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1.
Schweiz Arch Tierheilkd ; 163(6): 431-436, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34097637

RESUMO

INTRODUCTION: A mixed breed dog was anesthetized for diagnostic myelography to investigate acute onset neck pain. Instead of contrast medium, 444 µg/kg medetomidine were inadvertently injected into the cerebromedullaris cisterna owing to a human error. Severe bradycardia, undetectable peripheral pulse, respiratory arrest and loss of pupillary, palpebral and corneal reflexes were observed immediately after injection. Profound hypothermia developed and esophageal temperature, measured 20 minutes after medetomidine injection, was 33 °C. Atipamezole at 1 mg/kg im was administered, followed by a second dose of 0,5 mg/kg iv 20 minutes thereafter. In the meantime, cardiorespiratory parameters and body temperature were monitored, and supportive care that included manually assisted pulmonary ventilation, active warming, and administration of 5 µg/kg/min dopamine was initiated. The dog's clinical condition improved within one hour from the beginning of supportive care, at which time ocular reflexes and swallowing returned, spontaneous ventilation was deemed as adequate and the trachea could be extubated. The dog was discharged in good clinical conditions five days later. Human error and distraction led to a potentially life-threatening complication in the dog of this report and could have possibly been prevented with the use of checklists and with a clearer definition of roles and responsibilities of the personnel involved prior to commencing the clinical procedure. Profound cardiovascular, respiratory, and thermoregulatory depression caused by intracisternal injection of medetomidine responded to parenteral administration of its antagonist and supportive care.


Assuntos
Imidazóis/administração & dosagem , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Erros Médicos/veterinária , Mielografia/veterinária , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Cães , Hipnóticos e Sedativos/administração & dosagem , Resultado do Tratamento
2.
Eur J Neurosci ; 54(3): 4906-4919, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34137097

RESUMO

Medetomidine and isoflurane are commonly used for general anaesthesia in fMRI studies, but they alter cerebral blood flow (CBF) regulation and neurovascular coupling (NVC). In addition, medetomidine induces hypoinsulinemia and hyperglycaemia, which also alter CBF regulation and NVC. Furthermore, sudden changes in arterial pressure induced by noxious stimulation may affect NVC differently under medetomidine and isoflurane anaesthesia, considering their different effects on vascular functions. The first objective of this study was to compare NVC under medetomidine and isoflurane anaesthesia during noxious stimulation. The second objective was to examine whether fasting may improve NVC by reducing medetomidine-induced hyperglycaemia. In male Wister rats, noxious electrical stimulation was applied to the sciatic nerve in fasted or non-fasted animals. CBF and local field potentials (LFP) were recorded in the somatosensory cortex to assess NVC (CBF/LFP ratio). The CBF/LFP ratio was increased by medetomidine compared with isoflurane (p = 0.004), but this effect was abolished by fasting (p = 0.8). Accordingly, medetomidine produced a threefold increase in blood glucose (p < 0.001), but this effect was also abolished by fasting (p = 0.3). This indicates that isoflurane and medetomidine anaesthesia alter NVC differently, but the undesirable glucose dependent effects of medetomidine on NVC can be prevented by fasting.


Assuntos
Hiperglicemia , Isoflurano , Acoplamento Neurovascular , Animais , Jejum , Isoflurano/toxicidade , Masculino , Medetomidina , Ratos , Córtex Somatossensorial
3.
J S Afr Vet Assoc ; 92(0): e1-e5, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34082540

