both strains of BoHV-1 tested were able to reach and replicate within the nervous system of calves and induce lesions compatible with encephalitis. Silva et al. (2007) suggested that some BoHV-1 isolates might show an increased ability to replicate in neural tissues and cause neurological disease. Moreover, sporadic cases of encephalitis associated with BoHV-1 have been attributed to individual host susceptibility (Muylkens et al., 2007). It is likely that both factors are involved in the development of neurological disease. In our study, we show that respiratory BoHV-1 strains have neuroinvasive potential. Dix et al. (1983) postulated that viral spread is an important property of the virus to induce acute neurological disease.
Slight differences in the sites of replication in neural tissue and virulence of BoHV-1 strains were evident in this study. The amount of infectious virus in the brain does not reflect the progress of disease directly and the neuroinvasive properties of encephalitic strains are not a function of the rate of replication (Bergström and Lycke, 1990). BoHV-1.LA replicated at lower levels in the brain when compared with BoHV-1.Cooper. However, it induced evident microscopic lesions compatible with encephalitis. Similarly, BoHV-5 grows poorly in cell culture, especially when attempting isolation from brain samples (Schudel et al., 1986; Pérez et al., 2002). Nonetheless, it is the causal agent of severe cases of necrotising meningo-encephalitis in calves.

Since the amount of chlorophyll and

Since the amount of chlorophyll, and most likely other potential photosensitizers, is greater in green plant material compared to dry hay, the risk for an animal to develop photosensitization is considered greatest under grazing conditions (Quinn et al., 2014). However, under certain condition, dried plant material can result in the formation of certain phototoxic compounds that lead to disease. This was the case in cattle that were exposed to dried MDV 3100 cost of Cooperia pedunculata in Texas and developed primary photosensitization (Rowe et al., 1987). In another instance, specific conditions had to be present for disease to develop; co-consumption of horse brush (Tetradymia spp.) and sage (Artemisia spp.) appeared to be necessary to result in photosensitization in sheep (Johnson, 1974).


Conflict of interest statement


In addition to stage and substage, the most consistently important prognostic factor for dogs with canine lymphoma (lymphosarcoma) has been immunophenotype (Appelbaum et al., 1984; Greenlee et al., 1990; Rosenberg et al., 1991; Teske et al., 1994; Vail et al., 1996; Ruslander et al., 1997; Baskin et al., 2000; Fournel-Fleury et al., 2002; Ponce et al., 2004). When treated with the same protocol, dogs with T cell, non-indolent lymphoma are less likely to achieve complete remission (CR) and the duration of their remission and overall survival time (OST) are significantly shorter than their counterparts with B cell lymphoma (Teske et al., 1994; Vail et al., 1996; Chun et al., 2000; Curran and Thamm, 2015). T cell lymphomas express higher levels of ATP-binding cassette transporter proteins; which are associated with doxorubicin resistance (Zandvliet et al., 2015).
Nonetheless, current chemotherapy protocols are not routinely tailored for lymphoma immunophenotype (Moore et al., 2001; Garrett et al., 2002; Morrison-Collister et al., 2003; Simon et al., 2006; Daters et al., 2010; Rassnick et al., 2010; Sorenmo et al., 2010). In one study, only 31% of veterinary oncologists used different treatment protocols for dogs with T cell compared to B cell lymphoma (Regan et al., 2013). One retrospective report of 50 dogs with T cell lymphoma treated with L-asparaginase and mechlorethamine, prednisone, procarbazine and vincristine (L-MOPP) found superior response rate and survival compared to historical data for dogs with T cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) based protocols. The CR rate was 78% and the median progression-free survival (PFS) was 189 days (Brodsky et al., 2009).
In another retrospective study of 24 dogs with T cell lymphoma treated with a CHOP-based protocol, a higher proportion of dogs had CR (88%), although the PFS period was shorter at 104 days (Rebhun et al., 2011). A third study found only 10/25 (40%) of 25 dogs with T cell lymphoma treated with CHOP achieved CR for a median PFS of 105 days (Curran and Thamm, 2015). However, analysis of the vincristine, L-asparaginase, cyclophosphamide, lomustine (CCNU), doxorubicin, prednisolone, procarbazine and mechlorethamine (VELCAP-SC) protocol showed no effect of immunophenotype on survival, suggesting a possible benefit for dogs with T cell lymphoma treated with this protocol (Morrison-Collister et al., 2003). Thus, we have continued to use a modified VELCAP-SC protocol (VELCAP-TSC) to treat dogs with non-indolent T cell lymphoma.

