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1.
J Anal Toxicol ; 48(1): 54-61, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37978839

RESUMO

The barbiturate drug pentobarbital is commonly used by veterinarians for the euthanasia of domestic animals. During the veterinary forensic autopsy, it is sometimes necessary to determine whether the animal was chemically euthanized with pentobarbital. The use of a human immunochromatographic test for barbiturate screening utilizing dog or cat urine has been previously validated; however, the use of alternative matrices for this purpose is yet to be explored when urine is not available. Postmortem heart, liver, spleen, skeletal muscle, blood and/or urine samples from 20 dogs and 26 cats with a reported chemical euthanasia status were processed using two different methods, bead homogenization and sonication, and screened for barbiturates using a human immunochromatographic test. There was 100% agreement of the immunochromatographic test results using the sonication method with the reported euthanasia status of both dogs and cats. Using the bead homogenization method, agreement with the reported euthanasia status was 93.3% and 96.7% for dogs and cats, respectively, due to invalid test results from four dog and two cat samples. A subset of liver samples (10 canine and 10 feline) was analyzed via gas chromatography-mass spectrometry, and there was 100% agreement between the immunochromatographic test results and gas chromatography-mass spectrometry results for both cats and dogs. Overall, our results support the use of a variety of alternative matrices for barbiturate screening in cats and dogs.


Assuntos
Doenças do Gato , Doenças do Cão , Humanos , Gatos , Cães , Animais , Pentobarbital/análise , Barbitúricos , Imunoensaio , Animais Domésticos
2.
Stud Health Technol Inform ; 308: 42-47, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38007723

RESUMO

Insomnia is one of the most common sleep-related diseases. In traditional Chinese medicine, Flos daturae has been used as a traditional herbal totreatment of sizens of diseases. The research objective was to investigate the sedative and hypnotic effects of Flos Daturae. Kunming mice were divided into control group, Estazolam (positive drug, 0.0005 g/kg) group and Flos Daturae groups (0.01, 0.02, 0.04g/kg) with random, ig once a day for 7 days. The central sedative effect of flos Daturae on the spontaneous activity of mice was observed using the locomotive activity test, and the hypnotic effect of Flos Daturae was observed in mice using the direct sleep test and the sleep latency with synergistic supra-and sub-threshold doses of pentobarbital sodium. Flos Daturae (0.04g/kg) significantly inhibited mice locomotive activity (P<0.05) and had no direct sleeping effect (P>0.05), increased the number rate of sleep (P<0.05), and significantly shortening sleep latency (P<0.05), enhanced pentobarbital sodium-induced sleep. Flos Daturae possesses have sedative-hypnotic properties.


Assuntos
Hipnóticos e Sedativos , Distúrbios do Início e da Manutenção do Sono , Camundongos , Animais , Hipnóticos e Sedativos/farmacologia , Pentobarbital/farmacologia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono
3.
MMW Fortschr Med ; 165(20): 37, 2023 11.
Artigo em Alemão | MEDLINE | ID: mdl-37973746
4.
Am J Surg ; 226(6): 864-867, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37532593

RESUMO

INTRODUCTION: Traumatic brain injury (TBI) results in the death of over 50,000 and the permanent disability of 80,000 individuals annually in the United States. Much of the permanent disability is the result of secondary brain injury from intracranial hypertension (ICH). Pentobarbital coma is often instituted following the failure of osmotic interventions and sedation to control intracranial pressure (ICP). The goal of this study was to evaluate the efficacy of pentobarbital coma with respect to ICP management and long-term functional outcome. METHODS: Traumatic brain injury patients who underwent pentobarbital coma at a level 1 trauma center between 2014 and 2021 were identified. Patient demographics, injury characteristics, Glasgow Coma Scale (GCS) scores, intracranial pressures (ICPs), and outcomes were obtained from the trauma registry as well as inpatient and outpatient medical records. The proportion of ICPs below 20 for each hospitalized patient-day was calculated. The primary outcome measured was GCS score at the last follow-up visit. RESULTS: 25 patients were identified, and the majority were male (n â€‹= â€‹23, 92%) with an average age of 30.0 years â€‹± â€‹12.9 and median injury severity score of 30 (21.5-33.5). ICPs were monitored for all patients with a median of 464 (326-1034) measurements. The average hospital stay was 16.9 days â€‹± â€‹11.5 and intensive care stay was 16.9 â€‹± â€‹10.8 days. 9 (36.0%) patients survived to hospital discharge. Mean follow-up time in months was 36.9 â€‹± â€‹28.0 (min-max 3-80). 7 of the 9 surviving patients presented as GCS 15 on follow-up and the remaining were both GCS 9. Patients presenting at last follow-up with GCS 15 had a significantly higher proportion of controlled ICPs throughout their hospitalization compared to patients who expired or with follow-up GCS <15 (GCS 15: 88% â€‹± â€‹10% vs. GCS <15 or dead: 68% â€‹± â€‹22%, P â€‹= â€‹0.006). A comparison of the daily proportion of controlled ICPs by group revealed negligible differences prior to pentobarbital initiation. Groups diverged nearly immediately upon pentobarbital coma initiation with a higher proportion of controlled ICPs for patients with follow-up GCS of 15. CONCLUSION: Patients that do not have an immediate response to pentobarbital coma therapy for ICH universally had poor outcomes. Alternative therapy or earlier palliation should be considered for such patients. In contrast, patients whose ICPs responded quickly to pentobarbital had excellent long-term outcomes.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Hipertensão Intracraniana , Humanos , Masculino , Feminino , Adulto , Coma/complicações , Pentobarbital/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Escala de Coma de Glasgow , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/complicações , Pressão Intracraniana
5.
6.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37328163