RESUMO

Anaesthesia in pinnipeds is considered a much higher risk than in most terrestrial mammals because of their frequent proximity to water and physiological and anatomical adaptations related to diving, which also influence their anaesthesia management. Anaesthetising and immobilising entangled seals does not allow for selection of animals that are at a safe distance from the water's edge. Medetomidine-midazolam-butorphanol (MMB) sedation was trialled on eight entangled Cape fur seals (CFS) (Arctocephalus pusillus pusillus) to determine if it was safe to use on animals that entered the water post-darting. The MMB was given at an estimated dose of 0.03 mg/kg, 0.2 mg/kg and 0.2 mg/kg, respectively, via remote darting. Sedation was reversed with intramuscular atipamezole (0.15 mg/kg) and naltrexone (0.4 mg/kg) to antagonise the effects of medetomidine and butorphanol, respectively. Moderate sedation was achieved in six animals. Six of the animals entered the water after being darted. There was a single mortality and a single animal that was too lightly sedated for capture. The preliminary results indicate that MMB produces suitable sedation for disentanglement of CFS. Additionally, MMB might be suitable for application to field-based biological research.


Assuntos
Butorfanol/farmacologia , Otárias , Medetomidina/farmacologia , Midazolam/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Animais , Sedação Consciente , Combinação de Medicamentos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Medetomidina/administração & dosagem , Midazolam/administração & dosagem , Naltrexona/administração & dosagem , Naltrexona/farmacologia , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/farmacologia
4.
J Zoo Wildl Med ; 52(2): 445-452, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130386

RESUMO

Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO2, oxygen saturation (SpO2), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO2, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia.


Assuntos
Injeções Intramusculares/veterinária , Medetomidina/farmacologia , Pan troglodytes , Tiletamina/farmacologia , Zolazepam/farmacologia , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Combinação de Medicamentos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares/métodos , Masculino , Medetomidina/administração & dosagem , Midazolam/farmacologia , Tiletamina/administração & dosagem , Zolazepam/administração & dosagem
5.
J Zoo Wildl Med ; 52(2): 715-720, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130416

RESUMO

Fifty-three free-ranging moose (Alces americanus) cows were darted from a helicopter with 3-4 ml of a premix combination of butorphanol (27.3 mg/ml), azaperone (9.1 mg/ml), and medetomidine (10.9 mg/ml; BAM), equivalent to estimated dosages of: butorphanol 0.26 ± 0.08 (mean ± SD) mg/kg, azaperone 0.09 ± 0.03 mg/kg, and medetomidine 0.11 ± 0.03 mg/kg. After a mean chase time (from sighting to darting) of 6.1 ± 5.5 min, the mean induction time (from darting to recumbency) was 8.3 ± 2.6 min. This combination provided a safe and reliable sedation for minor procedures that lasted 30-60 min. Heart rate (50.4 ± 7.0 beats/min), respiratory rate (21.3 ± 11.1 breaths/minute), ETCO2 via nasal canula (43.2 ± 7.0 mmHg), and rectal temperature (38.5°C ± 0.7°C) mostly remained at expected values for wild cervid and bovid species anesthetized with this drug combination. SpO2 (90.0% ± 3.7%) was suggestive of moderate hypoxemia despite intranasal oxygen supplementation (1 L per 100 kg/min). The recovery time to standing was 6.7 ± 3.8 min after reversal with IM naltrexone (3 mg/mg butorphanol) and atipamezole (5 mg/mg medetomidine). Despite a larger volume to inject, this protocol offers an alternative to highly potent opioids, and should be considered for practical or staff safety reasons. On the basis of the results of this study, the use of 4 ml of BAM is considered a safe and effective protocol for immobilization of cow moose under comparable settings.


Assuntos
Azaperona/farmacologia , Butorfanol/farmacologia , Cervos , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestesia/veterinária , Animais , Animais Selvagens , Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Medetomidina/administração & dosagem
6.
BMC Vet Res ; 17(1): 201, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049559

RESUMO

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.


Assuntos
Butorfanol/farmacologia , Galinhas , Monitores de Consciência/veterinária , Isoflurano/farmacologia , Medetomidina/farmacologia , Sevoflurano/farmacologia , Anestésicos Combinados/farmacologia , Animais , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Estudos Prospectivos
7.
PLoS Biol ; 19(4): e3001146, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33793545

RESUMO

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.


