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1.
Arq. bras. cardiol ; 117(6): 1134-1144, dez. 2021. graf
Article in Portuguese | LILACS | ID: biblio-1350046

ABSTRACT

Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.


Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.


Subject(s)
Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Reperfusion Injury , Myocardial Ischemia , Dexmedetomidine/pharmacology , Myocardial Infarction/prevention & control , Myocardial Infarction/drug therapy , Signal Transduction
3.
Acta Physiologica Sinica ; (6): 901-908, 2021.
Article in Chinese | WPRIM | ID: wpr-921294

ABSTRACT

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.


Subject(s)
Alanine Transaminase , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Dexmedetomidine/pharmacology , Galactosamine/toxicity , Interleukin-6/blood , Lipopolysaccharides/toxicity , Liver , Male , Mice , Mice, Inbred BALB C , Microtubule-Associated Proteins/metabolism , Tumor Necrosis Factor-alpha/blood , Up-Regulation
4.
Article in Chinese | WPRIM | ID: wpr-878726

ABSTRACT

Objective To explore the effect of dexmedetomidine(Dex)on sevoflurane-induced cognitive impairment in neonatal rats through Wnt signaling pathway. Methods Sixty 7-day-old SD rats were assigned into five groups:control group(without any intervention),Dex group(intraperitoneal injection of 25 μg/kg Dex),sevoflurane group(3% sevoflurane treatment for 4 hours),sevoflurane+Dex group(inhalation of 3% sevoflurane after injection of 25 μg/kg Dex for 4 hours),and sevoflurane+Dex+Wnt inhibitor group(Wnt inhibitor XAV393 and 25 μg/kg Dex were injected and 3% sevoflurane was inhaled for 4 hours).Three weeks later,Morris water maze was used to detect the cognitive function;TdT-mediated dUTP nick end labeling(TUNEL)staining was performed to detect the apoptosis of hippocampal neurons;neuronal nuclei (NeuN) staining was conducted to detect the survival of hippocampal neurons;Western blot was carried out to detect the expression of apoptosis-related proteins.The expression of the factors involved in Wnt/GSK-3β/β-catenin signaling pathway was detected by fluorescence quantitative polymerase chain reaction,and Western blot. Results Compared with the control group,there was no significant difference in the escape latency of Dex group(t=0.304,P=0.768);the escape latency in sevoflurane group(t=5.823,P=0.002),sevoflurane+Dex group(t=3.188,P=0.010),and sevoflurane+Dex+Wnt inhibitor group(t=5.784,P=0.002)was significantly prolonged.Compared with that in the sevoflurane group,the escape latency in sevoflurane+Dex group(t=3.646,P=0.005)was significantly shortened.Compared with that in sevoflurane+Dex group,the escape latency in sevoflurane+Dex+Wnt inhibitor group(t=3.296,P=0.008)was prolonged.Compared with that in the control group,the times of crossing platform in sevoflurane group(t=5.179, P=0.004),sevoflurane+Dex group(t=2.309,P=0.043),and sevoflurane+Dex+Wnt inhibitor group(t=3.871, P=0.003)decreased.Compared with that in sevoflurane group,the times of crossing platform in sevoflurane+Dex group(t=3.296,P=0.008)significantly increased.Compared with that in sevoflurane+Dex group,the times of crossing platform in sevoflurane+Dex+Wnt inhibitor group(t=2.361, P=0.041)reduced.Compared with the control group,there was no significant difference in the number of apoptotic cells in Dex group(t=1.920,P=0.127),and the number of apoptotic cells in sevoflurane group,sevoflurane+Dex group,and sevoflurane+Dex+Wnt inhibitor group increased by 16%(t=13.436,P=0.002),5%(t=7.752, P=0.001),and 11.5%(t=12.612,P=0.002),respectively.Compared with that in the sevoflurane group,the number of apoptotic cells in sevoflurane+Dex group and sevoflurane+Dex+Wnt inhibitor group decreased by 11%(t=8.521,P=0.002)and 5.5%(t=3.123,P=0.036),respectively.Compared with that in the sevoflurane+Dex group,the number of apoptotic cells in sevoflurane+Dex+Wnt inhibitor group increased by 6.5%(t=6.250,P=0.003).Compared with that in the control group,the number of positive cells in 0.15 mm


Subject(s)
Animals , Animals, Newborn , Cognitive Dysfunction/chemically induced , Dexmedetomidine/pharmacology , Glycogen Synthase Kinase 3 beta , Rats , Rats, Sprague-Dawley , Sevoflurane/toxicity , Wnt Signaling Pathway , beta Catenin/metabolism
5.
Acta Physiologica Sinica ; (6): 253-262, 2021.
Article in Chinese | WPRIM | ID: wpr-878254

