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1.
J Zoo Wildl Med ; 50(4): 868-873, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926517

RESUMO

Blue poison dart frogs (Dendrobates tinctorius azureus) are commonly maintained in zoological institutions and are becoming popular in the pet trade industry. Sedation or light anesthesia is required for safe and effective handling of this species. In this study, the sedative effects of subcutaneously administered alfaxalone-midazolam-dexmedetomidine (AMD) (20, 40, 5 mg/kg, respectively) and ketamine-midazolam-dexmedetomidine (KMD) (100, 40, 5 mg/kg, respectively) were compared in a prospective, randomized, blinded, crossover study in juvenile blue poison dart frogs (n = 10). Both protocols were partially reversed 45 min after administration of either protocol with subcutaneously administered flumazenil (0.05 mg/kg) and atipamezole (50 mg/kg). Heart rate, pulmonic respiratory rate, various reflexes, and behavioral parameters were monitored after drug administration. Both protocols resulted in rapid loss of righting reflex [median (range): AMD, 5 min (5-5 min); KMD, 5 min (5-10 min)]. Time to complete recovery was similar with both protocols (mean ± SD: AMD, 97.5 ± 11.4 min; KMD, 96.5 ± 25.4 min). The AMD protocol resulted in pulmonic respiratory depression, whereas no significant difference in heart rate was found between the two protocols. All frogs were observed eating within 24 hr of chemical restraint. Gastric prolapses occurred in four frogs (AMD 3, KMD 1) that were easily reduced with a cotton-tip application. No other adverse reactions were observed. The results of this study provide two different subcutaneous chemical restraint protocols in juvenile blue poison dart frogs.


Assuntos
Dexmedetomidina/farmacologia , Midazolam/farmacologia , Pregnanodionas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Envelhecimento , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Antídotos/administração & dosagem , Antídotos/farmacologia , Anuros , Sedação Consciente , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Quimioterapia Combinada , Flumazenil/administração & dosagem , Flumazenil/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Midazolam/administração & dosagem , Pregnanodionas/administração & dosagem
2.
Acta Cir Bras ; 34(11): e201901105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859818

RESUMO

PURPOSE: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). METHODS: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. RESULTS: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). CONCLUSION: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Neuropatias Diabéticas/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Receptores Purinérgicos P2X4/análise , Coluna Vertebral/efeitos dos fármacos , Animais , Western Blotting , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/patologia , Modelos Animais de Doenças , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Transmissão , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Limiar da Dor , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores Purinérgicos P2X4/efeitos dos fármacos , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Coluna Vertebral/patologia , Estreptozocina , Nervo Sural/efeitos dos fármacos , Nervo Sural/patologia , Fatores de Tempo
4.
J Med Life ; 12(3): 260-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666828

RESUMO

Lower back pain is one of the leading causes of disability in the world. The aim of this study was to evaluate the effect of supplementation of dexmedetomidine and neostigmine with lidocaine 1.5% and triamcinolone for epidural block in increasing the duration of analgesia among patients suffering from chronic low back pain. In this double-blind, randomized clinical trial, 33 patients with chronic low back pain were included in three groups of 11 patients for epidural blockage. Triamcinolone (40 mg/ml) was added to lidocaine 1.5% solution (2 cc/segment) for all three groups. In group N, neostigmine was used at a dose of 1 mg (mg), followed by group D (dexmedetomidine 35 µg [0.5 µg/kg]), and grou [ND (neostigmine 0.5 mg, and 35 µg dexmedetomidine, all of which were added to the triamcinolone and lidocaine solution in each group. Medications were injected into the epidural space using an interlaminar approach. Subsequently, scores of pain and duration of analgesia were recorded in questionnaires and analysed using SPSS version 23. One month after the injections, pain scores recorded in the N group were 7.6±1.4, followed by 5.88±1.2 in group D and 5.42 ±1.1 in group ND. Therefore, the pain scores were significantly higher in the neostigmine group than the other two groups (p = 0.02), but no significant difference was found between the two groups that received dexmedetomidine and a combination of dexmedetomidine + neostigmine. Three months after the injections, there was a significant difference in pain scores between the two groups (P = 0.01). Both neostigmine and dexmedetomidine were capable of reducing the pain of patients with chronic low back pain after epidural block. However, neostigmine's impact is lower compared to dexmedetomidine. The combination of the two drugs also reduced the pain scores of the patients after the intervention.