Assuntos
Anestésicos/efeitos adversos , Hipocampo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Coluna Vertebral/efeitos dos fármacos , Anestesia/efeitos adversos , Anestésicos/farmacologia , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Fentanila/efeitos adversos , Fentanila/farmacologia , Hipocampo/citologia , Hipocampo/fisiologia , Isoflurano/efeitos adversos , Isoflurano/farmacologia , Ketamina/efeitos adversos , Ketamina/farmacologia , Masculino , Medetomidina/efeitos adversos , Medetomidina/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Midazolam/efeitos adversos , Midazolam/farmacologia , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Coluna Vertebral/fisiologia , Xilazina/efeitos adversos , Xilazina/farmacologia
8.
J Zoo Wildl Med ; 52(1): 287-294, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827187

RESUMO

This study investigated the use of a fixed-dose combination of 30 mg/ml butorphanol, 12 mg/ml azaperone, and 12 mg/ml medetomidine for the standing sedation of captive African elephants (Loxodonta africana). In total, seven females (mean age 19.6 yr; range 6-31 yr) and six males (mean age 33.5 yr; range 9-35 yr) were sedated. The estimated dose was 0.0005 ± 0.0001 ml/kg and 0.006 ± 0.001 ml/cm shoulder height, which resulted in a dose of 0.016 ± 0.002 mg/kg or 0.19 ± 0.04 mg/cm shoulder height butorphanol, 0.006 ± 0.0008 mg/ kg or 0.076 ± 0.015 mg/cm shoulder height azaperone, and 0.006 ± 0.0008 mg/kg or 0.076 ± 0.015 mg/cm medetomidine. First signs of sedation were observed within 3-10 min (mean 6 ± 2 min) after darting, and monitoring of the animals started on average at 24 ± 9 min after darting. No bradycardia was observed in any of the elephants (mean heart rate 40.0 ± 6.55 beats/min), although all the animals were mildly hypotensive (mean blood pressure 118.5/86 [94.5]). Rectal temperatures fell within acceptable ranges, and respiratory parameters were stable in all the animals throughout sedation and fell within the standard ranges reported for conscious, standing elephants. Only one elephant had clinically significant hypoxemia characterized by a partial pressure of oxygen (PaO2) < 60 mm Hg. This elephant was also hypercapnic (PaCO2 > 50 mm Hg), although pH and peripheral capillary oxygen saturation fell within acceptable ranges. None of the elephants reacted to moderately painful stimuli while sedated. The combination was reversed with intramuscular injections of naltrexone (1 mg for every 1 mg butorphanol) and atipamezole (5 mg for every 1 mg medetomidine). Recovery was smooth and calm in all the animals. Time from injection of the reversals until the first signs of recovery was 4.6 ± 2.01 min (range 1-8 min).


Assuntos
Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Fármacos do Sistema Nervoso Central/administração & dosagem , Sedação Consciente/veterinária , Elefantes/fisiologia , Medetomidina/administração & dosagem , Analgésicos Opioides/administração & dosagem , Animais , Combinação de Medicamentos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Masculino , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem
9.
J Vet Med Sci ; 83(4): 643-647, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33583912

RESUMO

The purpose of this study was to assess the cardiorespiratory and behavioral responses to the combination of medetomidine and tramadol (M-T) or butorphanol (M-B) in standing laparoscopic ovariectomy in horses. One ovary was removed under M-T and the contralateral ovary was removed under M-B with at least 4 weeks between operations at random. Horses were sedated using intravenous medetomidine (5 µg/kg) followed by tramadol (1 mg/kg) or butorphanol (10 µg/kg) after 5 min. Sedation was maintained through the repeated injection of medetomidine (1 µg/kg) and tramadol (0.4 mg/kg) or medetomidine (1 µg/kg) and butorphanol (4 µg/kg) every 15 min. Cardiorespiratory function and behavioral responses, including, sedation, ataxia, and analgesia, were assessed during the surgery. There were no significant differences in cardiorespiratory values and sedation and analgesia scores between M-T and M-B. Ataxia scores were significantly lower in M-T than in M-B. This result suggests that M-T could maintain smooth and stable standing surgery with minimal cardiorespiratory changes in horses.