Materials and methods


This study represents the largest group of dogs with T cell lymphoma treated with a specific chemotherapy protocol yet reported. The median PFS of 175 days (95% CI, 119–231 days) and the median OST of 237 days (95% CI, 186–288 days) in this study were similar to those reported in two previous studies of canine T cell lymphoma: (1) median PFS of 189 days (95% CI, 99–278 days) (Brodsky et al., 2009);(2) median OST of 270 days (95% CI, 206–333 days) (Brodsky et al., 2009); and (3) median OST of 235 days (95% CI, 164–244 days) (Rebhun et al., 2011). The 1 and 2 year survival rates in the dogs reported in the present study (31% and 20%, respectively) are higher than those in the L-CHOP-based study (1 and 2 year survival rates 14% and 5%, respectively) of Rebhun et al. (2011), but less than the MDV 3100 cost 25% of dogs still alive after 2.6 years in the L-MOPP-based study of Brodsky et al. (2009).

Identical C difficile strains were also detected

Identical C.?difficile strains were also detected in the same animal cyclin dependent kinases for PCR-ribotypes 014, UCL 16U and UCL 36. These results indicate that clonal C.?difficile strains are circulating among the same animal species (including humans), although interspecies transmission was not evident. In a previous study, Kenetsch et?al. (2014) reported transmission between farmers and pigs but the authors did not exclude the possibility of a common environmental source of C.?difficile for both populations. In addition, more than half of the sequenced farmer/pig pairs were not clonal. As in our study, isolates were obtained from subjects localised in different geographical regions and in different environments. It was consequently very unlikely that identical C.?difficile isolates would be found among the different hosts although MLST and MLVA revealed a close relation between them. Furthermore, for PCR-ribotype 078 MLVA showed a higher genetic association between pig and cattle C.?difficile isolates (STRD?≤?6) than between animal and human isolates (STRD?≥?20).
Varshney et?al. (2014) observed significant genotypic and phenotypic differences between meat and human isolates for a variety of PCR-ribotypes, while a few meat isolates (including PCR-ribotype 078) were very similar to human C.?difficile strains. It has been suggested that relatedness between human and animal isolates of PCR-ribotype 078 is a consequence of less natural variability in this type than in other types (Bakker et?al., 2010). However, our results indicate genetic differences that clearly distinguish between human and animal isolates.
As has been previously reported, MLST shows less discriminatory power than MLVA but does establish the C.?difficile genetic lineage (Marsh et?al., 2010). In our study some limitations of the MLVA technique were observed. Three loci, including A6, B7 and CDR5, did not seem to be stable and disappeared from some isolates, recording a null result. Variations in loci total size were also observed for some of the isolates, possibly due to the weak stability of the loci in vitro after several passages which may cause isolates with closely related MLVA profiles to appear non-clonal (Wuyts et?al., 2013). Further studies to investigate the stability of these loci are therefore required. In addition, MLVA provides little insight regarding genetic relatedness. In consequence, it may be useful to combine both methods (MLVA and MLST) in order to resolve phylogenetic diversity (Zaiss et?al., 2009) although the best alternative could be whole genome sequencing, which is generally considered to be the next generation tool to type bacterial strains.
Resistance of C.?difficile to multiple antimicrobials has been described in several previous studies in both humans and animals (Pelaez et?al., 2013; Pirs et?al., 2013). Even though some isolates were resistant to both moxifloxacin and erythromycin or to clindamycin and erythromycin, no association between antimicrobial resistance and toxigenic isolates was observed in our study, echoing the results of previous work by Pituch et?al. (2005). Furthermore, for a given PCR-ribotype, human and animal strains presented a similar susceptibility to the antimicrobials we tested.

This study shows that clonal C.?difficile strains circulate among the same animal species or among human patients, irrespective of the geographic area and the isolation date. The typing methods used also reveal close relationships between isolates of different species, but less genetic similarity among human and animal strains. However, animal and human strains cluster in the same lineage. Our data evidence the need for highly discriminatory genotyping methods, not only to elucidate the possible transmission routes between humans and animals but also to investigate animal-to-animal transmission in herds or cross-contamination at slaughterhouses.

Conflict of interest statement

This study was funded by the Federal Public Service of Health, Food Chain Safety and Environment (contract RF09/6226). The authors would like to thank the public slaughterhouse of Liège-Waremme for permission to sample. Our most sincere thanks go to Cate Chapman and Josh Jones for their support in editing the manuscript. Preliminary results were presented as an abstract at the IAFP European Symposium of Food Safety, Budapest, 7–9 May 2014 and obtained the award in the poster competition.