Assuntos
Analgesia Epidural , Dor Crônica/tratamento farmacológico , Dexmedetomidina/uso terapêutico , Lidocaína/uso terapêutico , Dor Lombar/tratamento farmacológico , Neostigmina/uso terapêutico , Triancinolona/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Dor Crônica/fisiopatologia , Dexmedetomidina/farmacologia , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lidocaína/farmacologia , Dor Lombar/fisiopatologia , Masculino , Neostigmina/farmacologia , Oxigênio/metabolismo , Manejo da Dor , Triancinolona/farmacologia
5.
Br J Anaesth ; 123(6): 777-794, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668347

RESUMO

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. METHODS: We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. RESULTS: Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. CONCLUSIONS: DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Inflamação/tratamento farmacológico , Complicações Intraoperatórias/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Estresse Fisiológico/efeitos dos fármacos , Humanos , Imunidade , Período Pré-Operatório
6.
Nat Neurosci ; 22(11): 1782-1792, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31636451

RESUMO

Microglia are the brain's resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamics in vivo have been primarily studied in anesthetized animals. Here we report that microglial surveillance and injury response are reduced in awake mice as compared to anesthetized mice, suggesting that arousal state modulates microglial function. Pharmacologic stimulation of ß2-adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of ß2-adrenergic receptors in microglia. These results indicate that microglial roles in surveillance and synaptic plasticity in the mouse brain are modulated by noradrenergic tone fluctuations between arousal states and emphasize the need to understand the effect of disruptions of adrenergic signaling in neurodevelopment and neuropathology.


Assuntos
Microglia/fisiologia , Plasticidade Neuronal/fisiologia , Norepinefrina/fisiologia , Córtex Visual/fisiologia , Animais , Benzilaminas/farmacologia , Receptor 1 de Quimiocina CX3C/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Ritmo Circadiano/fisiologia , Clembuterol/farmacologia , Dexmedetomidina/farmacologia , Dominância Ocular , Feminino , Fentanila/farmacologia , Locus Cerúleo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Microglia/citologia , Microglia/efeitos dos fármacos , Nadolol/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Norepinefrina/metabolismo , Propanolaminas/farmacologia , Restrição Física/fisiologia , Terbutalina/farmacologia , Vigília , Ferimentos e Lesões/fisiopatologia
7.
Br J Anaesth ; 123(6): 827-838, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31623841

RESUMO

BACKGROUND: Spinal cord injury induces inflammatory responses that include the release of cytokines and the recruitment and activation of macrophages and microglia. Neuroinflammation at the lesion site contributes to secondary tissue injury and permanent locomotor dysfunction. Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is anti-inflammatory and neuroprotective in both preclinical and clinical trials. We investigated the effect of DEX on the microglial response, and histological and neurological outcomes in a rat model of cervical spinal cord injury. METHODS: Anaesthetised rats underwent unilateral (right) C5 spinal cord contusion (75 kdyne) using an impactor device. The locomotor function, injury size, and inflammatory responses were assessed. The effect of DEX was also studied in a microglial cell culture model. RESULTS: DEX significantly improved the ipsilateral upper-limb motor dysfunction (grooming and paw placement; P<0.0001 and P=0.0012), decreased the injury size (P<0.05), spared white matter (P<0.05), and reduced the number of activated macrophages (P<0.05) at the injury site 4 weeks post-SCI. In DEX-treated rats after injury, tissue RNA expression indicated a significant downregulation of pro-inflammatory markers (e.g. interleukin [IL]-1ß, tumour necrosis factor-α, interleukin (IL)-6, and CD11b) and an upregulation of anti-inflammatory and pro-resolving M2 responses (e.g. IL-4, arginase-1, and CD206) (P<0.05). In lipopolysaccharide-stimulated cultured microglia, DEX produced a similar inflammation-modulatory effect as was seen in spinal cord injury. The benefits of DEX on these outcomes were mostly reversed by an α2-adrenergic receptor antagonist. CONCLUSIONS: DEX significantly improves neurological outcomes and decreases tissue damage after spinal cord injury, which is associated with modulation of neuroinflammation and is partially mediated via α2-adrenergic receptor signaling.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Inflamação/tratamento farmacológico , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Microglia/efeitos dos fármacos , Ratos , Ratos Long-Evans , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologia
8.
Life Sci ; 236: 116921, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610196

