DNA methylation is involved in the microRNA-886-3p gene expression and plays a potential role in hematopoietic stem and progenitor cell mobilization through affecting SDF-1

The role of the sympathetic nervous system (SNS) in hematopoietic stem and progenitor cell (HSPC) mobilization has been largely investigated. However, there is a critical need for the identification of the underlying contributing factors to improve HSPC yield for transplantation. It has been demonstrated that miR-886-3p targets stromal-derived factor-1 (SDF-1), the central mediator of mobilization, and therefore may play a part in this process. Besides, miR-886-3p expression can be epigenetically regulated through DNA methylation modifications inits gene promoter. Here, to assess the contribution of miR-886-3p and other epigenetic factors in HSPC mobilization, human bone marrow-derived mesenchymal stem cells (MSCs) were treated with the ?-adrenergic agonist of isoprenaline. The expression of miR-886-3p and SDF-1and the gene promoter methylation status of this miRNA were then respectively evaluated through the appropriate PCR techniques. As expected, despite a transient initial increase in SDF-1mRNA level, its expression reduced, and miR-886-3plevel remarkably increased 48 h following treatment. The gene promoter methylation pattern of miR-886-3p also changed from a full methylated state to a partially methylated one. Together, our findings suggest that miR-886-3p can be epigenetically regulated and through suppressing the expression of SDF-1 play an active role in the SNS-mediated HSPC mobilization.

Anestesia intravenosa contínua com cetamina racêmica ou dextrocetamina e detomidina em cadelas / [Continuous intravenous anesthesia with racemic ketamine or dextroketamine and detomidine in female dogs]

Objetivou-se com este estudo comparar a associação de detomidina e cetamina ou dextrocetamina, por via intravenosa contínua, em oito cadelas submetidas a dois protocolos: GCD - indução anestésica com 5mg/kg e infusão intravenosa contínua de 20mg/kg/h de cetamina; e GDD - indução com 3,5mg/kg e infusão de 14mg/kg/h de dextrocetamina. Associou-se detomidina, 30µg/kg/h, em ambos os grupos. Registraram-se frequência cardíaca (FC), pressão arterial (PA), frequência respiratória (f), temperatura (TC), miorrelaxamento, analgesia, hemogasometria e eletrocardiograma, antes e 15 minutos após a MPA (Mbasal e Mmpa); após o início da infusão (Mic); a cada 10 minutos até 90 minutos (M10, M20, M30, M40, M50, M60, M70, M80 e M90); e 30 minutos após o fim da infusão (M120). Foi observada bradicardia em Mmpa no GCD e de Mmpa a M10 no GDD. Ocorreu hipotensão em Mmpa e hipertensão a partir de Mic. A f diminuiu de M10 a M30. Foram observados: onda T de alta amplitude, bloqueios atrioventriculares e parada sinusal. Ocorreu acidose respiratória. O período de recuperação foi de 219,6±72,3 minutos no GCD e de 234,1±96,8 minutos no GDD. A cetamina e a dextrocetamina, associadas à detomidina por infusão contínua, causam efeitos cardiorrespiratórios e anestésicos similares.(AU)

The combination of detomidine and ketamine or dextrocetamine for continuous intravenous infusion was compared in eight female dogs submitted to two protocols: GCD - 5mg/kg of anesthetic induction and continuous intravenous infusion of ketamine 20mg/kg/h; and GDD - induction with 3.5mg/kg and infusion of 14mg/kg/h of dextrocetamine. Detomidine, 30µg/kg/h was associated in both groups. Heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature (CT), myorelaxation, analgesia, blood gas analysis and electrocardiogram were recorded before and 15 minutes after MPA (Mbasal and Mmpa); after the start of infusion (Mic); every 10 minutes to 90 minutes (M10, M20, M30, M40, M50, M60, M70, M80 and M90); and 30 minutes after the end of infusion (M120). Bradycardia was observed in Mmpa in GCD and from Mmpa to M10 in GDD. There was hypotension in Mmpa and hypertension from Mic. The RR decreased from M10 to M30. High amplitude T wave, atrioventricular blocks and sinus arrest were observed. Respiratory acidosis occurred. The recovery period was 219.6±72.3 minutes in GCD and 234.1±96.8 minutes in GDD. Ketamine and S+ ketamine associated with detomidine for continuous infusion cause cardiorespiratory and similar anesthetic effects.(AU)