Other neoplastic diseases are common in

Other neoplastic diseases are common in devils and other marsupials. A carboplatin dosage of 20?mg/kg should be used in any trial for treating potentially susceptible neoplasms in devils and would be considered to be a target dosage for other dasyurids and possibly other marsupials. The toxicity profile of carboplatin in the devil was different than that seen in dogs, cats and humans. The dose limiting toxicity for these species is neutropenia and thrombocytopenia (Moore, 2010; Reed and Chabner, 2011). None of the devils in this study developed neutropenia and only one had a temporary drop in its platelet count, a pattern observed with vincristine (Phalen et?al., 2013). At 26?mg/kg, limiting toxicities to carboplatin treatment in the devil were, instead, severe gastrointestinal toxicity and renal toxicity.
Administration of high-dose carboplatin to human patients with bone marrow support has been associated with non-hematologic toxicities, primarily gastrointestinal and hepatic toxicity (35–41% of patients) and renal toxicity (8% of patients) (Colby et al., 2002). Renal toxicity was more likely in patients with reduced renal excretion, but resolved with supportive care. We observed a similar pattern of toxicity in the three devils treated at the highest dosage level; gastrointestinal toxicity was pronounced and may have led to decreased renal excretion of the drug and progressive renal damage in one animal. It is also possible that tumor metastasis to the kidney may have contributed to clearance rates and nephrotoxicity. However, if this was the case, it was not consistent as most devils with renal metastases did not develop renal failure. In Sulfo-NHS-LC-Biotin to the high degree of toxicity observed in devils treated with 26?mg/kg carboplatin, toxicity was rare and reversible with supportive care in devils treated with the recommended dosage (20?mg/kg).
Based on this study, the recommended dosage for doxorubicin is 1?mg/kg. This dosage is similar to those used in dogs and cats (Moore, 2010). Toxic effects seen in the devils treated at this dosage included mild to moderate anorexia, weight loss, and less commonly neutropenia and all resolved with supportive care. These toxicities are also similar to those reported in dogs and cats (Moore, 2010).
The results of this study demonstrate the complexities of predicting how different drugs will be tolerated by the same species. Both vincristine and doxorubicin are metabolized by the liver, excreted through the bile and their cell concentrations are modulated by the ATP-binding cassette (ABC) protein superfamily (Lage, 2003). However, while devils were able to tolerate dosages of vincristine that are two to six times those used in children, cats, and dogs (Phalen et?al., 2013), Thalassemia were only able to tolerate the same doxorubicin dosage than that used in dogs and cats. We also showed that devils could tolerate dosages (20?mg/kg) of carboplatin that were significantly higher than those tolerated by cats (12?mg/kg) and dogs (10?mg/kg) (Moore, 2010). The mechanism by which devils are able to Sulfo-NHS-LC-Biotin tolerate this higher dosage of carboplatin is not known. Cellular concentrations of carboplatin are not impacted by the ABC protein superfamily and carboplatin is not metabolized in the liver (Lage, 2003). Instead, carboplatin is largely excreted by the kidney (Reed and Chabner, 2011). A pharmacokinetic study will be needed to determine the role of pharmacokinetics and pharmacodynamics in carboplatin tolerance.


Conflict of interest statement

This trial was funded through a Tasmanian Government Project grant and completed as a joint collaboration between the Wildlife Health and Conservation Centre at the University of Sydney, Veterinary Oncology Consultants, and the Tasmanian Department of Primary Industries and Water. Support was provided by Carmel Pharma (donation of PhaSeal products), Pfizer Animal Health Australia (donation of maropitant) and Hills Pet Nutrition Pty Ltd (donation of Hill\’s a/d). We would also thank the devil keepers for the care and attention to the animals used in this study.