RESUMO

AIMS: To assess the role of glycogen synthase kinase-3ß (GSK3ß) and ß-catenin in the protection of ischemic injury by dexmedetomidine (Dex). MAIN METHODS: Adult male Sprague-Dawley rats were subjected to (middle cerebral artery occlusion, MCAO) for 2 h followed by reperfusion and Dex was administered 30min before MCAO. The neurological deficit score, cerebral infarct size and neuron survival were evaluated at 24 h after reperfusion. The expression of pAKT, pGSK3ß and ß-catenin in the ischemic penumbra was assayed by Western blot at 2 h after reperfusion. KEY FINDINGS: We found that the Dex-induced increment of neuron survival in the ischemic penumbra was diminished by the PI3K inhibitor LY294002 and the ß-catenin inhibitor XAV939, respectively. The increasing expression of pAKT, pGSK3ß and ß-catenin induced by Dex was markedly inhibited by LY294002. And the increasing expression of ß-catenin in nuclei induced by Dex was markedly inhibited by XAV939. At the same time, the GSK3ß inhibitor SB216763 also caused an increment of neuron survival and an increasing expression of pGSK3ß and ß-catenin in the ischemic penumbra. SIGNIFICANCE: Our data suggested that treatment with Dex reduced cerebral injury in rats exposed to cerebral ischemia-reperfusion (I/R) by the activation of the PI3K/AKT/GSK3ß pathways as well the activation of downstream Wnt/ß-catenin pathway. And the Wnt/ß-catenin pathway may play an important role in the protection against cerebral ischemia/reperfusion injury in rats.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Infarto da Artéria Cerebral Média/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteínas Wnt/genética , beta Catenina/genética
9.
Am J Vet Res ; 80(10): 912-922, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556714

RESUMO

OBJECTIVE: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS: 8 purpose-bred, 2-year-old Beagles. PROCEDURES: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 µg/kg) or MED mixed with 400 µg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 µg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Cães , Hipnóticos e Sedativos/farmacologia , Imidazóis/farmacologia , Medetomidina/farmacologia , Quinolizinas/farmacologia , Anestesia/veterinária , Animais , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Injeções Intramusculares/veterinária , Masculino , Medetomidina/administração & dosagem , Medetomidina/antagonistas & inibidores , Quinolizinas/antagonistas & inibidores , Distribuição Aleatória , Método Simples-Cego
10.
Med Sci Monit ; 25: 6782-6787, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498783