ABSTRACT

The aim of this study was to investigate the effects of dexmedetomidine (Dex) on hepatic ischemia/reperfusion injury (HIRI) and the underlying mechanism. The in vitro HIRI was induced by culturing HL-7702 cells, a human hepatocyte cell line, under 24 h of hypoxia and 12 h of reoxygenation. Quantitative real time PCR (qRT-PCR) and Western blot were performed to detect the expression levels of long non-coding RNA MALAT1, microRNA-126-5p (miR-126-5p) and high mobility group box-1 (HMGB1). Bioinformatics prediction and double luciferase assay were used to verify the targeting relationship between miR-126-5p and MALAT1, HMGB1. Reactive oxygen species (ROS), malondialdehyde (MDA) and ATP levels in culture medium were detected by corresponding kits. The results showed that Dex significantly reduced the levels of ROS and MDA, but increased the level of ATP in HL-7702 cells with HIRI. HIRI up-regulated the expression levels of MALAT1 and HMGB1, and down-regulated the level of miR-126-5p. Dex reversed these effects of HIRI. Furthermore, Dex inhibited HIRI-induced cellular apoptosis, whereas MALAT1 reversed the effect of Dex. This inhibitory effect of Dex could be restored by up-regulation of miR-126-5p. The results suggest that Dex protects hepatocytes from HIRI via regulating MALAT1/miR-126-5p/HMGB1 axis.


Subject(s)
Dexmedetomidine/pharmacology , HMGB1 Protein/genetics , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Reperfusion Injury/genetics
6.
Rev. bras. anestesiol ; 70(2): 153-158, Mar.-Apr. 2020. tab
Article in English, Portuguese | LILACS | ID: biblio-1137159

ABSTRACT

Abstract Objective This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. Methods A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 µg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. Results The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p< 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p< 0.05). Conclusions Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction.


Resumo Objetivo Estudar o impacto em linfócitos causado pelo uso da dexmedetomidina associada à morfina para analgesia pós-toracotomia. Método Um total de 118 pacientes utilizando Analgesia Intravenosa Controlada pelo Paciente (AICP) pós-toracotomia em nosso hospital, de março de 2016 a julho de 2018, foram selecionados aleatoriamente e divididos em dois grupos: o Grupo Combinado [COM, 57 pacientes que receberam dexmedetomidina (1,0 µg.kg-1 de peso corpóreo) associada à morfina (0,48 mg.kg-1 de peso corpóreo)] e o Grupo Morfina [MOR, 61 pacientes, que receberam somente morfina (0,48 mg.kg-)]. Os valores dos subconjuntos de linfócitos (CD3+, CD4+ e CD8+) e das células NK no sangue periférico desses dois grupos foram medidos por citometria de fluxo FACSCalibur em diferentes momentos do estudo [antes da indução anestésica (T0), imediatamente após extubação traqueal (T1), 12 horas após a cirurgia (T2), 24 horas após a cirurgia (T3), 48 horas após a cirurgia (T4), 72 horas após a cirurgia (T5) e 7 dias após a cirurgia (T6)]. As doses de morfina do momento T3 ao T5 e as reações adversas entre os dois grupos também foram registradas e comparadas. Resultados O nível de CD3+ e a razão CD4+/CD8+ de T2 a T5, e o nível de CD4+ e as células NK de T3 a T5 do Grupo COM foram significantemente maiores (p< 0,05) quando comparados ao Grupo MOR. A dose de morfina no pós-operatório e a incidência de prurido, náusea e vômito no pós-operatório foram significantemente menores no grupo MOR (p< 0,05). Conclusões Dexmedetomidina combinada com morfina para AICP no período pós-toracotomia pode melhorar a função dos linfócitos, reduzir o consumo de morfina e diminuir reações adversas durante a analgesia.


Subject(s)
Humans , Male , Female , Adult , Pain, Postoperative/drug therapy , Thoracotomy , Killer Cells, Natural/drug effects , Analgesia, Patient-Controlled , Lymphocyte Subsets/drug effects , Analgesics, Non-Narcotic/pharmacology , Dexmedetomidine/pharmacology , Analgesics, Opioid/pharmacology , Morphine/pharmacology , Analgesics, Non-Narcotic/therapeutic use , Dexmedetomidine/therapeutic use , Analgesics, Opioid/therapeutic use , Middle Aged , Morphine/therapeutic use
7.
Acta cir. bras ; 34(11): e201901105, Nov. 2019. graf
Article in English | LILACS | ID: biblio-1054679

ABSTRACT

Abstract 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.