Assuntos
Laparoscopia , Tramadol , Analgésicos Opioides/farmacologia , Animais , Butorfanol/farmacologia , Feminino , Frequência Cardíaca , Cavalos , Hipnóticos e Sedativos/farmacologia , Laparoscopia/veterinária , Medetomidina/farmacologia , Ovariectomia/veterinária
10.
J Chem Inf Model ; 61(1): 481-492, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33404240

RESUMO

The α2a adrenoceptor is a medically relevant subtype of the G protein-coupled receptor family. Unfortunately, high-throughput techniques aimed at producing novel drug leads for this receptor have been largely unsuccessful because of the complex pharmacology of adrenergic receptors. As such, cutting-edge in silico ligand- and structure-based assessment and de novo deep learning methods are well positioned to provide new insights into protein-ligand interactions and potential active compounds. In this work, we (i) collect a dataset of α2a adrenoceptor agonists and provide it as a resource for the drug design community; (ii) use the dataset as a basis to generate candidate-active structures via deep learning; and (iii) apply computational ligand- and structure-based analysis techniques to gain new insights into α2a adrenoceptor agonists and assess the quality of the computer-generated compounds. We further describe how such assessment techniques can be applied to putative chemical probes with a case study involving proposed medetomidine-based probes.


Assuntos
Aprendizado Profundo , Receptores Adrenérgicos alfa 2 , Ligantes , Medetomidina
11.
J Zoo Wildl Med ; 51(4): 825-833, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480562

RESUMO

Alfaxalone has been successfully used intramuscularly (im) combined with medetomidine and azaperone for immobilization of small ungulates. An experimental 40 mg/ml alfaxalone solution (RD0387) was recently formulated for reduced injection volume. The objective of this study was to assess the efficacy and cardiopulmonary effects of high-concentration alfaxalone combined with medetomidine and azaperone for the intramuscular immobilization of captive Rocky Mountain elk (Cervus elaphus nelsoni). Seven adult female elk were used in a crossover design in which they were administered alfaxalone 1 mg/kg, medetomidine 0.05 mg/kg, and azaperone 0.1 mg/kg or alfaxalone 0.5 mg/kg, medetomidine 0.1 mg/kg, and azaperone 0.1 mg/kg im approximately 3 wk apart. Drugs were delivered to each elk in a chute by hand injection. Once recumbent, elk were placed in sternal recumbency for a period of 30 min, during which time level of sedation, response to minor procedures, heart rate, respiratory rate, rectal temperature, oxygen saturation, and direct arterial blood pressures were recorded every 5 min. Arterial blood gases were performed every 15 min. At 30 min, elk were administered atipamezole 0.25 or 0.5 mg/kg im and recovery quality and times were recorded. Statistical comparisons were made by t test, Wilcoxon signed rank test, and repeated measures analysis (significance level P < 0.05). Both drug combinations provided effective immobilization for 30 min, with induction and recovery time and quality similar to other medetomidine-based combinations used in elk. Cardiopulmonary effects included bradycardia, hypertension, and hypoxemia that resolved with oxygen supplementation. The average injection volume in the low-dose alfaxalone combination was approximately 5 ml. These combinations provided deep sedation and the ability to perform minor procedures in captive elk, with acceptable cardiopulmonary parameters as long as supplemental oxygen was provided.