RESUMO

BACKGROUND This study aimed to investigate effects of intra-operative administration with dexmedetomidine (Dex) on hemodynamics and renal function in patients with malignant obstructive jaundice. MATERIAL AND METHODS Our randomized, double-blinded, placebo-controlled study was conducted among 40 patients with malignant obstructive jaundice between August 2009 and March 2011 in The Affiliated Hospital of Inner Mongolia Medical University. The 40 patients were randomly divided into 2 groups: the Dex group (receiving Dex 0.5 µg/kg 10-minutes before induction and then a 0.5 µg/kg/hour maintenance infusion until end of operation 30 minutes) and the Control group (receiving normal saline of same amount and at same rate). The adverse events, including incidence of cardiovascular complications and nausea and vomiting, and length of hospital stay were determined. The level of cystatin C (CysC), retinol-binding protein (RBP), creatinine (Scr), and blood urea nitrogen (BUN) were also evaluated. RESULTS Dexmedetomidine administration significantly decreased heart rate (HR) and stroke volume variation (SVV) and significantly increased capital venous pressure (CVP) and mean arterial pressure (MAP) values compared to that in the Control group (P<0.05). Dexmedetomidine administration significantly upregulated urine volume and significantly downregulated atropine levels compared to the Control group (P<0.05). Dexmedetomidine administration significantly improved renal functions, by modulating CysC, RBP, Scr and BUN levels compared to the Control group (P<0.05). Dexmedetomidine administration demonstrated no additional side-effects. Dexmedetomidine administration significantly shortened length of hospitalization in the Dex group compared to the Control group (P<0.05). CONCLUSIONS Dexmedetomidine plays preventive effects on renal dysfunction and hemodynamic stability in malignant obstructive jaundice patients during peri-operative period.


Assuntos
Dexmedetomidina/uso terapêutico , Hemodinâmica , Icterícia Obstrutiva/fisiopatologia , Icterícia Obstrutiva/cirurgia , Rim/fisiopatologia , Atropina/urina , Transfusão de Sangue , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Micção/efeitos dos fármacos
11.
Medicine (Baltimore) ; 98(33): e16772, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415378

RESUMO

BACKGROUND: Pneumoperitoneum and steep Trendelenburg position during robot-assisted laparoscopic prostatectomy (RALP) can increase intracranial pressure (ICP). Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, can cause cerebral vasoconstriction and decrease cerebral blood flow by stimulating the postsynaptic alpha-2 adrenergic receptors on cerebral blood vessels. However, the effects of dexmedetomidine on ICP are controversial and have not been evaluated during RALP under the establishment of pneumoperitoneum in the steep Trendelenburg position. Therefore, we evaluated the effect of dexmedetomidine on optic nerve sheath diameter (ONSD) as a surrogate for assessing ICP during RALP. METHODS: Patients were randomly allocated to receive dexmedetomidine (n = 63) (loading dose, 1 µg/kg for 10 minutes and continuous infusion, 0.4 µg/kg/hr) or normal saline (n = 63). The ONSD was measured at 10 minutes after induction of anesthesia in the supine position (T1), 30 minutes (T2) and 60 minutes (T3) after establishment of pneumoperitoneum in the steep Trendelenburg position, and at closing the skin in the supine position (T4). Hemodynamic and respiratory variables were measured at every time point. RESULTS: ONSDs at T2, T3, and T4 were significantly smaller in the dexmedetomidine group than in the control group (5.26 ±â€Š0.25 mm vs 5.71 ±â€Š0.26 mm, 5.29 ±â€Š0.24 mm vs 5.81 ±â€Š0.23 mm, and 4.97 ±â€Š0.24 mm vs 5.15 ±â€Š0.28 mm, all P <.001). ONSDs at T2, T3, and T4 were significantly increased compared to T1 in both groups. Hemodynamic and respiratory variables, except heart rate, did not significantly differ between the 2 groups. The bradycardia and atropine administration were not significantly different between the 2 groups. CONCLUSION: Dexmedetomidine attenuates the increase of ONSD during RALP, suggesting that intraoperative dexmedetomidine administration may effectively attenuate the ICP increase during pneumoperitoneum in the Trendelenburg position.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Hipertensão Intracraniana/prevenção & controle , Pressão Intracraniana/efeitos dos fármacos , Nervo Óptico/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Idoso , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Período Intraoperatório , Laparoscopia , Masculino , Nervo Óptico/diagnóstico por imagem , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Resultado do Tratamento
12.
Am J Vet Res ; 80(9): 878-884, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449443