Subject(s)
Animals , Male , Spine/drug effects , Dexmedetomidine/pharmacology , Diabetic Neuropathies/drug therapy , Receptors, Purinergic P2X4/analysis , Adrenergic alpha-2 Receptor Agonists/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/analysis , Sural Nerve/drug effects , Time Factors , Random Allocation , Blotting, Western , Pain Threshold , Microscopy, Electron, Transmission , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Neuropathies/pathology , Disease Models, Animal , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Neural Conduction/drug effects
8.
Rev. bras. anestesiol ; 69(2): 160-167, Mar.-Apr. 2019. graf
Article in English | LILACS | ID: biblio-1003397

ABSTRACT

Abstract Background and objectives: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 8): control group, hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine (DEX1) group, and 10 ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20 min. 30 min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. Results: Compare with hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25 ± 0.24 vs. 4.12 ± 0.42%, p < 0.05), histological score (1.06 ± 0.12 vs. 1.68 ± 0.15, p < 0.05) and protein (1.92 ± 0.38 vs. 3.95 ± 0.42 mg.mL-1, p < 0.05) and WBC (0.42 ± 0.11 vs. 0.92 ± 0.13 × 109/L, p < 0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35 ± 0.68 vs. 4.73 ± 0.44 U.mg-1 protein, p < 0.05) and decreased malondialdehyde (2.18 ± 0.19 vs. 3.28 ± 0.27 nmoL.mg-1 protein, p < 0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55 ± 0.04 vs. 0.34 ± 0.05, p < 0.05) and decreased the level of Bax (0.46 ± 0.03 vs. 0.68 ± 0.04, p < 0.05), caspase-3 (0.49 ± 0.03 vs. 0.69 ± 0.04, p < 0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p > 0.05). Conclusion: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.


Resumo Justificativa e objetivos: Dexmedetomidina demonstrou efeitos protetores contra a lesão pulmonar in vitro. Neste estudo, investigamos se o pré-condicionamento com dexmedetomidina protege contra a lesão pulmonar em ratos com choque hemorrágico. Métodos: Ratos machos, Sprague-Dawley, foram aleatoriamente divididos em quatro grupos (n = 8): grupo controle, grupo com choque hemorrágico, grupo com 5 µg.kg-1 de dexmedetomidina (DEX1) e grupo com 10 µg.kg-1 de dexmedetomidina (DEX2). Solução salina ou dexmedetomidina foi administrada durante 20 minutos. Trinta minutos após a injeção, a hemorragia foi iniciada nos grupos choque hemorrágico, DEX1 e DEX2. Quatro horas após a ressuscitação, a proteína e o conteúdo celular no lavado broncoalveolar e a histopatologia pulmonar foram medidos. Malondialdeído, superóxido dismutase, Bcl-2, Bax e caspase-3 também foram testados no tecido pulmonar. Resultados: Na comparação com o grupo choque hemorrágico, o pré-tratamento com 5 ug.kg-1 de dexmedetomidina reduziu a apoptose (2,25 ± 0,24 vs. 4,12 ± 0,42%, p < 0,05), escore histológico (1,06 ± 0,12 vs. 1,68 ± 0,15, p < 0,05) e proteína (1,92 ± 0,38 vs. 3,95 ± 0,42 mg.mL-1, p < 0,05) e leucócitos (0,42 ± 0,11 vs. 0,92 ± 0,13 × 109/L, p < 0,05) no lavado broncoalveolar; o que está correlacionado com o aumento da atividade da superóxido dismutase (8,35 ± 0,68 vs. 4,73 ± 0,44 U.mg-1 de proteína, p < 0,05) e diminuição do malondialdeído (2,18 ± 0,19 vs. 3,28 ± 0,27 nmoL.mg-1 de proteína, p < 0,05). O pré-condicionamento com dexmedetomidina também aumentou o nível de Bcl-2 (0,55 ± 0,04 vs. 0,34 ± 0,05, p < 0,05) e diminuiu o nível de Bax (0,46 ± 0,03 vs. 0,68 ± 0,04, p < 0,05), caspase-3 (0,49 ± 0,03 vs. 0,69 ± 0,04, p < 0,05). No entanto, não houve diferença entre os grupos DEX1 e DEX2 para essas proteínas (p > 0,05). Conclusão: O pré-condicionamento com dexmedetomidina tem um efeito protetor contra a lesão pulmonar causada por choque hemorrágico em ratos. Os potenciais mecanismos envolvidos são a inibição da morte celular e a melhora da antioxidação. Porém, não mostrou um efeito dose-dependente.