Membrane Interactivity of Anesthetic Adjuvant Dexmedetomidine Discriminable from Clonidine and Enantiomeric Levomedetomidine

Aims: Dexmedetomidine, which has been increasingly used as an anesthetic adjuvant, is more lipophilic and more active than another α2-adrenergic agonist clonidine and enantiomeric levomedetomidine. Lipophilicity and stereostructure affect the clinical effects of α2-adrenergic agonists. We aimed to compare the membrane interactivity of dexmedetomidine with clonidine and levomedetomidine from a point of view different from the mode of action on α2-adrenergicreceptors.Methodology:Unilamellar vesicles were prepared with phospholipids and cholesterol to mimic the lipid compositions of peripheral nerve cell, central nerve cell and cardiomyocyte membranes, and lipid rafts. They were subjected to the reactions with dexmedetomidine, clonidine and levomedetomidine at 10-200 μM, followed by measuring fluorescence polarization to determine the membrane interactivity to change membrane fluidity and specify the membrane regionfor the stereostructure-specific interaction.Original ResearchArticle Results:Dexmedetomidine and clonidine acted on lipid bilayers to increase the membrane fluidity with potencies varying by a compositional difference of membrane lipids. Dexmedetomidine showed greater interactivity with neuro-mimetic and cardiomyocyte-mimetic membranes than clonidine, being consistent with their comparative lipophilicity and activity. The effects of α2-adrenergic agonists on lipid raft model membranes were much weaker than those on other membranes, indicating that lipid rafts are not mechanistically relevant to them. Higher interactive dexmedetomidine was discriminated from lower interactive levomedetomidine in the presence of chiral cholesterol in membranes. An interactivity difference between two enantiomers was largest in the superficial region of lipid bilayers and the rank order of their membrane-interacting potency was reversed by replacing cholesterol with epicholesterol, suggesting that cholesterol’s 3β-hydroxyl groups positioned close to the membrane surface are responsible for the enantioselective interaction.Conclusion:Dexmedetomidine structure-specifically interacts with biomimetic membranes depending on their lipid compositions more potently than clonidine and levomedetomidine. Such membrane interactivity associated with higher lipophilicity and stereostructure characterizes dexmedetomidine in addition to higher affinity for α2-adrenergic receptors

A step-up ractopamine feeding program for finishing pigs / Niveles incrementales de ractopamina para cerdos en ceba / Plano de níveis aumentados de ractopamina para suínos em terminação

Abstract Background: Ractopamine (RAC) supplementation in the feed has been evaluated as a strategy to increase productive efficiency in finishing pigs. Objective: To evaluate the effects of different RAC dietary levels on performance, carcass traits, efficiency of lysine (ELU) and energy (EEU) utilization, and economic viability in finishing pig. Methods: A total of 40 barrows (74.75 ± 5.22 kg) were fed four RAC levels (0, 5, 10 and 5-10 mg/kg step-up program) from 0-14, 15-31 and 0-31 days. Performance, carcass characteristics, ELU, EEU, cost per unit of weight gain (CWG), payment and profit parameters were measured. The animals were distributed in a completely randomized design in four treatments, with ten replicates per treatment. The experimental unit was each animal. Results: Pigs fed RAC diets showed increased body weights at 14 and 31 days, average daily gain (ADG) at 0-14 and 0-31 days, ELU at 0-14 days, and hot carcass weight as compared with those fed the control diet. The step-up program as compared to the 10 mg/kg RAC concentration resulted in increased body weight, feed/gain ratio (FGR), ADG, ELU, EEU and CWG at 0-14 days. Payment by weight and bonus payment were better for treatments with RAC as compared to control. Conclusions: Pigs fed RAC improved performance, carcass weight, ELU, EEU and economic viability. The results were better for the step-up program compared with the intermittent use of 10 mg/kg RAC.