RESUMO

OBJECTIVE: To evaluate the effects of injectable dexmedetomidine-ketamine-midazolam (DKM) and isoflurane inhalation (ISO) anesthetic protocols on selected ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus; BTPDs). ANIMALS: 9 zoo-kept BTPDs. PROCEDURES: The BTPDs received dexmedetomidine hydrochloride (0.25 mg/kg, IM), ketamine hydrochloride (40 mg/kg, IM), and midazolam hydrochloride (1.5 mg/kg, IM) or inhalation of isoflurane and oxygen in a randomized complete crossover design (2-day interval between anesthetic episodes). Pupil size, globe position, tear production, and intraocular pressure measurements were recorded at 5, 30, and 45 minutes after induction of anesthesia. For each BTPD, a phenol red thread test was performed in one randomly selected eye and a modified Schirmer tear test I was performed in the other eye. Intraocular pressure was measured by rebound tonometry. RESULTS: Compared with findings for the DKM protocol, pupil size was smaller at all time points when the BTPDs underwent the ISO protocol. Globe position remained central during anesthesia with the DKM protocol, whereas it varied among central, ventromedial, and ventrolateral positions during anesthesia with the ISO protocol. Tear production and intraocular pressure decreased significantly over time when the BTPDs underwent either protocol. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ophthalmic examination findings for anesthetized BTPDs can be influenced by the anesthetic protocol used. The DKM protocol may result in more consistent pupil size and globe position, compared with that achieved by use of the ISO protocol. Tear production and intraocular pressure measurements should be conducted promptly after induction of anesthesia to avoid the effect of anesthetic episode duration on these variables.


Assuntos
Anestesia/veterinária , Anestésicos Inalatórios/farmacologia , Olho/efeitos dos fármacos , Sciuridae , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/farmacologia , Animais , Animais de Zoológico , Dexmedetomidina/farmacologia , Pressão Intraocular/efeitos dos fármacos , Isoflurano/farmacologia , Ketamina/farmacologia , Masculino , Midazolam/farmacologia , Lágrimas/efeitos dos fármacos
13.
J Craniofac Surg ; 30(8): 2469-2472, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469734

RESUMO

INTRODUCTION: Flap surgery is one of the most commonly used techniques of reconstructive surgery for effective repair of damaged tissue. Optimal anesthetic technique and anesthetic agent plays an important role in flap perfusion. This study aimed to evaluate the effects of dexmedetomidine infusion on the microcirculation in the cremaster muscle flap by direct in vivo monitoring. MATERIALS AND METHODS: We randomly divided 9 Wistar albino rats into 3 groups. The rats in the control group underwent the surgical procedure (isolation of the cremaster muscle) alone; the rats in the experimental groups 1 and 2 received an infusion of dexmedetomidine (10 and 30 min) after the surgical procedure. RESULTS: The means of vessel diameters, number of functional capillaries, and movements of leukocytes in all groups were evaluated using intravital microscopic examination. The diameters of the arterioles and venules of the cremaster muscle significantly increased in the dexmedetomidine groups. The number of functional capillaries was higher in the dexmedetomidine groups than in the control group. No difference was observed in the movements of leukocytes between the control and experimental groups. Dexmedetomidine significantly increased the diameters of the arterioles and venules of the cremaster flap and the number of functional capillaries. CONCLUSION: On the basis of the effects of dexmedetomidine on microcirculation, we suggest that dexmedetomidine continue to be used as an anesthetic agent, and may be considered also for reconstructive procedures, particularly flap surgery.