Subject(s)
Animals , Male , Rats , Shock, Hemorrhagic/drug therapy , Protective Agents/administration & dosage , Dexmedetomidine/administration & dosage , Lung Injury/prevention & control , Rats , Shock, Hemorrhagic/complications , Bronchoalveolar Lavage Fluid , Rats, Sprague-Dawley , Apoptosis/drug effects , Protective Agents/pharmacology , Dexmedetomidine/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Lung Injury/etiology
9.
Acta cir. bras ; 33(4): 314-323, Apr. 2018. tab
Article in English | LILACS | ID: biblio-886285

ABSTRACT

Abstract Purpose: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. Methods: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 μg/kg), Group D2 (5.5 μg/kg), and Group D3 (8.25 μg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. Results: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). Conclusion: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.


Subject(s)
Animals , Male , Rats , Dexmedetomidine/pharmacology , Hemodynamics/drug effects , Hypnotics and Sedatives/pharmacology , Reference Values , Time Factors , Random Allocation , Reproducibility of Results , Dexmedetomidine/blood , Heart Function Tests , Heart Ventricles/drug effects , Hemodynamics/physiology , Hypnotics and Sedatives/blood
10.
Acta cir. bras ; 33(1): 22-30, Jan. 2018. tab
Article in English | LILACS | ID: biblio-886251

ABSTRACT

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.


Subject(s)
Animals , Male , Rats , Myocardial Reperfusion Injury/prevention & control , Dexmedetomidine/pharmacology , Adrenergic alpha-2 Receptor Agonists/pharmacology , Reference Values , Thromboxane A2/blood , Platelet Activating Factor/analysis , Myocardial Reperfusion Injury/physiopathology , Random Allocation , Reproducibility of Results , Treatment Outcome , Endothelin-1/blood , Disease Models, Animal , No-Reflow Phenomenon/physiopathology , Heart Rate/drug effects , Hemodynamics
11.
Acta cir. bras ; 33(1): 1-13, Jan. 2018. tab, graf
Article in English | LILACS | ID: biblio-886254

ABSTRACT

Abstract Purpose: To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. Methods: An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. Results: The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Conclusion: Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.


Subject(s)
Animals , Male , Reperfusion Injury/prevention & control , Dexmedetomidine/pharmacology , Adrenergic alpha-2 Receptor Agonists/pharmacology , Ischemia/prevention & control , Lung/blood supply , Reference Values , Superoxide Dismutase/analysis , Time Factors , Reperfusion Injury/pathology , Blotting, Western , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , CCAAT-Enhancer-Binding Proteins/analysis , Disease Models, Animal , Real-Time Polymerase Chain Reaction , Heat-Shock Proteins/analysis , Lung/pathology , Malondialdehyde/analysis
12.
Rev. bras. anestesiol ; 67(6): 600-606, Nov.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-897789

ABSTRACT

Abstract Background and objectives Dexmedetomidine (DEX) has demonstrated the preconditioning effect and shown protective effects against organize injury. In this study, using A549 (human alveolar epithelial cell) cell lines, we investigated whether DEX preconditioning protected against acute lung injury (ALI) in vitro. Methods A549 were randomly divided into four groups (n = 5): control group, DEX group, lipopolysaccharides (LPS) group, and D-LPS (DEX + LPS) group. Phosphate buffer saline (PBS) or DEX were administered. After 2 h preconditioning, the medium was refreshed and the cells were challenged with LPS for 24 h on the LPS and D-LPS group. Then the malondialdehyde (MDA), superoxide dismutase (SOD), Bcl-2, Bax, caspase-3 and the cytochrome c in the A549 were tested. The apoptosis was also evaluated in the cells. Results Compare with LPS group, DEX preconditioning reduced the apoptosis (26.43% ± 1.05% vs. 33.58% ± 1.16%, p < 0.05) in the A549, which is correlated with decreased MDA (12.84 ± 1.05 vs. 19.16 ± 1.89 nmoL.mg-1 protein, p < 0.05) and increased SOD activity (30.28 ± 2.38 vs. 20.86 ± 2.19 U.mg-1 protein, p < 0.05). DEX preconditioning also increased the Bcl-2 level (0.53 ± 0.03 vs. 0.32 ± 0.04, p < 0.05) and decreased the level of Bax (0.49 ± 0.04 vs. 0.65 ± 0.04, p < 0.05), caspase-3 (0.54 ± 0.04 vs. 0.76 ± 0.04, p < 0.05) and cytochrome c. Conclusion DEX preconditioning has a protective effect against ALI in vitro. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation.