Resumen Antecedentes: La suplementación de cerdos con ractopamina (RAC) es una estrategia para aumentar la eficiencia productiva en ceba. Objetivo: Evaluar el efecto de diferentes planes de suplementación con RAC en dietas de cerdos en ceba sobre el rendimiento productivo, características de la canal, eficiencia de utilización de lisina (ELU) y energía (EEU), y viabilidad económica. Métodos: Un total de 40 machos castrados (74,75 ± 5,22 kg) fueron alimentados con cuatro niveles de RAC (0, 5, 10 y 5-10 mg/kg de plano escalonado) de 0-14, 15-31 y 0-31 días. Se evaluó el rendimiento, características de la canal, ELU, EEU, el costo por unidad de ganancia de peso (CWG), los tipos de pago y ganancias. Los animales se distribuyeron en un diseño completamente aleatorizado en cuatro tratamientos, con diez repeticiones por tratamiento. La unidad experimental fue cada animal. Resultados: Los animales suplementados con RAC tuvieron mayor peso corporal a los 14 y 31 días, ganancia de peso diaria (ADG) de 0-14 y 0-31 días, ELU de 0-14 días y peso de la canal caliente en comparación con el grupo control. En comparación con la concentración de 10 mg/kg de RAC, el plano escalonado resultó en un aumento de peso corporal, conversión alimenticia (FGR), ADG, ELU, EEU y CWG a los 0-14 días. El pago por peso y el pago por bonificación fueron mejores para los tratamientos con RAC en comparación con el control. Conclusiones: Los cerdos en ceba alimentados con RAC tienen mejor rendimiento, peso de la canal, ELU, EEU y viabilidad económica. Los resultados de los parámetros estudiados son mejores con el uso del plano escalonado en comparación con el uso continuo de 10 mg/kg de RAC.

Resumo Antecedentes: Suplementação de ractopamina (RAC) em dietas para suínos foi avaliada como uma estratégia para aumentar eficiência de produção de suínos em terminação. Objetivo: Avaliar os efeitos de diferentes planos de suplementação de RAC em dietas para suínos em terminação sobre o desempenho, características de carcaça, eficiência de utilização de lisina (ELU) e energia (EEU), e viabilidade econômica. Métodos: Um total de 40 machos castrados (74.75 ± 5.22 kg) foram alimentados com quatro níveis de RAC (0, 5, 10 e 5-10 mg/kg plano escalonado) em 0-14, 15-31 e 0-31 dias. Desempenho, características de carcaça, ELU, EEU, custo por unidade de ganho de peso (CWG), tipos de pagamento e lucro foram mensurados. Os animais foram distribuídos em um delineamento inteiramente casualizado em quatro tratamentos, dez repetições para cada tratamento. A unidade experimental foi cada animal. Resultados: Os animais alimentados com dietas contendo RAC mostraram aumento de peso corporal aos 14 e 31 dias, ganho de peso diário (ADG) de 0-14 e 0-31 dias, ELU de 0-14 dias e peso de carcaça quente comparado ao grupo controle. O plano escalonado comparado ao nível de 10 mg/kg de RAC mostrou maior peso corporal, conversão alimentar (FGR), ADG, ELU, EEU e CWG de 0-14 dias. Pagamento por peso e pagamento por bonificação foram melhor para tratamentos com RAC em comparação ao controle. Conclusões: Suínos alimentados com RAC mostram melhor desempenho, peso de carcaça, ELU, EEU e viabilidade econômica. Os resultados dos parâmetros estudados foram melhores com uso do plano escalonado quando comparado com uso constante de 10 mg/kg de RAC para suínos em terminação.