Assuntos
Anestésicos/farmacologia , Dexmedetomidina/farmacologia , Músculos Abdominais , Animais , Capilares , Leucócitos , Microcirculação , Ratos , Ratos Wistar , Retalhos Cirúrgicos
14.
Life Sci ; 232: 116611, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260683

RESUMO

PURPOSE: To observe the effect of dexmedetomidine (DEX) on mitochondrial apoptosis of hippocampal neurons in hypoxia/reoxygenation (H/R) brain injury in developing rats, and to investigate its regulatory mechanism on HIF-1α/p53 signaling pathway. METHODS: Hypoxia/reoxygenation model was used in this study. TUNEL assay was performed to detect cell apoptosis. Immunohistochemical analysis and Western-blotting analysis were conducted to detect Cytochrome-C (Cyt-c), APAF-1, Caspase-3, Neuroglobin (Ngb), HIF-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed. RESULTS: 50 µg/kg DEX improved H/R-induced brain injury and inhibited mitochondrial apoptosis in rats. Western-blotting and Immunohistochemical results demonstrated that DEX could up-regulate Ngb through α2 receptor to inhibit H/R-induced mitochondrial apoptosis. In addition, by adding inhibitors yohimbine and 2-methoxyestradiol (2ME2), we found that DEX could activate HIF-1α/p53 signaling pathway. MWM test showed that DEX could enhance long-term learning and memory of H/R brain injury rats. CONCLUSION: DEX alleviates H/R-induced brain injury and mitochondrial apoptosis in developing rats through α2 receptor, which may be related to activation of HIF-1α/p53 signaling pathway to up-regulate the expression of Ngb.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Dexmedetomidina/farmacologia , Hipocampo/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neurônios/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Hipocampo/metabolismo , Hipocampo/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/efeitos dos fármacos
15.
Artigo em Chinês | MEDLINE | ID: mdl-31262103

RESUMO

Objective: To compare the parameters of polysomnography (PSG) in sleep structure and respiratory events between dexmedetomidine-induced sleep and natural sleep. Methods: From April 2016 to September 2018, a total of 44 patients with obstructive sleep apnea (OSA) and 3 patients with simple snoring completed PSG monitor both in natural sleep and dexmedetomidine-induced sleep in Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tsinghua Changgung Hospital. The PSG parameters were statistically analysed with SPSS 22.0 software. Results: The average dose of dexmedetomidine was (104.60±27.93) µg, and there was no significant difference between the induced-sleep efficiency and the natural sleep efficiency (82.14%±16.66% vs. 86.50%±9.18%, t=-1.559, P>0.05). There was no rapid eye movement(REM) stages in all 47 subjects and only 1 case of them had non-rapid eye movement(NREM) stage 3 in induced sleep. The percentage of NREM1 in total sleep time was statistically different between the two groups (42.10%±26.71% vs. 17.47%±11.68%, t=5.997, P<0.001),but there was no significant difference in the percentage of NREM2 in total sleep time between the two groups (56.96%±26.0% vs. 62.95%±9.03%, t=-1.521, P=0.135). About respiratory events, there were significant differences in apnea hypopnea index ((46.29±20.23)/h vs. (39.67±25.41)/h), obstructive apnea index (25.20[10.50,45.40]/h vs. 16.20[3.30,35.20]/h) between induced-sleep and natural sleep (t=2.297, Z=-3.008, all P<0.05), these difference were more significant in mild-to-moderate OSA. There were no statistically significant differences in central apnea index (0.00[0.00,2.80]/h vs. 0.40[0.10,1.20]/h), mixed apnea index (0.00[0.00,6.20]/h vs. 0.00[0.00,3.40]/h, hypopnea index (4.20[0.00,3.30]/h vs. 12.00[5.20,17.40]/h), Z=-0.110,-0.508,-1.544, all P>0.05). There were statistical differences in the lowest oxygen saturation (84.77%±7. 59% vs. 80.21%±11.62%, t=2.558, P=0.014). Conclusions: There is no significant difference in sleep efficiency and NREM2 between dexmedetomidine induced sleep and natural sleep.NREM3 sleep is rare induced, but REM sleep is none of all. And dexmedetomidine induced sleep may aggravate obstructive sleep apnea, but not central apnea.


