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1.
Am J Vet Res ; 82(11): 858-864, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34669493

RESUMO

OBJECTIVE: To evaluate the effects of a dexmedetomidine-midazolam-ketamine (DMK) combination administered IM to captive red-footed tortoises (Chelonoidis carbonaria). ANIMALS: 12 healthy adult red-footed tortoises. PROCEDURES: In a prospective experimental study, DMK (0.1, 1.0, and 10 mg/kg, respectively) was administered IM as separate injections into the right antebrachium. Atipamezole (0.5 mg/kg, IM) and flumazenil (0.05 mg/kg, SC) were administered into the left antebrachium 60 minutes later. Times to the first treatment response and maximal treatment effect after DMK administration and time to recovery after reversal agent administration were recorded. Vital signs and reflexes or responses to stimuli were assessed and recorded at predetermined intervals. RESULTS: DMK treatment produced deep sedation or light anesthesia for ≥ 20 minutes in all tortoises. Induction and recovery were rapid, with no complications noted. Median times to first response, maximum effect, and recovery were 4.5, 35, and 14.5 minutes, respectively. Two tortoises required additional reversal agent administration but recovered < 20 minutes after the repeated injections. Mean heart and respiratory rates decreased significantly over time. All animals lost muscle tone in the neck and limbs from 35 to 55 minutes after DMK injection, but other variables including palpebral reflexes, responses to mild noxious stimuli (eg, toe pinching, tail pinching, and saline ([0.9 NaCl] solution injection), and ability to intubate were inconsistent. CONCLUSIONS AND CLINICAL RELEVANCE: DMK administration produced deep sedation or light anesthesia with no adverse effects in healthy adult red-footed tortoises. At the doses administered, deep surgical anesthesia was not consistently achieved. Anesthetic depth must be carefully evaluated before performing painful procedures in red-footed tortoises with this DMK protocol.


Assuntos
Dexmedetomidina , Ketamina , Tartarugas , Animais , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Midazolam/farmacologia , Estudos Prospectivos
2.
J Zoo Wildl Med ; 52(3): 1009-1012, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34687517

RESUMO

This study compared dexmedetomidine or xylazine in combination with tiletamine-zolazepam for chemical immobilization of wild fallow deer (Dama dama) in a prospective, randomized, blinded clinical study. Forty fallow deer were divided into two groups: tiletamine-zolazepam-xylazine (TZX) and tiletamine-zolazepam-dexmedetomidine (TZD). The TZX group was immobilized with 1.9 ± 0.05 mg/kg of xylazine and 1.48 ± 0.05 mg/kg of tiletamine-zolazepam, whereas the TZD group was immobilized with 34.15 ± 1.1 µg/kg of dexmedetomidine and 0.97 ± 0.03 mg/kg of tiletamine-zolazepam by dart. The induction time was recorded. During the immobilization, heart rate, respiratory rate, body temperature, hemoglobin oxygen saturation, blood lactate concentration, and quality of immobilization were recorded at 10, 20, and 30 m after drug administration. The time of achievement of sternal recumbency and that of standing were also recorded. The TZD group showed a significantly shorter induction time (8 ± 1.6 m, TZX group; 4 ± 0.5 m, TZD group), significantly higher quality of immobilization score (2[1-2], TZX group; 4[4-4], TZD group), and significantly lower lactate levels (5[3-7] mmol/L, TZX group; 2[1-3] mmol/L, TZD group). The time to sternal recumbency was 7 ± 1.6 m (TZX group) and 4 ± 0.5 m (TZD group), and time to quadrupedal standing was 20 ± 1.6 m (TZX group) and 16 ± 0.8 m (TZD group) (P = 0.001). Dexmedetomidine combined with tiletamine-zolazepam is a viable alternative to xylazine for the chemical immobilization of fallow deer.