Resumo Justificativa e objetivos Dexmedetomidina (DEX) demonstrou ter efeito pré-condicionante e também efeitos protetores contra lesão organizada. Neste estudo, com células A549 (células epiteliais alveolares humanas), investigamos se o pré-condicionamento com DEX proporcionaria proteção contra lesão pulmonar aguda (LPA) in vitro. Métodos Células A549 foram aleatoriamente distribuídas em quatro grupos (n = 5): controle, DEX, lipopolissacarídeos (LPS) e D-LPS (DEX + LPS). Administramos solução de PBS (tampão fosfato-alcalino) ou DEX. Após 2 h de pré-condicionamento, o meio foi renovado e as células desafiadas com LPS por 24 h nos grupos LPS e D-LPS. Em seguida, malondialdeído (MDA), superóxido dismutase (SOD), Bcl-2, Bax, caspase-3 e em A549 foram testados. Apoptose também foi avaliada nas células. Resultados Em comparação com o grupo LPS, o pré-condicionamento com DEX reduziu a apoptose (26,43% ± 1,05% vs. 33,58% ± 1,16%, p < 0,05) em células A549, o que está correlacionado com a diminuição de MDA (12,84 ± 1,05 vs. 19,16 ± 1,89 nmol.mg-1 de proteína, p < 0,05) e aumento da atividade de SOD (30,28 ± 2,38 vs. 20,86 ± 2,19 U.mg-1 de proteína, p < 0,05). O pré-condicionamento com DEX também aumentou o nível de Bcl-2 (0,53 ± 0,03 vs. 0,32 ± 0,04, p < 0,05) e diminuiu o nível de Bax (0,49 ± 0,04 vs. 0,65 ± 0,04, p < 0,05), caspase-3 (0,54 ± 0,04 vs. 0,76 ± 0,04, p < 0,05) e citocromo c. Conclusão O pré-condicionamento com DEX tem efeito protetor contra LPA in vitro. Os potenciais mecanismos envolvidos são inibição da morte celular e melhoria da antioxidação.


Subject(s)
Humans , Lipopolysaccharides/adverse effects , Dexmedetomidine/pharmacology , Alveolar Epithelial Cells/drug effects , Hypnotics and Sedatives/pharmacology , Random Allocation , Cells, Cultured , Lipopolysaccharides/antagonists & inhibitors
13.
Acta cir. bras ; 32(6): 459-466, June 2017. tab, graf
Article in English | LILACS | ID: biblio-886207

ABSTRACT

Abstract Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy. Results: Compared to group C, Glu contents in group D, and I/R significantly increased. Compared to group I/R, Glu contents in group D significantly decreased. Compared to group C, GABA contents in group D, and I/R significantly increased, and those in group D significantly increased, as compared to group I/R. The cerebral ultrastructure was normal in group C. Vacuolar degeneration in the plastiosome and nervous processes, was more critical than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary, these changes in group D significantly improved. Conclusion: Dexmedetomidine is capable of decreasing glutamergic content, and increasing GABAergic content, in order to decrease the injury of the cerebral ultrastructure, following cerebral ischemia-reperfusion injury.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/metabolism , Cerebral Cortex/chemistry , Brain Ischemia/drug therapy , Neuroprotective Agents/pharmacology , Dexmedetomidine/pharmacology , Glutamine/metabolism , Cerebral Cortex/ultrastructure , Brain Ischemia/metabolism , Rats, Wistar , gamma-Aminobutyric Acid/drug effects , gamma-Aminobutyric Acid/metabolism , Amino Acids/drug effects , Amino Acids/metabolism
14.
Rev. bras. anestesiol ; 67(2): 193-198, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-843384

ABSTRACT

Abstract Background and objectives: Sevoflurane is often used in pediatric anesthesia and is associated with high incidence of psychomotor agitation. In such cases, dexmedetomidine (DEX) has been used, but its benefit and implications remain uncertain. We assessed the effects of DEX on agitation in children undergoing general anesthesia with sevoflurane. Method: Meta-analysis of randomized clinical and double-blind studies, with children undergoing elective procedures under general anesthesia with sevoflurane, using DEX or placebo. We sought articles in English in PubMed database using the following terms: Dexmedetomidine, sevoflurane (Methyl Ethers/sevoflurante), and agitation (Psychomotor Agitation). Duplicate articles with children who received premedication and used active control were excluded. It was adopted random effects model with DerSimonian-Laird testing and odds ratio (OR) calculation for dichotomous variables, and standardized mean difference for continuous variables, with their respective 95% confidence interval (CI). Results: Of 146 studies identified, 10 were selected totaling 558 patients (282 in DEX group and 276 controls). The use of DEX was considered a protective factor for psychomotor agitation (OR = 0.17; 95% CI 0.13-0.23; p < 0.0001) and nausea and vomiting in PACU (OR = 0.49; 95% CI 0.35-0.68; p < 0.0001). Wake-up time and PACU discharge time were higher in the dexmedetomidine group. There was no difference between groups for extubation time and duration of anesthesia. Conclusion: Dexmedetomidine reduces psychomotor agitation during wake-up time of children undergoing general anesthesia with sevoflurane.