RESUMO

A sodium pentobarbital-induced sleep time study was conducted on 15 adult intact male Boer × Spanish goats selected for high (J+, n = 7) or low (J-, n = 8) juniper consumption (estimated breeding values of 13.1 ± 1.0 and -14.3 ± 0.8, respectively; mean ± standard deviation). Pentobarbital sleep time is an in vivo assay of Phase I hepatic metabolism that can be induced by exposure to barbiturates and monoterpenes. Monoterpenes and pentobarbital are initially oxidized by this pathway; thus, we hypothesized that J+ goats would have shorter sleep times than J- goats. Time to the righting reflex after pentobarbital-induced sleep was measured in all goats following a minimum period of 21 d on three different diets: 1) grazing juniper-infested rangeland (JIR), 2) forage diet with no monoterpenes (M0), and 3) forage diet with 8 g/kg added monoterpenes from camphor, sabinene, and α-pinene in a w/w ratio of 5:4:1 (M+). Fecal samples from the JIR diet were analyzed with near-infrared spectroscopy for the percentage of juniper in the diet. Fecal samples from the JIR and M+ diets were analyzed for camphor and sabinene concentrations. The percentage of juniper in the diet of J+ goats grazing rangelands was greater (P = 0.001) than J- goats (31.1% and 18.6%, respectively). Sleep time did not differ between selection lines (P = 0.36). However, the sleep time of the goats fed M+ diet was 26 min shorter (P < 0.001) than JIR or M0 diets, which were equal. The concentration of camphor and sabinene in the feces was higher (P < 0.001) for goats on the M+ diet than on the JIR diet. There were no differences between selection lines in the serum enzymes indicative of liver disease (aspartate aminotransferase, bilirubin, gamma-glutamyl transferase, and glutamate dehydrogenase; P > 0.12), and all treatment means were within the reference interval. Selecting goats for juniper consumption did not affect the Phase I detoxification system, and several alternative hypotheses for differences in juniper consumption between J+ and J- goats are discussed.


Juniper is an encroaching woody plant with high levels of essential oils and condensed tannins that can limit its consumption by herbivores. Goats were divergently selected for 15 yr to increase or decrease their juniper consumption. This study was conducted to determine if a physiological pathway for metabolism of essential oils differed between high and low juniper-consuming goat lines. The metabolic pathway for the elimination of essential oils is similar to that of the barbiturate pentobarbital. A pentobarbital-induced sleep time was used to detect differences in detoxification rates between the divergent goat lines selectively bred for either a high or low percentage of juniper in their diet. We hypothesized that high juniper-consuming goats would have shorter sleep times, indicating their detoxification pathway was more active. However, there was no difference between these lines. Additionally, there were no differences between the selection lines in blood metabolites that indicate liver tissue damage or liver weights. Therefore, higher dietary juniper preference may be associated with other detoxification mechanisms, may not be limited by essential oils, or may be a socially facilitated learned behavior.