Assuntos
Dexmedetomidina , Tiletamina , Anestésicos Dissociativos , Animais , Dexmedetomidina/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica/veterinária , Imobilização/veterinária , Estudos Prospectivos , Xilazina/farmacologia , Zolazepam
3.
J Zoo Wildl Med ; 52(3): 1018-1023, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34687519

RESUMO

This study is aimed at evaluating the efficacy of two protocols for the immobilization of mouflon (Ovis orientalis musimon). Six mouflon were immobilized twice using IM medetomidine 0.07 ± 0.01 mg/kg, ketamine 2.88 ± 0.48 mg/kg, and morphine 0.57 ± 0.09 mg/kg (MKM) or dexmedetomidine 0.04 ± 0.01 mg/kg, ketamine 3.01 ± 0.6 mg/kg, and morphine 0.60 ± 0.12 mg/kg (DKM). Anesthetic times were recorded from injection to initial drug effects, sternal recumbency, lateral recumbency, unresponsiveness to external stimuli, and recovery following atipamezole IM administration. Cardiopulmonary variables (HR in beats/min, RR in breaths/min, mean, systolic, and diastolic noninvasive blood pressure [MAP, SAP, DAP] in mm Hg, oxygen hemoglobin saturation [SpO2)], expired end tidal carbon dioxide [PECO2]), and rectal temperature in °C were monitored and recorded. No statistically significant differences were detected between protocols at any time point and no significant differences were detected in any measured variables at any time point between protocols. However, a significant decrease in the noninvasive blood pressure variables (SAP, MAP, and DAP) and in the RR were detected over time. Both chemical immobilization protocols provided at least 50 min of immobilization in mouflon, allowing minor procedures and tracheal intubation.


Assuntos
Dexmedetomidina , Ketamina , Anestésicos Dissociativos/farmacologia , Animais , Dexmedetomidina/farmacologia , Frequência Cardíaca , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Ketamina/farmacologia , Medetomidina/farmacologia , Morfina/farmacologia , Carneiro Doméstico
4.
Can J Vet Res ; 85(4): 251-260, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34602729

RESUMO

Neonatal foals may require prolonged sedation to permit ventilatory support in the first few days of life. The objective of this study was to evaluate and compare the cardiopulmonary effects and clinical recovery characteristics of 2 sedative/analgesia protocols in healthy foals receiving assisted ventilation. Foals were randomized to receive dexmedetomidine, butorphanol, and propofol (DBP) or midazolam, butorphanol, and propofol (MBP) during a 24-hour period. Infusion rates of dexmedetomidine, midazolam, and propofol were adjusted and propofol boluses administered according to set protocols to maintain optimal sedation and muscle relaxation. Ventilatory support variables were adjusted to preset targets. Physiologic variables were recorded, cardiac output (CO) measured (thermodilution), and arterial and mixed venous blood collected for gas analysis at intervals up to 24 hours. Foals in group DBP received dexmedetomidine [2.4 ± 0.5 µg/kg body weight (BW) per hour], butorphanol (13 µg/kg BW per hour), and propofol (6.97 ± 0.86 mg/kg BW per hour), whereas foals in group MBP received midazolam (0.14 ± 0.04 mg/kg BW per hour), butorphanol (13 µg/kg BW per hour), and propofol (5.98 ± 1.33 mg/kg BW per hour). Foals in the DBP group received significantly more propofol boluses (9.0 ± 3.0) than those in the MBP group (4.0 ± 2.0). Although physiologic variables remained within acceptable limits, heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI) were lower in foals in the DBP group than in the MBP group. Times to sternal recumbency, standing, and nursing were significantly shorter in the DBP than MBP group. We found that MBP and DBP protocols are suitable to assist ventilatory support in neonatal foals, although MBP results in a prolonged recovery compared to DBP.


Assuntos
Período de Recuperação da Anestesia , Frequência Cardíaca/efeitos dos fármacos , Cavalos/fisiologia , Hipnóticos e Sedativos/farmacologia , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Animais , Animais Recém-Nascidos/fisiologia , Butorfanol/administração & dosagem , Butorfanol/farmacologia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Quimioterapia Combinada , Feminino , Hipnóticos e Sedativos/administração & dosagem , Masculino , Midazolam/administração & dosagem , Midazolam/farmacologia , Propofol/administração & dosagem , Propofol/farmacologia , Respiração Artificial
5.
Braz J Anesthesiol ; 71(5): 489-497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34537120