Metabolic and behavioral effects of ractopamine at continuous low levels in rats under stress

This study aimed at evaluating the effect of ractopamine (RAC) on metabolism, zootechnical performance, body composition, and behavior in Wistar rats submitted to acute and chronic restrain stress. The oral dose of 5 mg/kg of RAC was administered in periods of 0, 7, 14, 21, and 28 days. The elevated plus-maze test (EPMT) was used for behavioral assessment. Blood, carcass and viscera characteristics were evaluated. Insulin-dependent glucose transporters (GLUT-4) were semi-quantified by Western Blot in epididymal adipocytes. RAC periods associated with chronic stress increased the GLUT-4 protein expression in adipose tissue in a time-dependent manner (P=0.01), i.e., the longer the RAC addition period, the higher the GLUT-4 concentration in chronically stressed animals (0=1.42; 7=1.19; 14=2.03; 21=1.59; 28=2.35). The stress periods combined with RAC increased the time spent in the opened arms of the maze (Chronic stress: 0=10.6; 7=8.7; 14=5.9; 21=12.3; 28=4.0; Acute stress 0=3.1; 7= 4.7; 14=7.5; 21=0.0; 28=2.8) (P=0.04). Chronic (entries on the closed arms [ECA]=3.60) and acute (ECA=3.80) stress reduced locomotive activity in the maze (P=0.03). The results suggested that stress could negatively affect the possible benefits offered by the RAC, mainly impairing the adipose tissue metabolism and behavior in the animals.

Associação de ractopamina e vitaminas antioxidantes para suínos em terminação / Association of ractopamine and antioxidants vitamins for finishing pigs

Objetivou-se neste estudo avaliar a inclusão de ractopamina e sua associação com as vitaminas antioxidantes C e E em dietas de suínos em terminação durante 28 dias antes do abate sobre o desempenho, as características de carcaça e a qualidade da carne. Quarenta e oito suínos da linhagem Agroceres PIC (24 machos castrados e 24 fêmeas) foram distribuídos em delineamento experimental de blocos casualizados, em esquema fatorial 3x2, com três dietas: controle; controle + 10ppm de ractopamina; controle + complexo (0,05%) de ractopamina com vitaminas antioxidantes (10ppm de ractopamina + 200mg de vitamina E + 100mg de vitamina C kg-1 de ração) e dois gêneros (machos castrados e fêmeas). Foram avaliados o consumo de ração, o ganho de peso e a conversão alimentar dos animais. Os suínos foram abatidos com peso médio de 100,81±7,81kg. Após o abate, as características de carcaça foram avaliadas e foram coletadas amostras do músculo Longissimus dorsi para a análise da qualidade da carne. Verificou-se diferença (P<0,05) para a conversão alimentar, conformação da carcaça e pH final da carne dos animais que consumiram rações que continham ractopamina. A oxidação da carne foi menor para a dieta com o complexo (ractopamina + vitamina) em relação ao controle (0,10mg kg-1 vs 0,13mg kg-1 TBARS). O marmoreio da carne foi maior (P<0,05) na dieta controle + ractopamina em relação à dieta controle. Os valores de vitamina E no músculo foram mais elevados nos animais que ingeriram as vitaminas antioxidantes (0,23 vs 0,08mg kg-1 vit. E). Conclui-se que a inclusão de ractopamina, associada ou não às vitaminas antioxidantes, promoveu melhora na conversão alimentar e redução da oxidação lipídica da carne.

The objective of the study was to evaluate the inclusion of ractopamine and its association with the antioxidant vitamins C and E in finishing pig diets during 28 days prior to slaughter on the performance, carcass traits and meat quality. Forty-eight Agroceres PIC line swine (24 barrows and 24 females) distributed in a randomized blocks factorial design in 3x2 (3 diets: control; control+10ppm of ractopamine; control + complex (0.05%) ractopamine with antioxidant vitamins (10ppm of ractopamine + 200mg of vitamin E+100mg of vitamin C kg-1 of feed) and 2 sex (barrows and females). The feed intake, body weight gain and feed conversion were evaluated. When pigs reached 100.81±7.81kg body weight, they were slaughtered and carcasses were evaluated. Samples of Longissimus dorsi muscle were taken to evaluate the meat quality. Diets with ractopamine improved (P<0.05) feed conversion in pigs, carcass conformation and final pH. The lipid oxidation decreased with the diet (ractopamine+vitamin) in relation to the control diet (0.10mg kg-1 vs 0.13mg kg-1 TBARS). The marbling was higher (P<0.05) in the diet (control + ractopamine) in relation to the control diet. The levels of vitamin E in the muscle were higher in pigs that were fed with antioxidant vitamins (0.23 vs 0.08mg kg-1 vit. E). It was concluded that the inclusion of ractopamine associated or not to antioxidant vitamins improved feed conversion ratio of animals and reduces the lipid oxidation in meat.