Assuntos
Juniperus , Animais , Masculino , Juniperus/química , Cabras , Cânfora , Desentoxicação Metabólica Fase I , Pentobarbital , Melhoramento Vegetal , Dieta/veterinária , Monoterpenos , Fígado
7.
J Food Drug Anal ; 31(2): 278-288, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37335157

RESUMO

Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities, such as improving cognitive function, immunity and anxiety. In this study, the effect of enzyme-treated Ashwagandha root extract (EA) and on sleep was evaluated using rodent models. Starch contained in the Ashwagandha root extract was removed by amylase treatment to prepare EA. To evaluate the sleep-promoting activity of EA, a pentobarbital-induced sleep test and electroencephalogram analysis were performed. In addition, the sleep-promoting mechanism of EA was elucidated by analyzing the expression of sleep-related receptors. In the pentobarbital-induced sleep test, EA dose-dependently increased sleep duration. Additionally, electroencephalogram analysis revealed that EA significantly increased δ-wave and non-rapid eye movement sleep times, which are involved in deep sleep, thereby improving sleep quality and quantity. EA also effectively relieved caffeine-induced insomnia symptoms. Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABAA, GABAB1, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites. Collectively, EA exhibited sleep-promoting activity through the GABAergic system and may be used as a functional material to improve sleep deprivation.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Withania , Receptores de GABA , Withania/química , Pentobarbital/farmacologia , Amilases/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Sono , Ácido gama-Aminobutírico
9.
Am J Vet Res ; 84(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37142234

RESUMO

OBJECTIVE: To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta). ANIMALS: 16 pond slider turtles (T. scripta). PROCEDURES: Pentobarbital 100 mg/kg was delivered through esophageal gavage (n = 8) or cloacal administration (8). The presence of voluntary movement, heart rate (HR), respiratory rate (RR), palpebral reflex, corneal reflex, and response to noxious stimuli were recorded until death, confirmed via the absence of reflexes, movement, heartbeat, and absence of cardiac electrical activity. RESULTS: No signs of irritation were observed in any turtles. Leakage after administration occurred in 75% (6/8) of the cloacal group, including 2 turtles with marked leakage or expulsion. Two of eight turtles in the cloacal group regained movement and required euthanasia by a standard method and 1 turtle in the oral group was excluded from further analysis due to a miscalculated dose. The remaining 13 turtles (7/8 oral, 6/8 cloacal) had cessation of a heartbeat at a median of 18 hours (range = 6 to 26 hours) with respiratory arrest occurring within 15 minutes. The median time to loss of corneal reflex was 45 minutes (range = 15 minutes to 4 hours). Time-to-loss of parameters was similar between oral and cloacal routes, respectively. CLINICAL RELEVANCE: Transmucosally administered pentobarbital via the oral and cloacal routes both result in euthanasia within approximately 24 hours. Given that 25% of the turtles in the cloacal group required a secondary method of euthanasia, the oral route is a preferred route to induce euthanasia in pond turtles.


Assuntos
Tartarugas , Animais , Pentobarbital , Eutanásia Animal , Piscadela , Frequência Cardíaca
10.
Vet Res Commun ; 47(4): 2265-2269, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37145336

RESUMO

A bearded vulture (Gypaetus barbatus) found dead in northern Spain presented external lesions consistent with electrocution as the cause of death. During forensic examination, macroscopic lesions suggested potential comorbidity, so samples were collected for molecular and toxicological analyses. Gastric content and liver were analysed for toxic substances, and pentobarbital (a common pharmaceutical used for euthanasia in domestic animals) was detected at a concentration of 37.3 and 0.05 µg/g, respectively. Other toxicological, viral and endoparasite analyses (avian malaria, avian influenza and flaviviruses) were negative. Thus, although the cause of death was electrocution, pentobarbital intoxication likely impaired the equilibrium and reflexes of the individual, possibly causing the bird to contact energized wires that it would not have otherwise. These results underline the importance of comprehensive analysis of forensic cases of wildlife deaths and reveal barbiturate poisoning as an additional threat for the conservation of the bearded vulture in Europe.


Assuntos
Falconiformes , Venenos , Animais , Pentobarbital , Aves , Espanha
11.
Clin Pharmacokinet ; 62(7): 1011-1022, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37247187

RESUMO

BACKGROUND: Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI). OBJECTIVES: To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations. METHODS: Develop a PopPK model with non-linear mixed-effects modelling (NONMEM®) with retrospective data (n = 36; median age 1.3 years; median weight 10 kg; 178 blood samples) treated with continuous intravenous pentobarbital. An independent dataset was used for external validation (n = 9). Dosing simulations with the validated model evaluated dosing regimens. RESULTS: A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (Vd; 1) captured data well. Typical CL and Vd values were 3.59 L/70 kg/h and 142 L/70 kg, respectively. Elevated creatinine and C-reactive protein (CRP) levels significantly correlated to decreased CL, explaining 84% of inter-patient variability, and were incorporated in the final model. External validation using stratified visual predictive checks showed good results. Simulations demonstrated patients with elevated serum creatinine and CRP failed to achieve steady state yet progressed to toxic levels with current dosing regimens. CONCLUSIONS: The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.