Resumo Justificativa e objetivos: Sevoflurano é frequentemente usado em anestesia pediátrica e está associado à alta incidência de agitação psicomotora ao despertar. Nesses casos a dexmedetomidina (dex) tem sido usada, porém permanecem incertos seus benefícios e suas implicações. Foram avaliados os efeitos da dex sobre a agitação no despertar de crianças submetidas à anestesia geral com sevoflurano. Método: Metanálise de ensaios clínicos randomizados e duplamente encobertos, com crianças submetidas a procedimentos eletivos sob anestesia geral com sevoflurano, que usaram dex ou placebo. Buscaram-se artigos em língua inglesa na base de dados Pubmed com termos como Dexmedetomidine, sevoflurane (Methyl Ethers/sevoflurane) e agitation (Psychomotor Agitation). Artigos duplicados, com crianças que receberam medicação pré-anestésica e que usaram controle ativo foram excluídos. Adotou-se modelo de efeitos aleatórios com testes de DerSimonian-Laird e cálculo de odds ratio (OR) para variáveis dicotômicas e diferença de média padronizada para variáveis contínuas, com seus respectivos intervalos de confiança de 95% (IC). Resultados: Dos 146 estudos identificados, 10 foram selecionados, com 558 pacientes (282 no grupo dex e 276 controles). O uso da dex foi considerado fator de proteção para agitação psicomotora (OR = 0,17; 95% IC 0,13-0,23; p < 0,0001) e para náuseas e vômitos na SRPA (OR = 0,49; 95% IC 0,35-0,68; p < 0,0001). Tempo para despertar e para alta da SRPA foram maiores no grupo dexmedetomidina. Não houve diferença entre os grupos para tempo de extubação e duração da anestesia. Conclusão: A dexmedetomidina reduz a agitação psicomotora no despertar de crianças submetidas à anestesia geral com sevoflurano.


Subject(s)
Humans , Child , Psychomotor Agitation/prevention & control , Dexmedetomidine/administration & dosage , Methyl Ethers/adverse effects , Psychomotor Agitation/etiology , Randomized Controlled Trials as Topic , Anesthetics, Inhalation/administration & dosage , Anesthetics, Inhalation/adverse effects , Postoperative Nausea and Vomiting/prevention & control , Dexmedetomidine/pharmacology , Sevoflurane , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Anesthesia, General/adverse effects , Anesthesia, General/methods , Methyl Ethers/administration & dosage
15.
Rev. bras. anestesiol ; 67(2): 139-146, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-843368

ABSTRACT

Abstract Purpose: Ischemia-reperfusion injury is one of the consequences of tourniquet application for extremity surgery. The aim of the study was to establish the effect of dexmedetomidine on the acute lung injury following lower extremity experimental ischemia-reperfusion model in rats. Methods: Twenty-eight Wistar-Albino breed Rats were recruited after Ethics Committee approval and allocated into 4 groups, each with 7 subjects. Group 1 (SHAM) received only anesthesia. Group 2 (IR) had experienced 3 h of ischemia and 3 h of reperfusion using left lower extremity tourniquet after anesthesia application. Groups 3 (D-50) and 4 (D-100) had undergone the same procedures as in the Group 2, except for receiving 50 and 100 mg·kg-1, respectively, dexmedetomidine intraperitoneally 1 h before the tourniquet release. Blood samples were obtained for the analysis of tumor necrosing factor-α and interleukin-6. Pulmonary tissue samples were obtained for histological analysis. Results: No significant difference regarding blood tumor necrosing factor-α and interleukin-6 values was found among the groups, whereas pulmonary tissue injury scores revealed significant difference. Histological scores obtained from the Group 2 were significantly higher from those in the Groups 1, 3 and 4 with p-values 0.001 for each comparison. Moreover, Group 1 scores were found to be significantly lower than those in the Groups 3 and 4 with p-values 0.001 and 0.011, respectively. No significant difference was observed between the Groups 3 and 4. Conclusion: Dexmedetomidine is effective in reduction of the experimental ischemia-reperfusion induced pulmonary tissue injury in rats, formed by extremity tourniquet application.