Dexmedetomidine Ameliorates Histological and Neurological Outcomes after Transient Spinal Ischemia in Rats.

Aims: Dexmedetomidine, anα2adrenergicagonist, provides neuroprotection in various cerebral ischemia models and against anesthesia-related neurotoxicity. Dexmedetomidine also improves paraplegia induced by intrathecal morphine after short-term spinal ischemia. In this preliminary study, we investigated whether dexmedetomidine provides spinal protection against transient spinal ischemia in rats. Methodology: Adult male Sprague-Dawley rats were randomly divided into the following 3 groups: 1) intravenous infusion of 0.9% NaCl at a rate of 0.5 mL/h (control), 2) dexmedetomidine 1 μg/kg/h, and 3) intravenous infusion of 0.9% NaCl without spinal ischemia (sham). The rats received saline solution or dexmedetomidine 30 min before spinal cord ischemia and for 24 h. Spinal cord ischemia was induced by intra-aortic balloon occlusion combined with proximal arterial hypotension for 10 min. Ischemic injury was assessed by the neurological deficit score and by the number of viable motor nerve cells in the anterior spinal cord at 24 h of reperfusion. Results: The neurological deficit score was significantly lower in the dexmedetomidine group compared to the control group (p< 0.05). The number of viable motor nerve cells in the dexmedetomidine group was significantly greater than was that in the control group (p< 0.05), but was lower than was that in the sham group.Conclusion: Our findings suggest that continuous administration of dexmedetomidine ameliorates short-term neurological and histological outcomes induced by transient spinal cord ischemia and reperfusion in rats; thus, dexmedetomidine appears to protect the spinal as well as the brain.

Effect of ractopamine on lipid metabolism in vivo - a systematic review

The aim of this article was to evaluate the in vivo mechanism of action through which ractopamine reduces the amount of adipose tissue in carcass of animals fed diets supplemented with this drug. Literature search was carried out, using the keywords Ractopamine, lipogenesis, lipolysis, fatty acid and adipose tissue. The scoring system was designed for the adequacy of the methodology. A total of eight papers were found - all published in the English language. The determination of lipolysis and lipogenesis was carried out using different methods - from the quantification of non-esterified fatty acids in the blood to molecular analyses of adipose tissue. The review analysis suggested that, at least in the pigs, the use of this drug reduced lipid deposition in the carcass due to a greater inhibition of lipogenesis than an increase in lipolysis.

Hormonal Sensitivity of Adenylyl Cyclase in the Myocardium, Brain and Testes of 18-month-old Non-Diabetic and Diabetic Rats.

The alterations and abnormalities in hormone-sensitive adenylyl cyclase (AC) system occur at early stages of the type 2 diabetes mellitus (T2DM) and at later stages of the disease they are, according to our view, one of the factors causing T2DM complications. To study the changes in AC system likely to be involved in the development of these complications one needs a very long model of T2DM. Purpose: The aim of this work was the study of AC system in the myocardium, brain and testes of three-, eight- and 18-month-old male rats with experimental T2DM compared with control animals of the same age.

Ractopamine as a metabolic modifier feed additive for finishing pigs: a review

The β-adrenergic agonist ractopamine is increasingly used in the swine industry due to higher consumer demand for leaner pork products. Redirecting nutrients to favor leanness rather than fat deposition, ractopamine improves growth and carcass traits of finishing pigs. However, the impact of this agonist on pork quality is not clearly defined. Understanding the biological effects of dietary ractopamine dose, treatment period, lysine levels, and the lysine to metabolizable energy ratio will help pork producers achieve improvements in animal performance, carcass leanness, and economic efficiency in swine production systems.