Assuntos
Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Sono , Ronco/fisiopatologia , Humanos , Respiração/efeitos dos fármacos , Sono/efeitos dos fármacos , Sono/fisiologia
16.
Anticancer Res ; 39(7): 3519-3529, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262876

RESUMO

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Catalase/farmacologia , Células Cultivadas , Criança , Clonidina/farmacologia , Fragmentação do DNA , Dexmedetomidina/farmacologia , Epinefrina/farmacologia , Humanos , Isoproterenol/farmacologia , Fenilefrina/farmacologia , Superóxido Dismutase/farmacologia
17.
Drug Des Devel Ther ; 13: 2067-2079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308624

RESUMO

Background: Understanding of lidocaine-induced neurotoxicity is not complete, resulting in the unsuccessful treatment in some clinical settings. Dexmedetomidine (DEX) has been shown to alleviate lidocaine-induced neurotoxicity in our previous cell model. However, the rationale for DEX combined with lidocaine to reduce lidocaine-induced neurotoxicity in the clinical setting remains to be further clarified in the detailed molecular mechanism. Methods: In this study, we established a cellular injury model by lidocaine preconditioning. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay kit were used to analyze cell proliferation. Cell apoptosis was measured by flow cytometry and Hoechst 33342 staining. Cell cycle progression was detected by flow cytometry. The protein expression levels were detected by Western blotting and immunofluorescence staining. Results: Our results showed that DEX dose-dependently restored impaired proliferation of PC12 cells induced by lidocaine,as reflected by the increased cell viability and EdU positive cells, which were consistent with the decreased expression of tumor suppressor protein p21 and increased expression of cell cycle-related cyclin D1 and CDK1. In addition, DEX dose-dependently reduced apoptotic PC12 cells induced by lidocaine,as reflected by the decreased expression of apoptosis-related Bax, caspase-3 and caspase-9 and increased expression of anti-apoptotic Bcl-2 compared to the cells only treated with lidocaine. Mechanistically, with gain-or-loss-of-function of STMN1, we showed that DEX-mediated neuroprotection by lidocaine-induced damage is associated with downregulation of STMN1 which might be an upstream molecule involved in regulation of mitochondria death pathway. Conclusion: Our results reveal that DEX is likely to be an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.


Assuntos
Dexmedetomidina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Lidocaína/farmacologia , Substâncias Protetoras/farmacologia , Estatmina/biossíntese , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Lidocaína/antagonistas & inibidores , Células PC12 , Ratos
18.
Vet Anaesth Analg ; 46(4): 421-428, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178412

RESUMO

OBJECTIVE: To investigate alfaxalone total intravenous anaesthesia (TIVA) following premedication with methadone combined with acepromazine (ACP) or dexmedetomidine in bitches undergoing ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 female Beagles. METHODS: Dogs were premedicated intravenously with methadone (0.2 mg kg-1) combined with ACP (20 µg kg-1, group AM) or dexmedetomidine (5 µg kg-1, group DM). Anaesthesia was induced with alfaxalone (2 mg kg-1). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 and adjusted every 5 minutes based on clinical assessment. Mechanical ventilation was initiated when necessary to maintain normocapnia. Anaesthetic monitoring included electrocardiogram, heart rate (HR), invasive diastolic (DAP), systolic (SAP) and mean arterial blood pressure, arterial haemoglobin oxygen saturation, respiratory variables and oesophageal temperature. Data were recorded every 5 minutes. A mixed model statistical approach was used to compare cardiovascular variables within and between groups (α = 0.05). A Wilcoxon rank-sum test was used to compare body temperature, VRI alfaxalone rate, administered rescue analgesia, sedation, induction, intubation, recovery scores and recovery times between treatments. RESULTS: Overall HR, SAP and DAP differed between groups (p = 0.001, 0.016, 0.019, respectively). The mean VRI dose rate of alfaxalone differed between groups DM [0.13 (0.11-0.14) mg kg-1 minute-1] and AM [0.18 (0.13-0.19) mg kg-1 minute-1; p = 0.030]. Rescue analgesia was administered more in group AM (p = 0.019). No significant difference in recovery times and scores was observed between protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone TIVA following dexmedetomidine/methadone premedication produced a more stable plane of anaesthesia to perform ovariohysterectomy than ACP/methadone. A dose reduction of alfaxalone of 27.7% was obtained in group DM compared with group AM. Recovery quality and recovery times were comparable between both groups.