Resumo Objetivo: A lesão de isquemia-reperfusão é uma das consequências da aplicação do torniquete em cirurgias de extremidades. O objetivo do estudo foi determinar o efeito de dexmedetomidina em lesão pulmonar aguda após modelo experimental de isquemia-reperfusão em extremidade inferior de ratos. Métodos: Vinte e oito ratos albinos Wistar foram recrutados após aprovação do Comitê de Ética e alocados em quatro grupos, cada um com sete indivíduos. O Grupo 1 (Sham) recebeu apenas anestesia. O Grupo 2 (IR) foi submetido a 3 horas de isquemia e 3 horas de reperfusão com o uso de torniquete em extremidade inferior após a aplicação da anestesia. Os grupos 3 (D-50) e 4 (D-100) foram submetidos aos mesmos procedimentos do Grupo 2, exceto por receberem 50 e 100 mg.kg-1 de dexmedetomidina, respectivamente, por via intraperitoneal uma hora antes da liberação do torniquete. Amostras de sangue foram coletadas para análise de TNF-α e Interleucina-6 (IL-6). Amostras de tecido pulmonar foram coletadas para análise histológica. Resultados: Não houve diferença significativa quanto aos valores sanguíneos de TNF-α e IL-6 entre os grupos, enquanto os escores de lesão em tecidos pulmonares revelaram diferença significativa. Os escores histológicos obtidos no Grupo 2 foram significativamente maiores do que os dos grupos 1, 3 e 4, com valores-p de 0,001 para cada comparação. Além disso, os escores do Grupo 1 foram significativamente menores do que os dos grupos 3 e 4, com valores-p de 0,001 e 0,011, respectivamente. Não houve diferença significativa entre os grupos 3 e 4. Conclusão: Dexmedetomidina mostrou eficácia na redução de lesão em tecido pulmonar induzida por isquemia-reperfusão experimental em ratos, ocasionada por aplicação de torniquete em extremidade.


Subject(s)
Animals , Female , Rats , Reperfusion Injury/drug therapy , Dexmedetomidine/pharmacology , Acute Lung Injury/prevention & control , Adrenergic alpha-2 Receptor Agonists/pharmacology , Tourniquets/adverse effects , Reperfusion Injury/complications , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Rats, Wistar , Dexmedetomidine/administration & dosage , Lower Extremity/blood supply , Disease Models, Animal , Dose-Response Relationship, Drug , Adrenergic alpha-2 Receptor Agonists/administration & dosage
16.
Rev. bras. anestesiol ; 67(1): 57-66, Jan.-Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-843355

ABSTRACT

Abstract The present study was designed to test the hypothesis that high dose dexmedetomidine would increase the duration of antinociception to a thermal stimulus in a rat model of sciatic nerve blockade without causing nerve damage. The rats were anesthetized with isoflurane. After electromyography (EMG) recordings, right sciatic nerves were explored and perineural injections were delivered: Group D (n = 7), 40 µg µg kg-1 dexmedetomidine administration, Group II (n = 6), (0.2 mL) saline administration, Group III (n = 2), only surgically exploration of the right sciatic nevre. Time to paw withdrawal latency (PAW) to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline. The compound muscle action potential (CMAP) of right and left sciatic nerves were recorded 10 times per each nerve once more after perineural injections at 14 day. After EMG recordings, right and the part of left sciatic nerve were excised at a length of at minimum 15 mm for histopathological examination. Comparison of right/left CMAP amplitude ratios before and 14 days after the procedure showed a statistically significant difference (p = 0.000). There were no differences in perineural inflammation between the Group D, Group S, and Group E at 14 days.


Resumo O presente estudo foi desenvolvido para testar a hipótese de que dexmedetomidina em dose alta aumentaria a duração da antinocicepção a um estímulo térmico em modelo de rato de bloqueio do nervo ciático sem causar danos ao nervo. Os ratos foram anestesiados com isoflurano. Após os registros da eletromiografia (EMG), os nervos ciáticos direitos foram explorados e injeções perineurais foram administradas: Grupo D (n = 7) recebeu 40 µg/kg-1 de dexmedetomidina, Grupo II (n = 6) recebeu 0,2 mL de solução salina, Grupo III (n = 2) recebeu apenas exploração cirúrgica do nervo ciático direito. O tempo de latência de retirada da pata (LRP) a um estímulo térmico para ambas as patas e uma avaliação da função motora foram avaliados a cada 30 minutos após o bloqueio do nervo até o retorno à fase basal. O potencial de ação muscular composto (PAMC) dos nervos ciático direito e esquerdo foi registrado 10 vezes para cada nervo, mais uma vez, após as injeções perineurais no 14º dia. Após os registros da EMG, o nervo ciático direito e parte do esquerdo foram excisados com um comprimento de no mínimo 15 mm para exame histopatológico. A comparação das proporções da amplitude do PAMC direito/esquerdo antes e 14 dias após o procedimento mostrou uma diferença estatisticamente significativa (p = 0,000). Não houve diferenças em inflamação perineural entre os grupos D, S e E aos 14 dias.