Assuntos
Lesões Encefálicas Traumáticas , Estado Epiléptico , Humanos , Criança , Lactente , Antibacterianos/farmacocinética , Pentobarbital , Creatinina , Estado Terminal , Estudos Retrospectivos , Estudos Prospectivos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico
12.
J Nat Med ; 77(3): 561-571, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37115471

RESUMO

Nerve inflammation is linked to the development of various neurological disorders. This study aimed to examine whether Glycyrrhizae Radix effectively influences the duration of the pentobarbital-induced loss of righting reflex, which may increase in a mouse model of lipopolysaccharide (LPS)-induced nerve inflammation and diazepam-induced γ-aminobutyric acid receptor hypersensitivity. Furthermore, we examined the anti-inflammatory effects of Glycyrrhizae Radix extract on LPS-stimulated BV2 microglial cells, in vitro. Treatment with Glycyrrhizae Radix significantly decreased the duration of pentobarbital-induced loss of righting reflex in the mouse model. Furthermore, treatment with Glycyrrhizae Radix significantly attenuated the LPS-induced increases in interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha at the mRNA level, and it significantly reduced the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus 24 h after LPS treatment. Treatment with Glycyrrhizae Radix also suppressed the release of nitric oxide, interleukin-1ß, interleukin-6, and tumor necrosis factor protein in culture supernatants of LPS-stimulated BV2 cells. In addition, glycyrrhizic acid and liquiritin, active ingredients of Glycyrrhizae Radix extract, reduced the duration of pentobarbital-induced loss of righting reflex. These findings suggest that Glycyrrhizae Radix, as well as its active ingredients, glycyrrhizic acid and liquiritin, may be effective therapeutic agents for the treatment of nerve inflammation-induced neurological disorders.


Assuntos
Medicamentos de Ervas Chinesas , Glycyrrhiza , Camundongos , Animais , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Ácido Glicirrízico/farmacologia , Pentobarbital/farmacologia , Pentobarbital/uso terapêutico , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Diazepam/uso terapêutico , Reflexo de Endireitamento , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Hipocampo/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
13.
Theriogenology ; 205: 1-8, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37084499

RESUMO

Postmortem and pre-euthanasia oocyte retrieval provides the last opportunity to preserve the genetic material in mares. Pentobarbital (PB) is the most common euthanasia agent; however, its effect on the developmental competence of oocytes has not been determined. Here, we evaluated the concentration of PB in equine follicular fluid (FF) and investigated its effect on the developmental competence of oocytes using a bovine IVF model to overcome the low availability of equine oocytes. The concentration of PB was measured by gas-chromatography/mass-spectrometry in FF collected from mare ovaries immediately after euthanasia (n = 10), 24 h post-euthanasia (n = 10), and from the ovaries collected by ovariectomy (negative control; n = 10). The serum concentration of PB was also evaluated as a positive control. PB was detected in all FF samples with an average concentration of 56.5 µg/ml. Next, bovine cumulus-oocyte complexes (COC) were held in holding media with PB for 6 h at 60 µg/ml (H60, n = 196), 164 µg/ml (H164, n = 215) or without PB (control; n = 212). After holding, the oocytes were matured and fertilized in vitro, followed by in vitro culture to the blastocyst stage. The cumulus expansion grade, cleavage rate, blastocyst rate, embryo kinetic rate and the blastocyst cell numbers were compared among the experimental groups of bovine COC. Higher rates of Grade 1 cumulus expansion were found in controls (54%, 32-76%; median, min-max) in comparison to H60 and H164 (24%,11-33% and 13%, 8-44%; P < 0.001). The cleavage rate was higher in the controls than in H164 (64% vs. 44%; P < 0.01). Blastocyst rates (blastocyst/cleaved oocytes) and total cell number were not different among the groups (control 29%, H60 25%, and H164 24%). In a preliminary study, equine oocytes (n = 28) were exposed to PB in vitro for 6 h followed by intracytoplasmic sperm injection (ICSI) and in vitro embryo production. Exposed oocytes showed a numerically lower maturation rate (43% Vs 52%; P > 0.05) in comparison to the laboratory-established rate during the same timepoints. Overall, we showed that PB reaches the FF immediately after euthanasia, exposing oocytes to this drug. This exposure affected cumulus expansion and cleavage rates in a bovine model, suggesting initial damage caused by PB that may not completely impede the formation of embryos, although lower overall embryo numbers might be obtained.