Diazepam is not soluble in water

Diazepam is not soluble in water, and is available commercially either in propylene glycol or as a lipid emulsion. Midazolam is water soluble, short-acting and is, in humans, at least two to four times as potent as diazepam (Reves et al. 1985; Nuotto et al. 1992). In dogs, IV midazolam at doses ranging from 0.2 to 0.5 mg kg−1 is characterized by elimination half-lives (t1/2β) of 63.3 ± 28.5 to 121 ± 26 minutes (Court & Creenblatt 1992; Eagleson et al. 2012; Schwartz et al. 2013). For IV diazepam at a dose of 0.5 mg kg−1 a FRAX597 of 2.07 ± 0.15 hours was found (Platt et al. 2000); for 2 mg kg−1 the t1/2β was found to be 2.26 ± 0.41 hours in the same species (Probst et al. 2013). Although little information on equine benzodiazepine pharmocokinetics has been published, midazolam\’s elimination half-life in horses has been shown to be considerably less than that of diazepam. Hubbell et al. (2013) report a median t1/2β for midazolam of 3.6 hours (range 2.0–4.1) after an IV dose of 0.05 mg kg−1 in conscious healthy horses. Muir et al. (1982) found a median t1/2β of 6.9–21.6 hours for diazepam after IV doses ranging from 0.05 to 0.4 mg kg−1. In addition, in foals aged 4, 21, 42 and 84 days, diazepam administered at 0.25 mg kg−1 led to terminal half-lives of 4, 3.5, 5 and 3.5 hours, respectively (Norman et al. 1997).
Compared with diazepam, midazolam has a high benzodiazepine receptor-binding affinity and high lipophilicity at physiological pH (Reves et al. 1985) and consequently lower doses could theoretically be administered.

Materials and methods
The study was approved by the Research Ethics Committee of the Animal Health Trust, Newmarket (UK), and performed by two anaesthetists, of whom one was responsible for preparation and administration of medications and one who was unaware of treatment and undertook all monitoring, measuring and scoring as per the protocol. Scoring was performed according to simple descriptive scales modified from Klöppel & Leece (2011) with 1 representing the best score (Appendix S1).
Twenty healthy, 1 year old, entire male Welsh section A ponies, American Society of Anesthesiologists (ASA) classification I undergoing castration under field conditions were studied. Mean bodyweight ± SD was 156 ± 12 kg. All ponies were kept in a herd and were not used to handling; therefore no blood was sampled prior to the study and physical examination was limited to auscultation of heart, lungs and abdomen immediately before sedation. Ponies were kept on straw with free access to water before the start of the study. Each pony was restrained individually in a crush and sedated with detomidine hydrochloride (Domosedan; Pfizer Animal Health, UK) 20 μg kg−1 IV. The skin over the left jugular vein was then clipped, surgically prepared and locally infiltrated with mepivacaine hydrochloride (Intra-Epicaine; Dechra Veterinary Products, UK) after which a 16-gauge IV catheter (Intraflon 2; Vygon Ltd, UK) was placed and glued to the skin with cyanoacrylate. Phenylbutazone (Equipalazone; Dechra Veterinary Products) 4.4 mg kg−1 was injected IV. Ponies were guided out of the crush onto straw bedding for induction of anaesthesia; quality of sedation was assessed.
According to random allocation by means of individually closed envelopes, anaesthesia was induced with ketamine (Narketan; Vetoquinol Ltd, UK) 2.2 mg kg−1 mixed in the syringe with either midazolam (Hypnovel; Roche Products Ltd, UK) 0.06 mg kg−1 (group M) or diazepam (Diazepam; Wockhardt UK Ltd, UK) 0.06 mg kg−1 (group D). Both diazepam and midazolam solutions were clear and colourless, containing 5 mg mL−1, therefore identification of test drug was not possible by visual inspection of the syringe.
Quality of induction was scored and after lateral recumbency had been achieved, endotracheal intubation was performed and scored. The ponies spontaneously ventilated on ambient air. Butorphanol tartrate (Torbugesic; Pfizer Animal Health) 0.05 mg kg−1 was administered IV, penicillin-streptomycin (Depocillin; Intervet Schering-Plough, UK) 12 mg kg−1 intramuscularly and tetanus antitoxin (Tetanus Antitoxin; Intervet Schering-Plough) 7500 IU in total subcutaneously. Pulse rate (PR), respiratory rate (fR), palpebral reflex, eye position and movement, lacrimation, mucous membrane colour and any spontaneous movements were recorded every 5 minutes. Arterial oxygen haemoglobin saturation (SpO2) was measured using a pulse oximeter placed on the tongue and indirect arterial blood pressure (ABP), by means of oscillometry with an appropriately sized cuff on the tail, were recorded at the same time points (Kontron Instruments Ltd., Watford, UK). If anaesthesia was deemed insufficient, or if spontaneous movement occurred, incremental ketamine (0.2 mg kg−1 IV) was administered; the time of first dose and the total amount administered to each animal were documented.