Assuntos
Azaperona/farmacologia , Cervos , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Medetomidina/farmacologia , Pregnanodionas/farmacologia , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Azaperona/administração & dosagem , Estudos Cross-Over , Quimioterapia Combinada , Feminino , Hipnóticos e Sedativos/administração & dosagem , Medetomidina/administração & dosagem , Pregnanodionas/administração & dosagem
12.
J Zoo Wildl Med ; 51(4): 848-855, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480565

RESUMO

Evaluation of sex ratios is a critical component of chelonian captive breeding programs and may become increasingly useful to assess the demographics of free-living populations. In many reptile species, the sex of immature animals cannot be determined based on external features. Endoscopic sex identification is an accurate and safe method to identify the sex of immature individuals of some chelonian species. A number of studies describe this technique in controlled, hospital settings and report significant interspecies variations in gonad morphology; however, there are few reports describing this technique in field conditions. In the current study, the gonadal morphology of 40 immature Western Santa Cruz tortoises (Chelonoidis porteri) on Santa Cruz Island in Galapagos, Ecuador, was assessed. A previously described endoscopic protocol was used to perform sex identification under field conditions. Tortoises were anesthetized using an intramuscular injection of ketamine (10 mg/kg) and medetomidine (0.1 mg/kg), which provided an adequate plane of anesthesia. The medetomidine was reversed with atipamezole (0.5 mg/kg). Field conditions presented challenges such as limited control over lighting, suboptimal patient positioning, and restricted power supply for endoscopy equipment. The immature testicle in Western Santa Cruz tortoises was oval, reddish pink, and tightly adhered to the coelomic membrane ventral to the kidney. The surface of the gonads resembled other species with the notable exception that the ovaries lacked a significant number of primordial follicles. These gonadal characteristics were consistent, with only one individual identified as undetermined sex of the 40 samples. This field-based endoscopic gonadal evaluation was a safe and sensitive technique for determining the sex of free-living immature Western Santa Cruz Galapagos tortoises.


Assuntos
Anestesia/veterinária , Ovário/anatomia & histologia , Maturidade Sexual , Testículo/anatomia & histologia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Medetomidina/administração & dosagem , Medetomidina/farmacologia , Ovário/crescimento & desenvolvimento , Testículo/crescimento & desenvolvimento , Tartarugas/fisiologia
13.
Water Res ; 191: 116791, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433334

RESUMO

Medetomidine has been authorized in ship hull paints as an antifouling biocide under the biocidal product regulation in Europe since 2016. Its release into marine systems causes concerns over persistence and toxicity. However, the environmental fate of medetomidine has not been fully investigated. In this study, the photodegradation of medetomidine under natural sunlight conditions was investigated using collected coastal and sea waters. In addition, the phototransformation of medetomidine with reactive species (i.e., singlet oxygen, excited triplet state organic matter, and hydroxyl radicals) under UVA light was examined. Photoproducts were isolated by high-performance liquid chromatography (HPLC), identified by a combination of nuclear magnetic resonance (NMR) spectroscopy and time-of-flight mass spectrometry (qTOF), and reaction mechanisms were proposed. The results show that medetomidine is a neutral base (pKa of protonated form = 7.2) that leads to two different protonation states in the aquatic environment. Photodegradation of neutral medetomidine was dominated by reaction with singlet oxygen, while protonated medetomidine was relatively photostable. The contribution of reactive species to the overall photodegradation of neutral medetomidine was calculated to provide an assessment of phototransformation of medetomidine. The half-live of medetomidine was < 1.5 days in natural waters (pHcoastal = 8.3; pHsea = 8.1) under sunlit near-surface conditions, suggesting that it is not persistent in the aquatic environment. Because medetomidine has a relatively short half-life in sunlit aquatic ecosystems, a number of products, such as 2-(2,3-dimethylphenyl)propanamide, can be formed by photochemical reactions of medetomidine, with unknown consequences for marine and coastal waters.