Assessment of Bronchodilator Responsiveness Following Methacholine-Induced Bronchoconstriction in Children With Asthma

PURPOSE: The aim of this study was to investigate bronchodilator responsiveness (BDR) following methacholine-induced bronchoconstriction and to determine differences in BDR according to clinical parameters in children with asthma. METHODS: The methacholine challenge test was performed in 145 children with mild to moderate asthma, and the provocative concentration causing a 20% decline in FEV1 (PC20) was determined. Immediately after the challenge test, patients were asked to inhale short-acting beta2-agonists (SABAs) to achieve BDR, which was assessed as the change in FEV1% predictedx100/post-methacholine FEV1% predicted. For each subject, the asthma medication, blood eosinophil count, serum total IgE, serum eosinophil cationic protein level, and skin prick test result were assessed. RESULTS: The FEV1 (mean+/-SD) values of the 145 patients were 90.5+/-10.9% predicted, 64.2+/-11.5% predicted, and 86.2+/-11.2% predicted before and after methacholine inhalation, and following the administration of a SABA, respectively. The BDR did not differ significantly according to asthma medication, age, or gender. However, BDR in the atopy group (37.4+/-17.7%) was significantly higher than that in the non-atopy group (30.5+/-10.7%; P=0.037). Patients with blood eosinophilia (38.6+/-18.1%) displayed increased BDR compared with patients without eosinophilia (32.0+/-13.8%; P=0.037). CONCLUSIONS: In children with mild to moderate asthma, the responsiveness to short-acting bronchodilators after methacholine-induced bronchoconstriction was not related to asthma medication, but was higher in children with atopy and/or peripheral blood eosinophilia.

Alimentação de suínos em terminação com dietas contendo ractopamina e extratos cítricos: desempenho e características de carcaça / Pigs fed containing ractopamine and citrus extracts: performance and carcass characteristics

Um experimento avaliou a adição de ractopamina e extratos cítricos a dietas de suínos em terminação. Foram utilizados 108 suínos (54 machos e 54 fêmeas) em um delineamento de blocos completos ao acaso, sendo o sexo o fator de bloqueamento e nove os tratamentos: T1. controle (C) (0ppm de ractopamina e 0ppm de extratos cítricos), T2. C+10RAC (ractopamina, em ppm), T3. C+20RAC, T4. C+250EC (extratos cítricos, em ppm), T5. C+500EC, T6. C+250EC+10RAC, T7. C+250EC+20RAC, T8. C+500EC+10RAC e T9. C+500EC+20RAC. O peso vivo final (109,9±3,6kg), consumo de ração (2,6±0,2kgd-1), ganho de peso (1,0±0,1kgd-1), conversão alimentar (2,7±0,2), comprimento de carcaça (97,0±2,7cm), profundidade de músculo (56,1±5,6mm) e pH (5,9±0,3) não foram influenciados pelos tratamentos. Sobre o peso de carcaça, o efeito foi somente do tratamento com 20ppm de ractopamina em relação a 10ppm de ractopamina, sendo 5,7 por cento superior. A espessura de toucinho do grupo controle foi 35 por cento superior aos níveis de ractopamina, e a interação foi 500ppm de extratos cítricos e 10ppm de ractopamina. A carne magra do controle foi 5,3 por cento inferior em relação aos níveis de ractopamina. A alimentação de suínos em terminação com dietas contendo ractopamina, extratos cítricos e suas interações não altera o desempenho, mas influencia algumas características de carcaça.

This study was carried out to evaluate the effect of the addition of the citrus extracts and ractopamine in finishing pig diets. A Hundred eight pigs were used (54 males and 54 females) in a completely randomized design, blocked by sex and distributed in nine treatments: T1. control (C) (0ppm of the ractopamine e 0ppm of the citrus extracts), T2. C+10RAC (ractopamine, ppm), T3. C+20RAC, T4. C+250EC (citrus extracts, ppm), T5. C+500EC, T6. C+250EC+10RAC, T7. C+250EC+20RAC, T8. C+500EC+10RAC and T9. C+500EC+20RAC. The final body weight (109.9±3.60kg), feed intake (2.6±0.24kg d-1), body weight gain (1.01±0.09kg d-1), feed conversion ratio (2.7±0.25), carcass length (97±2.71cm), depth muscle (56.1±5.63mm), and pH (5.9±0.33) were not affected by treatments. There was a significant effect for the treatment with 20ppm of ractopamine, which was 5.7 higher, in relation to the treatment with 10ppm of ractopamine. The backfat thickness of control group was 35 percent higher than the ractopamine levels and the interaction was of 10ppm of ractopamine and 500ppm of citrus extracts. The lean meat in the control group was on average, 5.3 percent lower in relation to the ractopamine levels. Feeding of finishing pigs with diets containing ractopamine, citrus extracts and their interactions didn't affect performance, however affected some carcass characteristics.