br Discussion A ligated loop study was selected for

A ligated loop study was selected for this experiment as it removes many variables encountered in alternative experimental designs. These include variation in initial Campylobacter colonization levels, gastrointestinal transit times and influences of microbiota encountered en route to the caeca. This approach should greatly reduce the number of animals required to obtain significant results as it removes inter-animal variation. This is in keeping with the principle of replacement, refinement and reduction of animals in research (Russell & Burch 1959). The authors are unaware of any published reports describing a monitored, controlled anaesthesia of this duration in chickens. Several older texts describe ligated loop studies, but the anaesthesia is often not described in detail. We report these results to demonstrate that long-term anaesthesia for this caecal ligation model is viable, so that others may use it in future.
Once anaesthesia was induced, intermittent positive pressure ventilation was initiated with no resistance or bucking of the ventilator. There was therefore no requirement for neuromuscular blockade. Butorphanol was included in the protocol as it has been demonstrated to have an isoflurane-sparing effect in Psittaciformes (Curro et al. 1994). The pharmacokinetics of butorphanol have recently been described in broilers by Singh et al. (2011), informing our selected dose of 2 mg kg−1 every 2 hours.
Pulse oximetry for the estimation of haemoglobin oxygen saturation has been widely considered as unreliable in avian species (Edling 2006). The equipment is calibrated for mammalian, not avian, haemoglobin and tissues and tends to underestimate the haemoglobin saturation in ascorbic acid (Schmitt et al. 1998). The Viamed pulse oximeter used in this study provided a very consistent trace and gave an audible alarm when the trace was lost. Validating SpO2 data was not possible in this pilot study, but this could be performed in future studies. The pulse oximeter probe from the older Kontron monitor (Minimon 7138B) provided no trace or SpO2 reading.
Bird 6, which died after 285 minutes of anaesthesia, was the heaviest and most muscled of the chickens anaesthetized. The ‘sudden death’ syndrome (SDS) of broiler chickens tends to affect faster-growing birds and although the aetiology is poorly defined it may be associated with cardiac arrhythmias (Crespo & Shivaprasad 2013). Given that this bird may have had the lowest cardiorespiratory reserve capacity within our cohort, we believe SDS is a possibility. No gross lesions were apparent at post-mortem, which can be consistent with SDS.
Clinical texts frequently emphasize the requirement for speed, as avian patients requiring anaesthesia for procedures are rarely healthy (Edling 2006). Long-term, stable anaesthesia does appear to be possible in healthy chickens. As these were terminally anaesthetized for ethical reasons, we have no data on recovery and survival after the procedures. The anticipated problems of hypothermia, hypoventilation and regurgitation were avoided or managed, and monitored parameters were within acceptable physiological limits. Studies such as that by Fedde et al. (1998) have demonstrated the HR in conscious broiler chickens to be in the region of 360 beats minute−1.
The duration of preoperative fasting in avian patients is controversial, with the aim being to balance the avoidance of regurgitation during induction with the maintenance of adequate energy reserves for a long procedure (Edling 2006). A small degree of regurgitation was noted mid-procedure in Bird 6, which had the shortest feed withdrawal time of 2 hours; however, the crop was palpably empty even when the feed was removed. The material was removed with cotton swabs, and was considered unrelated to the anaesthetic death as no material was noted in the trachea at post-mortem examination.
As described elsewhere in the literature (Edling 2006), air sacs were ruptured during this procedure. Isoflurane pollution of the environment is inevitable, and therefore adequate ventilation of the operative area is essential and charcoal-filtered surgical masks should be considered.

It should be noted that because

It should be noted that because there is some uncertainty regarding the actual values of the allometric exponents, and because the values of the exponents may vary with the conditions under study, analysis of covariance may be a preferable approach to traditional indexing to account for the effect of body size on cardiopulmonary measurements (Packard & Boardman 1988, 1999). This approach has been utilized to account for the degree of interrelatedness between ionomycin in the development of phylogenetically informed allometry (Garland et al. 2005).
In conclusion, we suggest that when cardiovascular and respiratory variables are indexed to account for the effect of body size, this indexing should: 1) use body mass raised to the appropriate exponent according to the allometric scaling literature; 2) use different exponents for inter- versus intraspecific comparisons; and 3) ensure that variables which scale intraspecifically with metabolic rate (M2/3) are indexed for the effect of body size by dividing the measurements by M2/3 rather than by BSA.