Assuntos
Pentobarbital , Sêmen , Animais , Cavalos , Feminino , Masculino , Bovinos , Pentobarbital/farmacologia , Eutanásia Animal , Oócitos , Embrião de Mamíferos , Blastocisto , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Fertilização In Vitro/veterinária
14.
Sci Rep ; 13(1): 4537, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941315

RESUMO

Sudden cardiac arrest (SCA) is a leading cause of mortality worldwide. The SCA-to-resuscitation interval is a key determinant of patient outcomes, highlighting the clinical need for reliable and timely detection of SCA. Near-infrared spectroscopy (NIRS), a non-invasive optical technique, may have utility for this application. We investigated transcutaneous NIRS as a method to detect pentobarbital-induced changes during cardiac arrest in eight Yucatan miniature pigs. NIRS measurements during cardiac arrest were compared to invasively acquired carotid blood pressure and partial oxygen pressure (PO2) of spinal cord tissues. We observed statistically significant decreases in mean arterial pressure (MAP) 64.68 mmHg ± 13.08, p < 0.0001), spinal cord PO2 (38.16 mmHg ± 20.04, p = 0.0028), and NIRS-derived tissue oxygen saturation (TSI%) (14.50% ± 3.80, p < 0.0001) from baseline to 5 min after pentobarbital administration. Euthanasia-to-first change in hemodynamics for MAP and TSI (%) were similar [MAP (10.43 ± 4.73 s) vs TSI (%) (12.04 ± 1.85 s), p = 0.3714]. No significant difference was detected between NIRS and blood pressure-derived pulse rates during baseline periods (p > 0.99) and following pentobarbital administration (p = 0.97). Transcutaneous NIRS demonstrated the potential to identify rapid hemodynamic changes due to cardiac arrest in periods similar to invasive indices. We conclude that transcutaneous NIRS monitoring may present a novel, non-invasive approach for SCA detection, which warrants further investigation.


Assuntos
Parada Cardíaca , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Suínos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Pentobarbital , Parada Cardíaca/diagnóstico , Medula Espinal , Modelos Animais , Morte Súbita Cardíaca , Oxigênio
15.
Am J Vet Res ; 84(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36921025

RESUMO

OBJECTIVES: This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous injection of pentobarbital in sedated horses. ANIMALS: Client-owned horses and horses requiring euthanasia due to involvement in concurrent research projects were used. Horses were randomly assigned to 1 of 2 groups: intrathecal mepivacaine after anesthesia or intravenous pentobarbital after sedation. All horses had normal vital parameters and no signs of infectious disease at the time of euthanasia. PROCEDURES: The intrathecal mepivacaine group was anesthetized before the intrathecal injection of mepivacaine. The pentobarbital group was sedated, concurrently anesthetized and euthanized using intravenous pentobarbital, then received an intrathecal saline (0.9% NaCl) solution injection to a blind observer. Both groups were sedated with detomidine and the time from sedation to the cessation of vital parameters (respirations, pulse, corneal reflex, and ECG) was recorded. Euthanasias were recorded for review by a blinded anesthesiologist, using an independent scale to assess the quality of sedation, anesthesia induction, and lateral recumbency. RESULTS: Time from detomidine administration to cessation of each vital parameter was significantly longer in the intrathecal mepivacaine group. There was no statistically significant difference in qualitative scores between groups for sedation or induction, but lateral recumbency was subjectively superior in the anesthetized intrathecal mepivacaine group. CLINICAL RELEVANCE: Intrathecal mepivacaine provided a safe, effective, alternative method of euthanasia to intravenous pentobarbital and addresses concerns about barbiturate availability. This study also informs practitioners of what to expect (ie, longer cessation of vital parameters) when using the intrathecal mepivacaine method.


Assuntos
Mepivacaína , Pentobarbital , Cavalos , Animais , Pentobarbital/farmacologia , Mepivacaína/farmacologia , Eutanásia Animal/métodos , Anestesia Geral/veterinária , Administração Intravenosa/veterinária
16.
Neurosci Lett ; 802: 137175, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36907265

RESUMO

Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.