RESUMO

BACKGROUND: Spinal anesthesia is commonly employed during inguinal hernial surgeries. Its short duration may, however, be considered a limitation, especially for bilateral hernial repair. The aim of this research is to investigate the analgesic and hemodynamic effects of intravenous infusion of both MgSO4 and dexmedetomidine on patients undergoing bilateral inguinal hernia surgeries under spinal anesthesia. METHODS: This study was a prospective, randomized, double-blinded controlled trail. It included 60 male patients who had been scheduled for bilateral elective inguinal hernia surgery under spinal anesthesia at Kasr Al-Aini hospital. Patients were randomly allocated to one of three groups (n = 20 each) to receive 50 mL of 0.9% saline intravenous infusion of either dexmedetomidine 0.5 µg.kg-1. h-1 (Group D) or magnesium sulphate 15 mg.kg-1. h-1 (Group M) or normal saline (Group S). The primary outcome of this study was set as the total duration of analgesia. Secondary outcomes were set as the onset and duration of sensory and motor blockade, perioperative hemodynamics, and the total 24-hour postoperative morphine consumption. RESULTS: Durations of sensory and motor blockades as well as durations of analgesia were all significantly longer among patients in Group D (mean 2.2, 3.5, 5.8 hours respectively) and Group M (mean 2.2, 3.3, 5.2 hours respectively), in comparison to Group S (mean 1.5, 2.7, 3.9 hours respectively). No significant differences were found in systolic or diastolic arterial blood pressure, heart rate oxygen saturation, cardiac output, or stroke volume among the study groups. Seven patients in Group D and four patients in Groups M and S developed hypotension. CONCLUSION: Intravenous infusion of either dexmedetomidine or MgSO4 with spinal anesthesia effectively improves the quality of spinal anesthesia and prolongs the duration of postoperative analgesia and decreases the 24-hour postoperative morphine consumption. Results also demonstrated that the use of dexmedetomidine resulted in a slightly longer duration of analgesia, whilst the use of MgSO4 resulted in slightly better hemodynamic stability.


Assuntos
Raquianestesia , Dexmedetomidina , Hérnia Inguinal , Analgésicos/uso terapêutico , Dexmedetomidina/farmacologia , Método Duplo-Cego , Hemodinâmica , Hérnia Inguinal/cirurgia , Humanos , Infusões Intravenosas , Sulfato de Magnésio/farmacologia , Masculino , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos
6.
Eur J Neurosci ; 54(9): 7006-7047, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34561931

RESUMO

Neurological disorders following brain injuries and neurodegeneration are on the rise worldwide and cause disability and suffering in patients. It is crucial to explore novel neuroprotectants. Dexmedetomidine, a selective α2-adrenoceptor agonist, is commonly used for anxiolysis, sedation and analgesia in clinical anaesthesia and critical care. Recent studies have shown that dexmedetomidine exerts protective effects on multiple organs. This review summarized and discussed the current neuroprotective effects of dexmedetomidine, as well as the underlying mechanisms. In preclinical studies, dexmedetomidine reduced neuronal injury and improved functional outcomes in several models, including hypoxia-induced neuronal injury, ischaemic-reperfusion injury, intracerebral haemorrhage, post-traumatic brain injury, anaesthetic-induced neuronal injury, substance-induced neuronal injury, neuroinflammation, epilepsy and neurodegeneration. Several mechanisms are associated with the neuroprotective function of dexmedetomidine, including neurotransmitter regulation, inflammatory response, oxidative stress, apoptotic pathway, autophagy, mitochondrial function and other cell signalling pathways. In summary, dexmedetomidine has the potential to be a novel neuroprotective agent for a wide range of neurological disorders.


Assuntos
Dexmedetomidina , Fármacos Neuroprotetores , Dexmedetomidina/farmacologia , Humanos , Mitocôndrias , Neurônios/metabolismo , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
7.
Acta Anaesthesiol Scand ; 65(10): 1447-1456, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34368946

RESUMO

INTRODUCTION: Dexmedetomidine has been suggested to be a promising sedative for patients with Covid-19 infection (CV19). However, use of dexmedetomidine is limited by its heart rate (HR) and arterial blood pressure lowering effects. Moreover, CV19 is associated with cardiac manifestations including bradyarrythmias. The hemodynamic effects of dexmedetomidine have not been previously studied in CV19 patients. We evaluated the effects of dexmedetomidine on hemodynamic and respiratory parameters of CV19 patients. METHODS: In this single center study, all CV19 patients receiving dexmedetomidine for sedation during a one year period were included. Our primary outcomes included changes in HR, mean arterial pressure (MAP), respiratory rate (RR), partial oxygen pressure of arterial blood/fraction of inspired oxygen-ratio (PF-ratio), and Richmond Agitation and Sedation Score (RASS) during dexmedetomidine administration. RESULTS: We identified 39 patients with a mean (SD) age of 58.3 (12.7) years. After initiation of dexmedetomidine, HR decreased by 16.9 (3.3) beats/min (95% CI 9.5-22.4; p < 0.001). During the 12-hour follow-up period, HR decrease was significant at 2 to 12 h. Incident bradycardia (<45/min) was reported in 12 (30.8%) patients and it was associated with lower plasma C-reactive protein, Pro-calcitonin, and troponin T levels. There was no change in MAP compared to baseline. Dexmedetomidine administration was associated with improvement of PF-ratio (p < 0.001) and with decrease of RASS (p = 0.004). CONCLUSIONS: Dexmedetomidine is an effective sedative for CV19 patients and may improve their oxygenation. However, dexmedetomidine administration is associated with marked decline in HR and with a high incidence of bradycardia in patients with CV19.