Dogs frequently undergo general anesthesia for a variety of minimally invasive procedures and inhalation anesthesia is the most commonly used method of general anesthesia for these procedures. Inhalation anesthesia requires specialized equipment for the delivery of oxygen and anesthetic agent as well as a means to eliminate exhaled CO2 and anesthetic. Injectable anesthetic agents, such as propofol or ketamine, offer an alternative option for procedures of short duration or when inhalation anesthesia may not be possible or practical, such as bronchoscopy, tracheoscopy, laryngeal examination, or magnetic resonance imaging. Propofol will provide rapid and smooth induction and maintenance of anesthesia, however, it causes dose dependent respiratory depression and hypotension (Pagel & Warltier 1993; Nagashima et al. 1999, 2000; Aguiar et al. 2001). Ketamine can also be used for the induction and maintenance of anesthesia. Ketamine is unique among anesthetics in that it maintains or increases cardiac output (CO) as a result of increased sympathetic efferent activity (Wong & Jenkins 1974), except under conditions of catecholamine depletion where ketamine may act as a direct myocardial depressant (Pagel et al. 1992). Ketamine can also be associated with muscle rigidity, convulsions, and violent recoveries (Haskins et al. 1985), thus it is often used in conjunction with a benzodiazepine.
A study investigating the combination of propofol with ketamine on the cardiopulmonary changes in dogs during induction of anesthesia, ketamine combined with propofol allowed a dose reduction of propofol and resulted in better maintenance of mean arterial pressure (MAP) with increased CO and oxygen delivery compared to propofol alone (Henao-Guerrero & Riccó 2014). Administration of a ketamine infusion to dogs during isoflurane anesthesia permitted a reduction in isoflurane concentration, resulting in improved hemodynamics, ventilation, and oxygenation (Boscan et al. 2005). The addition of ketamine to propofol for induction and maintenance of injectable anesthesia may partly offset the cardiovascular depression induced by administration of propofol. In addition, any propofol dose reducti### afforded by the co-administration of ketamine may have the potential to reduce the dose dependent respiratory depression observed with a continuous infusion of propofol alone in dogs.
The purpose of this investigation was to compare a ketamine-propofol combination to propofol alone for induction and constant rate infusion (CRI) maintenance for total intravenous anesthesia (TIVA) in unpremedicated healthy dogs. The hypotheses were that ketamine added to propofol in a 1:1 mg mL−1 mixture used as TIVA would 1) provide improved hemodynamic and respiratory function during a 60 minute anesthetic period compared to TIVA with propofol alone, 2) would not result in adverse recovery quality, and 3) would reduce the dose of propofol needed for both induction and maintenance of anesthesia.

br Introduction Total intravenous IV anesthetic

Total intravenous (IV) anesthetic techniques are commonly used to anesthetize horses in the field for short procedures, such as castration. sphingosine 1-phosphate receptor modulator A popular technique involves the use of a xylazine, ketamine and guaifenesin (XKG) infusion to maintain anesthesia after appropriate induction (Young et al. 1993; Hubbell et al. 2010). Although blood pressure is usually well maintained under this and other similar injectable protocols (Young et al. 1993; McMurphy et al. 2002), changes in arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) are commonly seen (Muir et al. 1978; Taylor et al. 1998; Braun et al. 2009).
Decreases in PaO2 indicate poor oxygenation and, during general anesthesia in healthy horses, can be attributed to hypoventilation, inadequate inspired oxygen, increased ventilation-perfusion mismatch and intrapulmonary shunts (Braun et al. 2009). Hypoxemia may develop, which can lead to cardiovascular complications intraoperatively, or to neurological damage, myopathy, and hepatic and renal failure or dysfunction postoperatively (Steffey et al. 1992). In field settings, hypoxemia may go undetected as pulse oximetry and blood gas analysis may not be available and the visual identification of cyanosis is unreliable (Comroe & Botelho 1947). At present, oxygen therapy in the field requires the use of portable compressed oxygen cylinders. There are ongoing costs associated with the use of cylinders and practitioners may be reluctant to travel with oxygen cylinders because of the risks associated with the transportation of compressed gas. A potential alternative is a portable battery-operated oxygen concentrator, which is safe to handle and requires minimal maintenance. The oxygen concentrators are commonly used in humans for the provision of oxygen at home or during air travel, in military applications and in remote medical facilities in the developing world (Friesen 1992; Shrestha et al. 2002). They have also been shown to be effective in the treatment of hypoxemia during injectable anesthesia in some wildlife sphingosine 1-phosphate receptor modulator (Fahlman et al. 2012).
Portable oxygen concentrators are capable of producing oxygen concentrations of >90% through the use of molecular sieve technology. Two modes of delivery involving either continuous or pulsed-flow delivery are available (Friesen 1992). Continuous flow can be delivered at a maximum of 3 L minute−1 (SeQual Technologies Inc 2010). The pulsed-flow mode reduces oxygen waste during expiration and allows a significant increase in battery-powered operating time. This is achieved through the delivery of an oxygen bolus at the beginning of each inspiratory effort, which is controlled by the demand valve. Portable oxygen concentrators may prove to be an effective and safe means to treat or prevent hypoxemia during field anesthesia in horses. To the authors’ knowledge, the use of these devices has not been evaluated in equine anesthesia. The purpose of this study was to determine if the oxygenation of horses anesthetized with a XKG infusion during a field castration procedure could be improved by the pulsed-flow delivery of oxygen from a battery-powered portable oxygen concentrator. The investigation was based on the hypothesis that the administration of oxygen by pulsed-dose flow via an oxygen concentrator would result in higher PaO2 values in the treatment group. In the control group, without supplemental oxygen, it was hypothesized that there would be no change in PaO2.