Assuntos
Medetomidina , Poluentes Químicos da Água , Ecossistema , Europa (Continente) , Cinética , Fotólise , Poluentes Químicos da Água/análise
14.
Neuroimage ; 224: 117415, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011419

RESUMO

The ability of different groups of cortical neurons to engage in causal interactions that are at once differentiated and integrated results in complex dynamic patterns. Complexity is low during periods of unconsciousness (deep sleep, anesthesia, unresponsive wakefulness syndrome) in which the brain tends to generate a stereotypical pattern consisting of alternating active and silent periods of neural activity-slow oscillations- and is high during wakefulness. But how is cortical complexity built up? Is it a continuum? An open question is whether cortical complexity can vary within the same brain state. Here we recorded with 32-channel multielectrode arrays from the cortical surface of the mouse and used both spontaneous dynamics (wave propagation entropy and functional complexity) and a perturbational approach (a variation of the perturbation complexity index) to measure complexity at different anesthesia levels. Variations in anesthesia level within the bistable regime of slow oscillations (0.1-1.5 Hz) resulted in a modulation of the slow oscillation frequency. Both perturbational and spontaneous complexity increased with decreasing anesthesia levels, in correlation with the decrease in coherence of the underlying network. Changes in complexity level are related to, but not dependent on, changes in excitability. We conclude that cortical complexity can vary within a single brain state dominated by slow oscillations, building up to the higher complexity associated with consciousness.


Assuntos
Anestésicos Gerais/farmacologia , Ondas Encefálicas/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Anestesia Geral , Animais , Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiologia , Estimulação Elétrica , Eletroencefalografia , Hipnóticos e Sedativos/farmacologia , Isoflurano/farmacologia , Ketamina/farmacologia , Medetomidina/farmacologia , Camundongos
15.
Vet Anaesth Analg ; 47(5): 667-671, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32792270

RESUMO

OBJECTIVE: To investigate the effects of sedative doses of intravenous (IV) medetomidine (MED) or dexmedetomidine (DEX) on selected respiratory variables in dogs. STUDY DESIGN: Randomized, blinded, crossover study. ANIMALS: A total of eight healthy adult research Beagles. METHODS: Dogs breathing room air had an electrical impedance tomography belt placed around the chest and were maintained in right lateral recumbency. Respiratory rate (fR) in movements minute-1 (mpm) and changes in thoracic impedance (ΔZ) in arbitrary units (AU) were recorded for 120 seconds before (T0) and exactly 10 minutes (T10) after the administration of IV DEX (10 µg kg-1) or MED (20 µg kg-1), with a minimum washout period of 10 days between treatments. Minute ΔZ (ΔZ˙) was calculated by multiplying median ΔZ with fR. Data are presented as median (interquartile range). Significance for an overall effect of drugs (DEX versus MED) or treatment (T0 versus T10) was quantified with a two-way analysis of variance for repeated measures, followed by, when appropriate, Wilcoxon's signed rank test for each factor. RESULTS: Overall, fR decreased from 26 (22-29) mpm at T0 to 13 (10-21) mpm at T10 (p = 0.003) and ΔZ increased from 1.133 (0.856-1.599) AU at T0 to 1.650 (1.273-2.813) AU at T10 (p = 0.007), but ΔZ˙ did not change [30.375 (23.411-32.445) AU minute-1 at T0 and 30.581 (22.487-35.091) AU minute-1 at T10]. There was no difference between DEX and MED. Most dogs developed a peculiar breathing pattern characterized by clusters of breaths followed by short periods of apnoea. CONCLUSIONS AND CLINICAL RELEVANCE: Both drugs caused a change in breathing pattern, reduction in fR and increase in ΔZ but did not affect ΔZ˙. It is likely that (dex)medetomidine resulted in reduction in fR and increase in tidal volume without impacting minute volume.