Assuntos
COVID-19 , Dexmedetomidina , Estado Terminal , Dexmedetomidina/farmacologia , Hemodinâmica , Humanos , Hipnóticos e Sedativos/farmacologia , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2
8.
Biomed Res Int ; 2021: 3725316, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414234

RESUMO

Dexmedetomidine is an α2 adrenergic receptor agonist that has been reported to modulate the polarization of CD4+ T cells. However, the underlying mechanisms by which dexmedetomidine induces T-helper 1 (Th1) cell differentiation remain poorly understood. The aim of this study was to explore the potential mechanisms through which dexmedetomidine can induce Th1 cell differentiation. Purified CD4+ T cells were stimulated with anti-CD3/anti-CD28 and then treated with dexmedetomidine. Flow cytometry analysis was adopted to measure the concentration of Th1 cells. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR) were performed to detect protein levels and mRNA expression, respectively, of IFN-γ and IL-4. Western blotting was used to determine the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and T-bet expression. The Th1 cell subset and IFN-γ levels were elevated in the dexmedetomidine-induced CD4+ T cells. Dexmedetomidine enhanced the phosphorylation of STAT1 and the expression of T-bet in the CD4+ T cells. Atipamezole (an α2 adrenergic antagonist) and fludarabine (a STAT1 inhibitor) reversed the dexmedetomidine-induced Th1 cell differentiation. These results suggested that dexmedetomidine induced Th1 cell differentiation via the STAT1-T-bet signaling pathway.


Assuntos
Linfócitos T CD4-Positivos/citologia , Dexmedetomidina/farmacologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Th1/citologia , Animais , Anticorpos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas com Domínio T/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/metabolismo
9.
BMC Psychiatry ; 21(1): 408, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404384

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is an effective therapy for psychiatric disorders, but is associated with acute hyperdynamic responses including transient hypertension and tachycardia. This study aimed to assess the effectiveness of premedication with dexmedetomidine for hemodynamic attenuation after ECT and to evaluate its effects on seizure duration, postictal asystole duration, post ECT agitation and recovery time. METHODS: Twenty-four psychiatric patients who underwent a total of 72 ECT sessions (three sessions per patient) were randomly allocated to receive either dexmedetomidine 0.5 mcg/kg intravenous, dexmedetomidine 1 mcg/kg intravenous, or saline (control group) 15 min before the first ECT session. The patients subsequently received the other two premedication options for their next two ECT sessions. Blood pressure and heart rate were recorded at 5, 10, and 15 min after drug infusion and at 2.5, 5, 7.5, 10, 15, 20, 25, and 30 min after ECT. Asystole duration, seizure duration, post ECT agitation and recovery times were also recorded. RESULTS: The baseline characteristics were similar between the groups. Systolic blood pressure in both dexmedetomidine groups was significantly lower than that in the control group after ECT (p = 0.002). Diastolic blood pressure and heart rate were significantly lower in the dexmedetomidine 1 mcg/kg group (p = 0.002 and p = 0.013, respectively) compared with the control group. Asystole duration, seizure durations, post ECT agitation and recovery times were similar between the groups. CONCLUSIONS: Dexmedetomidine 1 mcg/kg administered 15 min before ECT attenuated the hemodynamic response, including suppressing the systolic, diastolic and heart rate increases, during ECT without affecting recovery time. It also did not prolong the post-stimulus asystole duration. TRIAL REGISTRATION: TCTR20170715003 , registered at Thai Clinical Trials Registry (TCTR), principal investigator: Pattika Subsoontorn, date of registration: 15/07/2017.