Materials and methods
Approval for animal use in this project was granted by the Animal Care and Use Committee of the University of Calgary (AC12-0032). Fifteen yearling colts were anesthetized under field conditions for a castration teaching laboratory at the University of Calgary Faculty of Veterinary Medicine. The castrations were performed in a covered arena bedded with rubber pellets. Procedures in the control group of the study were performed during a teaching laboratory in March 2012; procedures in the treatment group were performed in March 2013. All horses were deemed by physical examination to be healthy and free from cardiovascular or respiratory disease prior to anesthesia. Horses were housed in group pens and fasted the evening prior to the procedure. Water was available ad libitum until the time of the procedure. Students, assisted by experienced veterinary surgeons, performed castrations using both modified open- and closed-techniques, as previously described (Kramer 2006).

The incidence and the severity of

The incidence and the severity of nausea were also reduced when BUT was co-administered with DEX in the present study. However, protocol C failed to induce a significant reduction in the incidence and the severity of nausea compared with the control protocols (A and E). This result may be attributed to the lower dose (0.1 mg kg−1) of BUT in protocol C compared with that (0.2 mg kg−1) in protocols A and E.
The doses of DEX that were used in the present study (20 and 25 μg kg−1) were chosen on the basis that no invasive procedures were performed in the cats. However, these doses are enough to induce emesis (Santos et al. 2010) and are commonly used in clinical practice for cats as they provide adequate sedation and analgesia when combined with opioids (Slingsby & Taylor 2008).
The present study has two limitations. Incidents of emesis and nausea were recorded during an 8-minute period; after this buy MLN 9708 atipamezol was administered. The incidence of emesis after that time could not be recorded. In two other similar studies, the first emetic event was recorded between 0 and 13 minutes (Santos et al. 2011), and between 2 and 10 minutes (Slingsby & Taylor 2008) after DEX administration. Nevertheless, in the present study 20 of the 22 (91%) episodes of emesis occurred within the first 5 minutes after drug injection. One more episode of emesis occurred between the 6th and the 7th minute and another one occurred just before the end of the 8-minute period after the injection. Based on that result, we believe that the majority of episodes of emesis were recorded within the 8-minute period. Another limitation of the present study may be the use of a sedation scoring system previously designed for dogs. However, we are not aware of a sedation scoring system specifically designed for use in cats. Most of the sedation scoring systems previously used for cats (Ansah et al. 1998; Santos et al. 2010, 2011; Nagore et al. 2013) are based on the same criteria that were used in the present study.
In conclusion, based on the results of the present study, 0.1 or 0.2 mg kg−1 BUT can be used in cats in order to prevent DEX-induced emesis. In addition, BUT at a dose of 0.2 mg kg−1 can reduce the incidence and the severity of nausea caused by DEX when administered in the doses used in the present study. It seems that the combination of BUT and DEX can be very useful not only in cases were emesis could possibly result in serious complications, but also to provide comfort and well-being in cats sedated for minor procedures.