Assuntos
Dexmedetomidina/farmacologia , Cães , Hipnóticos e Sedativos/farmacologia , Medetomidina/farmacologia , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Animais , Estudos Cross-Over , Feminino , Masculino
16.
Schweiz Arch Tierheilkd ; 162(9): 539-550, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32855121

RESUMO

INTRODUCTION: This study observed the effects of three different surgical positions on arterial blood oxygenation measured noninvasively by pulse oximetry (SpO2) and on intraocular pressure (IOP) in anaesthetised cats undergoing spay. A total of 222 female feral cats were anaesthetised for a large-scale trap-neuter-return program with an intramuscular combination of medetomidine (0.03 - 0.05 mg/kg), ketamine (7 - 10 mg/kg) and butorphanol (0.4 mg/kg). Cats were randomly allocated to undergo spay in either Trendelenburg (70° downward head tilt), lateral or dorsal recumbency. SpO2 and pulse rate were measured at baseline, prior to surgical positioning, after one minute in surgical position and in one-minute intervals after surgical incision. Intraocular pressure was measured before positioning and at the end of surgery. At the end of surgery, all cats were placed into left lateral recumbency and all parameters were revaluated after five minutes. No significant differences between the three positions were found regarding SpO2, but an increase over time was observed. In total, 52 ± 10% (mean ± SD) of cats were hypoxaemic (SpO2 < 90%) at baseline. SpO2 improved over time, but 27 ± 3% (mean ± SD) of the cats remained hypoxaemic at the end of surgery. Trendelenburg position increased IOP during surgery (mean 31 ± 6 mmHg, individual max. 48 mmHg, versus 17 ± 4 mmHg in dorsal/lateral recumbency) but normalised after 5 mins in lateral recumbence. All cats recovered well from surgery and were released within 24 hours post-anaesthesia. Surgical position was shown to have no notable influence on SpO2 during anaesthesia in cats not receiving oxygen supplementation, whereas Trendelenburg position led to increased IOP. Oxygen supplementation is recommended with this anaesthetic protocol, as hypoxaemia is frequently observed.


Assuntos
Analgésicos/efeitos adversos , Posicionamento do Paciente/veterinária , Esterilização Reprodutiva/veterinária , Analgésicos/administração & dosagem , Animais , Butorfanol/administração & dosagem , Butorfanol/efeitos adversos , Gatos , Pressão Intraocular/efeitos dos fármacos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Esterilização Reprodutiva/efeitos adversos
17.
Aust Vet J ; 98(10): 511-516, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32643182

RESUMO

OBJECTIVE: To characterise intramuscular ketamine-medetomidine-tramadol anaesthesia in hatchling green sea turtles (Chelonia mydas). STUDY DESIGN: Prospective clinical trial. ANIMALS: Ten hatchling green sea turtles. MATERIALS AND METHODS: Prior to anaesthesia, cardiopulmonary parameters, cloacal temperature, and venous blood gas and biochemistry were obtained from hatchling green sea turtles while they were being gently restrained. Animals were then anaesthetised with ketamine (5 mg kg-1 ), medetomidine (0.05 mg kg-1 ) and tramadol (5 mg kg-1 ) via intramuscular injection. Turtles were checked for the depth of anaesthesia at five-min intervals by recording reflexes (righting, palpebral, pinch, cloacal) and measuring heart rate, respiratory rate and cloacal temperature. After 20 min, a second venous blood sample was obtained for further blood gas and biochemical analysis and the medetomidine was antagonised using atipamezole (5:1 medetomidine, 0.25 mg kg-1 ). RESULTS: All turtles were successfully anaesthetised with a mean time to induction of 3.4 min (±1). In all animals, a loss of reflexes (except for palpebral reflex) and voluntary movement was observed for the entire 20 min. Anaesthesia resulted in marked apnoea for the duration of the procedure. Venous blood gas and biochemistry analysis indicated that a 20 min period of apnoea had no measurable effects on venous blood gas results. All turtles recovered uneventfully after atipamazole antagonisation, with a mean time to first breath 4.5 min (±3.7), and mean recovery time 15.5 min (±15.4). CONCLUSIONS AND CLINICAL RELEVANCE: Intramuscular ketamine-medetomidine-tramadol, antagonised with atipamazole appears to be an effective anaesthetic protocol in hatchling green sea turtles for short procedures with no deleterious effects on venous blood gases or biochemistry.