Assuntos
Dexmedetomidina , Eletroconvulsoterapia , Pressão Sanguínea , Estudos Cross-Over , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Método Duplo-Cego , Humanos , Hipnóticos e Sedativos/uso terapêutico , Pré-Medicação
10.
Medicine (Baltimore) ; 100(32): e26962, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397949

RESUMO

BACKGROUND: Adjuvants to local anesthetics, such as nalbuphine and dexmedetomidine, can be used to improve the quality and duration of peripheral nerve block effects. Dexmedetomidine has been successfully used as an adjuvant of erector spinae plane block (ESPB) with ropivacaine in video-assisted thoracoscopic lobectomy surgeries (VATLS). This study aimed to compare the effects of nalbuphine and dexmedetomidine used as adjuvants to ropivacaine for ESPB in VATLS. METHODS: A total of 102 patients undergoing VATLS with ESPB were enrolled and randomized into 3 groups, each of which received a different adjuvant to ropivacaine. The visual analogue scale score, onset and duration of sensory block, use of patient-controlled analgesia (PCA), rate of rescue analgesia, duration of postoperative hospitalization, incidence of postoperative nausea and vomiting, and chronic pain were measured and observed. RESULTS: The visual analogue scale score, total PCA use, rate of rescue analgesia, and postoperative chronic pain in the ropivacaine with dexmedetomidine (RD), and ropivacaine with nalbuphine (RN) groups were lower than those in the ropivacaine (RC) group (P < .05). The duration of sensory block was longer and the first use of PCA occurred later in the RD and RN groups than they did in the RC group (P < .05). CONCLUSIONS: As an adjuvant to ropivacaine in ESPB, nalbuphine and dexmedetomidine are comparable in terms of the associated analgesia, sensory block duration, need for rescue analgesia, and incidence of chronic pain in patients after VATLS.


Assuntos
Dexmedetomidina/farmacologia , Nalbufina/farmacologia , Dor Pós-Operatória/terapia , Pneumonectomia/métodos , Ropivacaina/farmacologia , Cirurgia Torácica Vídeoassistida/métodos , Ultrassonografia de Intervenção/métodos , Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/farmacologia , Anestésicos Locais/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Músculos Paraespinais/inervação , Nervos Periféricos , Resultado do Tratamento
11.
Sci Rep ; 11(1): 16153, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373548

RESUMO

Recent animal studies have drawn concerns regarding most commonly used anesthetics and their long-term cytotoxic effects, specifically on the nervous tissue. It is therefore imperative that the search continues for agents that are non-toxic at both the cellular and behavioural level. One such agent appears to be dexmedetomidine (DEX) which has not only been found to be less neurotoxic but has also been shown to protect neurons from cytotoxicity induced by other anesthetic agents. However, DEX's effects on the growth and synaptic connectivity at the individual neuronal level, and the underlying mechanisms have not yet been fully resolved. Here, we tested DEX for its impact on neuronal growth, synapse formation (in vitro) and learning and memory in a rodent model. Rat cortical neurons were exposed to a range of clinically relevant DEX concentrations (0.05-10 µM) and cellular viability, neurite outgrowth, synaptic assembly and mitochondrial morphology were assessed. We discovered that DEX did not affect neuronal viability when used below 10 µM, whereas significant cell death was noted at higher concentrations. Interestingly, in the presence of DEX, neurons exhibited more neurite branching, albeit with no differences in corresponding synaptic puncta formation. When rat pups were injected subcutaneously with DEX 25 µg/kg on postnatal day 7 and again on postnatal day 8, we discovered that this agent did not affect hippocampal-dependent memory in freely behaving animals. Our data demonstrates, for the first time, the non-neurotoxic nature of DEX both in vitro and in vivo in an animal model providing support for its utility as a safer anesthetic agent. Moreover, this study provides the first direct evidence that although DEX is growth permissive, causes mitochondrial fusion and reduces oxygen reactive species production, it does not affect the total number of synaptic connections between the cortical neurons in vitro.


Assuntos
Dexmedetomidina/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Anestésicos/farmacologia , Anestésicos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dexmedetomidina/toxicidade , Feminino , Lobo Frontal/citologia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Dinâmica Mitocondrial/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
12.
Exp Cell Res ; 406(2): 112762, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352276