Assuntos
Acepromazina/farmacologia , Dexmedetomidina/farmacologia , Cães , Pregnanodionas/farmacologia , Pré-Medicação , Acepromazina/administração & dosagem , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Dexmedetomidina/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacologia , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Histerectomia/veterinária , Metadona , Ovariectomia/veterinária , Pregnanodionas/administração & dosagem , Distribuição Aleatória
19.
Vet Anaesth Analg ; 46(4): 476-482, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178413

RESUMO

OBJECTIVE: To determine if the combinations of morphine, dexmedetomidine and maropitant enhance the analgesic effect and decrease the dose of individual drugs in rats subjected to noxious thermal stimulation with hot-plate and tail-flick tests. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: A total of 96 male Sprague-Dawley rats. METHODS: The rats were randomly assigned to the following groups: 1) morphine (3 mg kg-1; Mor); 2) dexmedetomidine (10 µg kg-1; Dex); 3) maropitant (20 mg kg-1; Maro); 4) morphine (1.5 mg kg-1) + dexmedetomidine (5 µg kg-1; Mor + Dex); 5) dexmedetomidine (5 µg kg-1) + maropitant (10 mg kg-1; Dex + Maro); 6) morphine (1.5 mg kg-1) + maropitant (10 mg kg-1; Mor + Maro); 7) morphine (1 mg kg-1) + dexmedetomidine (3.5 µg kg-1) + maropitant (6.5 mg kg-1; Mor + Dex + Maro); and 8) normal saline (0.5 mL; saline), all injected intravenously. The tail-flick and hot-plate tests were performed before and 5, 15, 30, 45, 60, 90 and 120 minutes after the injection of the drugs. These variables were analysed with the effect-time area under the curve (AUC) analysis and a mixed linear model. RESULTS: Data were analysed in 94 rats. The rank order of the total analgesic effects of the treatment groups shown by AUC analysis was found to be Mor > Maro + Mor > Dex + Mor > Dex > Maro > Dex + Maro + Mor > Dex + Maro > saline for the hot-plate test, and Maro + Mor > Mor > Dex + Mor > Dex + Maro + Mor > Maro > Dex > Dex + Maro > saline for the tail-flick test. The mixed model analysis showed a significant difference between latencies of the group morphine + maropitant versus all other treatment groups in the tail-flick test (p < 0.0001) and morphine versus saline in the hot-plate test (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Morphine and maropitant appeared to show a supra-additive effect for analgesia in the tail-flick test. Clinical trials should be conducted to establish its use in treating pain.


Assuntos
Dexmedetomidina/farmacologia , Morfina/farmacologia , Medição da Dor/veterinária , Dor/tratamento farmacológico , Quinuclidinas/farmacologia , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Animais , Antieméticos/administração & dosagem , Antieméticos/farmacologia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacocinética , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Morfina/administração & dosagem , Morfina/farmacocinética , Quinuclidinas/administração & dosagem , Quinuclidinas/farmacocinética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
20.
J Zhejiang Univ Sci B ; 20(7): 598-604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168973

RESUMO

There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α2A-adrenergic receptor (ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 µg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after intravenous infusion of dexmedetomidine.


Assuntos
Bradicardia/induzido quimicamente , Dexmedetomidina/farmacologia , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos alfa 2/genética , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Adulto , Pressão Sanguínea , China , Dexmedetomidina/administração & dosagem , Feminino , Genótipo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Farmacogenética , Análise de Sequência de DNA
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