Subject(s)
Animals , Male , Sciatic Nerve/drug effects , Analgesics, Non-Narcotic/pharmacology , Dexmedetomidine/pharmacology , Reaction Time , Analysis of Variance , Rats, Sprague-Dawley , Lower Extremity , Electric Stimulation , Electromyography , Nerve Block/methods , Neuritis/chemically induced
17.
Rev. bras. anestesiol ; 66(5): 456-464, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: lil-794812

ABSTRACT

Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.


Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.


Subject(s)
Animals , Male , Endothelium, Vascular/drug effects , Dexmedetomidine/pharmacology , gamma-Cyclodextrins/pharmacology , Hypnotics and Sedatives/pharmacology , Arteries/anatomy & histology , Arteries/drug effects , Rabbits , Endothelium, Vascular/anatomy & histology , Dexmedetomidine/administration & dosage , gamma-Cyclodextrins/administration & dosage , Ear, External/blood supply , Sugammadex , Hypnotics and Sedatives/administration & dosage , Injections, Intra-Arterial , Muscle, Smooth, Vascular/anatomy & histology , Muscle, Smooth, Vascular/drug effects
18.
Acta cir. bras ; 31(1): 8-14, Jan. 2016. graf
Article in English | LILACS | ID: lil-771854

ABSTRACT

PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.


Subject(s)
Animals , Male , Acute Kidney Injury/pathology , /pharmacology , Dexmedetomidine/pharmacology , Kidney/blood supply , Reperfusion Injury/complications , Actins/analysis , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Blood Urea Nitrogen , Blotting, Western , Creatinine/blood , HMGB1 Protein/analysis , Immunohistochemistry , Inflammation/etiology , Inflammation/metabolism , Intercellular Adhesion Molecule-1/analysis , Interleukin-1beta/analysis , Kidney/chemistry , Random Allocation , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , RNA , Reperfusion Injury/pathology , /analysis , Tumor Necrosis Factor-alpha/analysis
19.
Yonsei Medical Journal ; : 980-986, 2016.
Article in English | WPRIM | ID: wpr-63322

ABSTRACT

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.


Subject(s)
Adult , Aged , Airway Extubation , Anesthesia Recovery Period , Cough/drug therapy , Craniotomy/adverse effects , Dexmedetomidine/pharmacology , Double-Blind Method , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Piperidines/pharmacology , Prospective Studies , Reflex/drug effects , Respiratory System/blood supply , Young Adult
20.
Braz. j. med. biol. res ; 49(4): e4646, 2016. tab, graf
Article in English | LILACS | ID: lil-774524

ABSTRACT

Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared with a conventional total intravenous anesthesia (TIVA) group of 11 patients (4 females and 7 males). The endpoints used to assess inflammatory and biochemical responses to mini-CPB were plasma interleukin (IL)-1, IL-6, IL-10, interferon (INF)-γ, tumor necrosis factor (TNF)-α, C-reactive protein, creatine phosphokinase, creatine phosphokinase-MB, cardiac troponin I, cortisol, and glucose levels. These variables were determined before anesthesia, 90 min after beginning CPB, 5 h after beginning CPB, and 24 h after the end of surgery. Endpoints of oxidative stress, including thiobarbituric acid reactive species and delta-aminolevulinate dehydratase activity in erythrocytes were also determined. DEX+TIVA use was associated with a significant reduction in IL-1, IL-6, TNF-α, and INF-γ (P<0.0001) levels compared with TIVA (two-way ANOVA). In contrast, the surgery-induced increase in thiobarbituric acid reactive species was higher in the DEX+TIVA group than in the TIVA group (P<0.01; two-way ANOVA). Delta-aminolevulinate dehydratase activity was decreased after CPB (P<0.001), but there was no difference between the two groups. DEX as an adjuvant in anesthesia reduced circulating IL-1, IL-6, TNF-α, and INF-γ levels after mini-CPB. These findings indicate an interesting anti-inflammatory effect of DEX, which should be studied in different types of surgical interventions.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Anesthesia, Intravenous/methods , Coronary Artery Bypass/methods , Dexmedetomidine/pharmacology , Systemic Inflammatory Response Syndrome/prevention & control , Adrenergic alpha-2 Receptor Agonists/pharmacology , Analysis of Variance , Blood Glucose/analysis , C-Reactive Protein/analysis , Coronary Artery Bypass/adverse effects , Creatine Kinase/blood , Cytokines/blood , Hydrocortisone/blood , Prospective Studies , Reference Values , Systemic Inflammatory Response Syndrome/blood , Thiobarbituric Acid Reactive Substances/analysis , Time Factors , Troponin I/blood
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