RESUMO

Keratinocyte growth factor (KGF)-2 has been highlighted to play a significant role in maintaining the endothelial barrier integrity in lung injury induced by ischemia-reperfusion (I/R). However, the underlying mechanism remains largely unknown. The aims of this study were to determine whether dexmedetomidine preconditioning (DexP) modulates pulmonary I/R-induced lung injury through the alteration in KGF-2 expression. In our I/R-modeled mice, DexP significantly inhibited pathological injury, inflammatory response, and inflammatory cell infiltration, while promoted endothelial barrier integrity and KGF-2 promoter activity in lung tissues. Bioinformatics prediction and ChIP-seq revealed that I/R significantly diminished the level of H3K4me3 modification in the KGF-2 promoter, which was significantly reversed by DexP. Moreover, DexP inhibited the expression of histone demethylase JMJD3, which in turn promoted the expression of KGF-2. In addition, overexpression of JMJD3 weakened the protective effect of DexP on lung injury in mice with I/R. Collectively, the present results demonstrated that DexP ameliorates endothelial barrier dysfunction via the JMJD3/KGF-2 axis.


Assuntos
Dexmedetomidina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Fator 10 de Crescimento de Fibroblastos/metabolismo , Histonas/química , Histona Desmetilases com o Domínio Jumonji/metabolismo , Lesão Pulmonar/prevenção & controle , Traumatismo por Reperfusão/complicações , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Permeabilidade da Membrana Celular , Endotélio Vascular/metabolismo , Fator 10 de Crescimento de Fibroblastos/química , Fator 10 de Crescimento de Fibroblastos/genética , Histona Desmetilases com o Domínio Jumonji/genética , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Regulação para Cima
13.
Anesthesiology ; 135(4): 633-648, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34270686

RESUMO

BACKGROUND: Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. METHODS: Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin-dependent protein kinase 2α-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg-1 · min-1 for 45 min, eight rats; high dose: 4.5 µg · kg-1 · min-1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg-1 · min-1 for 30 min, seven rats; high dose: 4 mg · kg-1 · min-1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. RESULTS: Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide - saline] during dexmedetomidine infusion = -6.06 [99% CI = -12.36 to -1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [-1.93, -0.87] dB, 99% CI = [-4.16 to -0.56, -1.62 to -0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [-20.06 to 14.14, -20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: -3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). CONCLUSIONS: These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic's molecular target.


Assuntos
Ritmo Delta/efeitos dos fármacos , Dexmedetomidina/farmacologia , Ácido Glutâmico , Ketamina/farmacologia , Neurônios/efeitos dos fármacos , Núcleos Parabraquiais/efeitos dos fármacos , Anestesia/métodos , Anestésicos Dissociativos/farmacologia , Animais , Proteínas de Ligação ao Cálcio/fisiologia , Ritmo Delta/fisiologia , Ácido Glutâmico/fisiologia , Hipnóticos e Sedativos/farmacologia , Masculino , Neurônios/fisiologia , Núcleos Parabraquiais/fisiologia , Ratos , Ratos Sprague-Dawley
14.
Iran J Med Sci ; 46(4): 263-271, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34305238

RESUMO

Background: Intrathecal additive drugs are becoming increasingly common in anesthesia practice. We aimed to evaluate the additive effects of dexmedetomidine on spinal anesthesia with sufentanil in patients undergoing lower abdominal or lower limb surgery. Methods: This double-blind randomized controlled trial was performed in Mashhad, Iran, between 2017 and 2018. Sixty patients undergoing lower abdominal or lower limb surgery were randomly divided to receive 15 mg of bupivacaine and 3 µg of sufentanil (control group; n=30) or 15 mg of bupivacaine, 3 µg of sufentanil, and 10 µg of dexmedetomidine (intervention group; n=30). Outcomes, comprised of the onset and regression of sensory and motor blocks, the duration of analgesia, analgesic use, hemodynamic parameters, and side effects, were assessed. The data were analyzed in the SPSS software (version 22), using different statistical tests. A P value of less than 0.05 was considered significant. Results: The times of sensory and motor blocks reaching T10 and Bromage 3, respectively, were significantly shorter, while the times of sensory and motor regressions to S1 and Bromage 0, correspondingly, were significantly longer in the intervention group than in the control group (P<0.001). Both the frequency (P=0.006) and the dose (P<0.001) of postoperative analgesic use were significantly lower, and the duration of analgesia was significantly longer in the intervention group (P<0.001). The frequency of side effects and changes in hemodynamic parameters had no significant differences between the groups. Conclusion: The sufentanil and dexmedetomidine combination in spinal anesthesia caused the earlier onset and later regression of sensory and motor blocks, longer postoperative analgesia, and lower analgesic use without significant side effects or hemodynamic changes, which appears to be due to the combined effects of sufentanil and dexmedetomidine. Trial Registration Number: IRCT2017082833680N3.