Assuntos
Anestesia/veterinária , Ketamina , Tramadol , Tartarugas , Anestésicos Combinados , Animais , Injeções Intramusculares/veterinária , Medetomidina , Estudos Prospectivos
18.
Vet Anaesth Analg ; 47(5): 604-613, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682664

RESUMO

OBJECTIVE: To investigate the impact of intramuscular (IM) co-administration of the peripheral α2-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal. STUDY DESIGN: Randomized, masked crossover study. ANIMALS: A total of eight purpose-bred Beagle dogs aged 3 years. METHODS: Each dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 µg kg-1) and butorphanol (100 µg kg-1) premedication with vatinoxan (500 µg kg-1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg-1). Atipamezole (100 µg kg-1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed. RESULTS: At most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57-59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB. CONCLUSIONS AND CLINICAL RELEVANCE: Haemodynamic performance was improved by vatinoxan co-administration with medetomidine-butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.


Assuntos
Anestesia/veterinária , Butorfanol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Medetomidina/farmacologia , Quinolizinas/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Butorfanol/administração & dosagem , Estudos Cross-Over , Cães , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Masculino , Medetomidina/administração & dosagem , Quinolizinas/administração & dosagem , Resistência Vascular
19.
Vet Anaesth Analg ; 47(4): 518-527, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32507716

RESUMO

OBJECTIVE: To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine-tiletamine-zolazepam in red deer (Cervus elaphus). STUDY DESIGN AND ANIMALS: A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study. METHODS: Deer were administered a combination of 0.1 mg kg-1 medetomidine hydrochloride and 2.5 mg kg-1 tiletamine-zolazepam intramuscularly, followed by 0.1 mg kg-1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (Pe'CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05). RESULTS: Maximal (81 ± 10 beats minute-1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute-1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute-1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe'CO2, fR and SpO2 showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan. CONCLUSIONS AND CLINICAL RELEVANCE: Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine-tiletamine-zolazepam.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Cervos , Medetomidina , Quinolizinas/farmacologia , Tiletamina , Zolazepam , Anestésicos Combinados/efeitos adversos , Anestésicos Intravenosos , Animais , Bradicardia/induzido quimicamente , Bradicardia/prevenção & controle , Bradicardia/veterinária , Estudos Cross-Over , Interações Medicamentosas , Feminino , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Hipertensão/veterinária , Masculino , Medetomidina/efeitos adversos , Tiletamina/efeitos adversos , Zolazepam/efeitos adversos
20.
Neuroimage ; 219: 116945, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497787

RESUMO

Under anesthesia, systemic variables and CBF are modified. How does this alter the connectivity measures obtained with rs-fMRI? To tackle this question, we explored the effect of four different anesthetics on Long Evans and Wistar rats with multimodal recordings of rs-fMRI, systemic variables and CBF. After multimodal signal processing, we show that the blood-oxygen-level-dependent (BOLD) variations and functional connectivity (FC) evaluated at low frequencies (0.031-0.25 â€‹Hz) do not depend on systemic variables and are preserved across a large interval of baseline CBF values. Based on these findings, we found that most brain areas remain functionally active under any anesthetics, i.e. connected to at least one other brain area, as shown by the connectivity graphs. In addition, we quantified the influence of nodes by a measure of functional connectivity strength to show the specific areas targeted by anesthetics and compare correlation values of edges at different levels. These measures enable us to highlight the specific network alterations induced by anesthetics. Altogether, this suggests that changes in connectivity could be evaluated under anesthesia, routinely used in the control of neurological injury.


Assuntos
Encéfalo/efeitos dos fármacos , Etomidato/farmacologia , Isoflurano/farmacologia , Medetomidina/farmacologia , Rede Nervosa/efeitos dos fármacos , Uretana/farmacologia , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Animais , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/efeitos dos fármacos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Ratos , Ratos Long-Evans
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