Assuntos
Pentobarbital , Receptores de N-Metil-D-Aspartato , Camundongos , Animais , Pentobarbital/farmacologia , Maleato de Dizocilpina/farmacologia , Sarcosina/farmacologia , Mecamilamina , Ácido gama-Aminobutírico , Inconsciência
17.
J Am Assoc Lab Anim Sci ; 62(2): 185-188, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36889741

RESUMO

Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose should be used. The minimal dose of barbiturate for euthanasia in pigs under isoflurane anesthesia has not yet been determined. In this study, we compared the effect of low and high doses of 2 barbiturates (pentobarbital, 30 or 60 mg/kg; thiopental, 20 and 40 mg/kg) on hemodynamic parameters and time to cardiac arrest in female pigs maintained on isoflurane. Acute decreases in blood pressure and end-tidal CO2 occurred in all pigs shortly after administration of the barbiturate. However, these changes were not different between either of the high- and low dose groups. Cardiac arrest occurred significantly faster for high dose as compared with low dose thiopental groups, but this parameter was different between the 2 pentobarbital groups. The bispectral index fell immediately after dosing, in all pigs, but no significant differences were observed in the time needed to achieve 0 for the high or low-doses of either drug. In pigs maintained on isoflurane, a low dose of barbiturates is adequate for euthanasia and may result in less tissue damage.


Assuntos
Anestesia , Isoflurano , Feminino , Animais , Suínos , Pentobarbital , Tiopental , Barbitúricos , Anestesia/veterinária
18.
Nutrients ; 15(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36986039

RESUMO

Dried Chrysanthemum morifolium (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry extract (ext) and its active substance linarin were analyzed by pentobarbital-induced sleep experiment in mice and electroencephalography (EEG), electromyogram (EMG) analysis in rats. In a dose-dependent manner, Chry ext and linarin promoted longer sleep duration in the pentobarbital-induced sleep test compared to pentobarbital-only groups at both hypnotic and subhypnotic doses. Chry ext administration also significantly improved sleep quality, as seen in the relative power of low-frequency (delta) waves when compared with the control group. Linarin increased Cl- uptake in the SH-SY5Y human cell line and chloride influx was reduced by bicuculline. After administration of Chry ext, the hippocampus, frontal cortex, and hypothalamus from rodents were collected and blotted for glutamic acid decarboxylase (GAD)65/67 and gamma-aminobutyric acid (GABA)A receptors subunit expression levels. The expression of α1-subunits, ß2-subunits, and GAD65/67 of the GABAA receptor was modulated in the rodent brain. In conclusion, Chry ext augments pentobarbital-induced sleep duration and enhances sleep quality in EEG waves. These effects might be due to the activation of the Cl- channel.


Assuntos
Neuroblastoma , Pentobarbital , Ratos , Camundongos , Humanos , Animais , Pentobarbital/farmacologia , Receptores de GABA-A , Qualidade do Sono , Roedores , Cloretos/metabolismo , Sono
19.
J Am Vet Med Assoc ; 261(5): 733-738, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36800298

RESUMO

Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA Guidelines for the Euthanasia of Animals: 2020 Edition lists barbiturate acid derivatives (pentobarbital) and pentobarbital combination products as an acceptable method of euthanasia for all species when circumstances permit their use. When using pentobarbital products, a veterinarian must consider appropriate handling and disposal of animal remains to avoid the potential for environmental contamination, relay toxicosis in wildlife or domestic animals, and contamination of the animal food supply. Failure to appropriately consider these facets of pentobarbital euthanasia can result in legal and ethical consequences. Despite these concerns, to the authors' knowledge no comprehensive literature review has been published concerning pentobarbital euthanasia or handling and disposal of animal remains following pentobarbital euthanasia. The literature review that follows aims to give a descriptive narrative of the most recent information available on the knowledge, use, challenges, and issues surrounding pentobarbital euthanasia and disposal of animal remains within the US.


Assuntos
Pentobarbital , Médicos Veterinários , Animais , Estados Unidos , Humanos , Pentobarbital/farmacologia , Restos Mortais , Eutanásia Animal , Animais Domésticos
20.
J Neurotrauma ; 40(23-24): 2552-2565, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36785968

RESUMO

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain.


Assuntos
Anestésicos , Contusões , Isoflurano , Traumatismos da Medula Espinal , Humanos , Ratos , Animais , Pentobarbital , Isoflurano/farmacologia , Dor/tratamento farmacológico , Dor/etiologia , Traumatismos da Medula Espinal/complicações , Anestesia Geral/efeitos adversos , Hemorragia , Contusões/complicações
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