Assuntos
Raquianestesia/normas , Dexmedetomidina/farmacologia , Sufentanil/farmacologia , Adjuvantes Anestésicos/farmacologia , Adjuvantes Anestésicos/uso terapêutico , Adulto , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Dexmedetomidina/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Irã (Geográfico) , Extremidade Inferior/fisiopatologia , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sufentanil/uso terapêutico
15.
Transplant Proc ; 53(6): 2060-2069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34238590

RESUMO

BACKGROUND: Dexmedetomidine is known to protect against ischemia-reperfusion (IR) in various organs; however, the mechanisms of dexmedetomidine in the liver remain unclear. We investigated whether dexmedetomidine preconditioning leads to hepatic protection and whether nitric oxide was associated with this protective mechanism by employing N-nitro-l-arginine methyl ester (l-NAME), a nitrous oxide synthase inhibitor. METHODS: Experiment 1 included 24 rats in 4 groups: sham, IR, 30 µg/kg of dexmedetomidine, and 50 µg/kg of dexmedetomidine. Experiment 2 included 36 rats in 6 groups: IR, 50 µg/kg of dexmedetomidine, 10 mg/kg of l-NAME, 10 mg/kg of l-NAME + 50 µg/kg of dexmedetomidine, 30 of mg/kg l-NAME, and 30 mg/kg of l-NAME + 50 µg/kg of dexmedetomidine. All drugs were administered intraperitoneally. The levels of serum transaminases, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase were measured 6 hours after hepatic surgery. RESULTS: Dexmedetomidine demonstrated a dose-dependent decrease in serum transaminase levels. The 50-µg/kg dexmedetomidine group showed a significant decrease in malondialdehyde levels (P = .002), increase in superoxide dismutase levels (P = .002), and a significantly lower level of phosphorylated tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase (P = .002, respectively) compared with the IR injury group. These protective effects of dexmedetomidine were partially reversed by pretreatment with l-NAME (P < .01 for 20 and 30 mg/kg of l-NAME). CONCLUSION: In hepatic IR injury, dexmedetomidine might protect the liver via antioxidative and anti-inflammatory responses, and nitric oxide production could play a role in these protective mechanisms.


Assuntos
Traumatismo por Reperfusão , Animais , Dexmedetomidina/farmacologia , Fígado , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico , Ratos , Traumatismo por Reperfusão/prevenção & controle
16.
Biochem Cell Biol ; 99(4): 457-464, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34296954

RESUMO

Numerous studies have indicated that microRNAs (miRNAs) play critical roles in the development and progression of cancer. However, how changes to the expression levels of miRNAs in response to dexmedetomidine affects the progression of lung cancer remains poorly understood. In this study, we treated the lung adenocarcinoma cell line-A549 with dexmedetomidine and then examined the changes to the expression levels of miRNAs. We found that one of the most significantly upregulated miRNAs was miR-493-5p, which has an important role in the growth and apoptosis of lung adenocarcinoma (LUAD) cells. In addition, bioinformatics searches and luciferase reporter assays revealed that miR-493-5p targets RASL11B, which has a high degree of similarity to RAS. Finally, database searches revealed that RASL11B is associated with survival of LUAD cells. In conclusion, dexmedetomidine causes changes to the expression levels of miRNAs in LUAD, including significant upregulation of miR-493-5p. MiR-493-5p targets RASL11B, thereby inhibiting cell growth and inducing apoptosis in LUAD.


Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Dexmedetomidina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Células Tumorais Cultivadas
17.
Croat Med J ; 62(3): 233-240, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34212560

RESUMO

AIM: To evaluate the consumption of remifentanil (as a primary end-point), analgesia, sedation, hemodynamics, respiratory effects, and surgeon and patient satisfaction (as a secondary end-point) with dexmedetomidine sedation compared with those of remifentanil sedation in patients undergoing vitreoretinal surgery. METHODS: Patients subjected to retinal ophthalmic surgical procedures were randomized to one of two intraoperative sedation groups: one group (n=21) received intranasal dexmedetomidine plus intravenous remifentanil (DEX-REMI group), and the other group (n=19) received intravenous remifentanil only (REM group). The treatment was placebo-controlled. The sedation level was controlled according to the bispectral index, with target values between 80%-90%. Patient levels of comfort, sedation, and pain were documented. The number of intraoperative complications and the level of satisfaction were assessed. Remifentanil consumption and hemodynamic parameters were also included in the statistical analysis. RESULTS: The level of remifentanil consumption was significantly lower in the DEX-REMI group, but combination sedation improved the surgeon's, anesthesiologist's, and patients' satisfaction scores. Importantly, the number of complications was zero in the DEX-REMI group, while eight cases of complications were noted in the REM group. The DEX-REMI group showed lower mean minimal arterial pressure, but it was still in the normotensive range. CONCLUSIONS: For patients undergoing ophthalmic procedures, sedation with a combination of intranasal dexmedetomidine and an intravenous infusion of remifentanil provides lower remifentanil consumption, better satisfaction scores, and a lower complication rate than sedation with a remifentanil infusion alone.