Measuring cardiac output (
t) in calves is not normally performed in clinical practice because it is costly and invasive. Monitoring often relies on basic clinical assessment, as it does in paediatric practice, although clinical estimation of
t in the latter has been shown to be inadequate (Tibby et al. 1997a; Egan et al. 2005). Therefore
t is measured in calves in research settings to assess the cardiovascular effects of drugs (Bleul et al. 2010; Offinger et al. 2012; Araújo et al. 2014) or to evaluate clinical monitoring techniques and consider their validity in the prediction of
t (Constable et al. 1998). Calves are often used as a cardiovascular model for humans in research (i.e. for artificial hearts because of similarities in size and thoracic anatomy) and require
t monitoring (Rokitansky et al. 1990; Takaseya et al. 2012).
Pulmonary artery thermodilution (PATD) as a technique to measure
t has been evaluated in the unsedated calf using the Fick method as a reference method (Amory et al. 1991). Both PATD and the Fick method require the placement of a pulmonary artery catheter (PAC), which has been found to lead to an unusually high prevalence of ventricular dysrhythmias and pulmonary hypertension in cattle compared with other species (Reeves & Leathers 1964; Amory et al. 1992). In human patients PAC placement is associated with increased morbidity and mortality (Harvey et al. 2005; Frazier & Skinner 2008).

In group P arterial pH was

In group P, arterial pH was significantly decreased and PaCO2 increased after 5 minutes of anesthesia (p = 0.001 and p = 0.034, respectively) (Table 3). PaCO2 in EID was unchanged after induction of anesthesia compared with baseline but did not differ from values in P and PD at 5 minutes. There were no significant differences over time in PaO2 and HCO3− in any group (Table 3), but in PD at minute, PaO2 was lower and had a wide SD and SpO2 was < 90%, both indicating decreased oxygenation. In EID, BE displayed a slight but significant decrease from baseline at minute (p = 0.046) but did not differ significantly at 5 minutes. The PA–aO2 gradient was significantly higher after induction of anesthesia compared with baseline in all groups (p < 0.05) and did not differ significantly among the groups. Adverse events, noted throughout the procedure, were SB 239063 (n = 3) and paddling (n = 1) in group P, apnea (n = 2), decreased PR (n = 7), regurgitation (n = 1) and paddling (n = 1) in group PD, and apnea (n = 1), decreased PR (n = 6) and vocalization (n = 1) in group EID. All dogs were anesthetized for the 5 minute measurement. Five dogs in PD and one dog in EID were anesthetized at 10 minutes. All dogs recovered from anesthesia and none died.

The quality of induction of anesthesia was good in the majority of dogs in this study, with few adverse reactions, which is in agreement with the findings of other investigators in studies using propofol, alfaxalone and etomidate (Sams et al. 2008; Maney et al. 2013; Raszplewicz et al. 2013). Incidences of post-induction apnea were similar among the three groups. The mean time from extubation to achieving a sternal position, time from sternal recumbency to standing, and total recovery time were shortest in group EID. IV EI anesthesia has the characteristics of both IV anesthesia and inhalation anesthesia (Yang et al. 2006), and because the primary elimination route following IV infusion of EI is via the lungs (Fan et al. 2014), the speed of recovery from EI will be faster than that after propofol. Yang et al. (2006) reported that IV injection of 8% EI resulted in a lower minimum alveolar concentration (MAC) and faster induction of anesthesia in dogs compared with inhaled isoflurane, without local redness or swelling at the infusion site, or mortality.
In the present study, group EID showed a significant difference in SAP at 5 minutes and a progressive non-significant decrease in MAP. Inhaled isoflurane was previously reported to be associated with a dose-dependent decrease in blood pressure (Eger 1984; Tanaka et al. 1996). The significant decreases in PR in both dexmedetomidine groups (44% in PD and 32% in EID) were expected as a2-agonists have central sympatholytic effects, but do not affect vagal efferent activity (Murrell & Hellebrekers 2005). Mean SpO2 was decreased to < 90% immediately after propofol administration in PD, which suggests that some dogs may have had decreased oxygenation. Previous studies reported respiratory depression and apnea to be the most consistent and important side effects in animals receiving IV propofol (Ilkiw et al. 1992; Muir & Gadawski 1998). Bell et al. (2011) reported that dexmedetomidine influences fR when administered as a pre-anesthetic medication. However, PaO2 values were not as low in groups P and EID and therefore the decreased oxygenation may not have been associated with apnea in this SB 239063 study.
In both the PD and EID groups, fR was decreased significantly after premedication and during anesthesia, which is in accordance with previous findings (Bell et al. 2011). However, the greater increase in PaCO2 in group PD compared with EID suggests that ventilation was decreased to a greater extent during PD anesthesia. Dogs in group EID developed a mild metabolic acidosis after induction of anesthesia, which did not occur in groups P or PD, although BE values did not differ between groups EID and P at 5 minutes. Further investigations are required to uncover the mechanism leading to metabolic acidosis in EID. In the present study, PA–aO2 increased in all groups after induction, but was maintained at > 10 mmHg (1.3 kPa) at 5 minutes.