Assuntos
Dexmedetomidina , Dexmedetomidina/farmacologia , Hemodinâmica , Humanos , Hipnóticos e Sedativos/farmacologia , Piperidinas/farmacologia , Remifentanil/farmacologia
18.
J Nanosci Nanotechnol ; 21(12): 6205-6211, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229822

RESUMO

The aim of this study was to explore the neurocognitive effects of dexmedetomidine-loaded gold nanoparticles (AuNPs-dexmedetomidine) on anesthetized rats. Sixty Sprague Dawley rats (age, 2-3 weeks; weight, 250-280 g) were randomly divided into three groups (n = 20): the control group and two groups that received intraperitoneal injection of AuNPs-dexmedetomidine at 50 and 100 µg/kg each. Western blotting and RT-PCR were used to determine the protein and mRNA expression of GSK-3ß, respectively. Compared with that in the control group, GSK-3ß expression in AuNP-dexmedetomidine groups increased (P < 0.05). The protein expression of GSK-3ß was higher and mRNA expression was significantly lower in the 100 µg/kg AuNP-dexmedetomidine group (P < 0.05). AuNPs-dexmedetomidine reduced the neurocognitive effect on anesthetized rats through the regulation of the GSK-3ß signaling pathway.


Assuntos
Dexmedetomidina , Nanopartículas Metálicas , Animais , Dexmedetomidina/farmacologia , Glicogênio Sintase Quinase 3 beta , Ouro , Ratos , Ratos Sprague-Dawley
19.
Sci Rep ; 11(1): 13110, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162952

RESUMO

Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.


Assuntos
Anestésicos Combinados/farmacologia , Encéfalo/efeitos dos fármacos , Dexmedetomidina/farmacologia , Isoflurano/farmacologia , Ketamina/farmacologia , Xilazina/farmacologia , Animais , Encéfalo/diagnóstico por imagem , Dexmedetomidina/administração & dosagem , Neuroimagem Funcional , Infusões Intravenosas , Isoflurano/administração & dosagem , Ketamina/administração & dosagem , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/efeitos dos fármacos , Xilazina/administração & dosagem
20.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34109426

RESUMO

As is well known, dexmedetomidine (DEX) serves a neuroprotective role in cerebral ischemia­reperfusion (CIR) injury, and microRNA (miR)­199a has been re­ported to be associated with IR injury. However, the association between DEX and miR­199a in CIR injury remains unknown. Thus, the aim of the present study was to verify whether the neuroprotective effect of DEX on cerebral ischemia­reperfusion rats is associated with miR­199a. A rat model of CIR was established, and the modified neurological severity score (mNSS) was evaluated. The effect of DEX on the patholog­ical structure of the cerebral cortex in CIR rats was observed by hematoxylin and eosin and Nissl staining. Reverse transcription­quantitative PCR was used to analyze the expression levels of miR­199a in brain tissue following intracerebroventricular injection of miR­199a antagomir. The co­expression of NeuN and microtubule­associated proteins 1A/1B light chain 3B in the cerebral cortex was analyzed by immunofluorescence staining. Western blotting and immunohistochemistry were performed to analyze the expression of autophagy­associated proteins in the brain tissue. DEX inhibited the expression of miR­199a, decreased the mNSS and improved pathological damage to the cerebral cortex. DEX also inhibited autophagy and expression levels of associated proteins and decreased nerve cell injury. In conclusion, DEX inhibited expression of miR­199a and improved neurocyte injury induced by CIR.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Dexmedetomidina/farmacologia , MicroRNAs/genética , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Animais , Antígenos Nucleares/metabolismo , Proteína Beclina-1/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Dexmedetomidina/administração & dosagem , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Injeções , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Proteínas de Ligação a RNA/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
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