Efeitos hemodinâmicos da combinação de dexmedetomidina-fentanil versus midazolam-fentanil em crianças submetidas à cirurgia cardíaca com circulação extracorpórea / Efectos hemodinámicos de la combinación de dexmedetomidina-fentanil versus midazolam-fentanil en ninõs sometidos a la cirugía cardíaca con circulación extracorpórea / Hemodynamic effects of the combination of dexmedetomidine-fentanyl versus midazolam-fentanyl in children undergoing cardiac surgery with cardiopulmonary bypass

JUSTIFICATIVA E OBJETIVOS: Avaliar a eficácia da infusão combinada de dexmedetomidina e fentanil na resposta hemodinâmica durante cirurgia cardíaca com circulação extracorpórea (CEC) em crianças. MÉTODO: Trinta e duas crianças com idade entre 1 mês e 10 anos, agendadas para cirurgia cardíaca com circulação extracorpórea, foram distribuídas de modo aleatório em dois grupos: o Grupo MDZ recebeu midazolam 0,2 mg.kg-1.h-1, enquanto o Grupo DEX recebeu dexmedetomidina 1 µg.kg-1.h-1 durante uma hora e, em seguida, o ritmo de infusão foi reduzido à metade em ambos os grupos. Ambos os grupos receberam fentanil 10 µg.kg-1, midazolam 0,2 mg.h-1 e vecurônio 0,2 mg.kg-1 para indução da anestesia. As mesmas doses de fentanil com vecurônio da indução foram infundidas durante a primeira hora após a indução e, em seguida, reduzidas à metade. As infusões foram iniciadas imediatamente após a indução e mantidas até o final da cirurgia. O isoflurano foi administrado por curto tempo para controle da resposta hiperdinâmica à incisão e esternotomia. RESULTADOS: Em ambos os grupos, a pressão arterial sistólica e a frequência cardíaca reduziram de modo significativo após uma hora de infusão anestésica, porém o aumento da pressão arterial sistólica e diastólica e da frequência cardíaca à incisão da pele foram significantemente menores no Grupo DEX. Um número significativamente menor de pacientes demandaram suplementação com isoflurano no Grupo DEX. Após a CEC, os pacientes de ambos os grupos tiveram respostas hemodinâmicas similares. CONCLUSÕES: A infusão sem bolus de dexmedetomidina parece ser um adjuvante efetivo do fentanil na promoção de sedação e controle das respostas hemodinâmicas durante cirurgia para cardiopatias congênitas em crianças.

BACKGROUND AND OBJECTIVES: To evaluate the efficacy of the combined infusion of dexmedetomidine and fentanyl on the hemodynamic response during cardiac surgery with cardiopulmonary bypass (CPB) in children. METHODS: Thirty-two children, ages 1 month to 10 years, scheduled for cardiac surgery with cardiopulmonary bypass were randomly divided in two groups: the MDZ Group received midazolam 0.2 mg.kg-1.h-1, while the DEX group received dexmedetomidine 1 µg.kg-1.h-1 during one hour followed be a reduction by half in the rate of infusion in both groups. Both groups received fentanyl 10 µg.kg-1, midazolam 0.2 mg.h-1, and vecuronium 0.2 mg.kg-1 for anesthesia induction. The same doses of fentanyl and vecuronium used during induction were infused during the first hour after induction, followed by a reduction to half. Infusions were initiated immediately after induction and maintained until the end of the surgery. Isoflurane was administered for a short time to control the hyperdynamic response to incision and sternotomy. RESULTS: In both groups, systolic blood pressure and heart rate reduced significantly after one hour of anesthetic infusion, but the increase in systolic and diastolic pressure and heart rate to skin incision were significantly lower in the DEX Group. A significantly lower number of patients demanded supplementation with isoflurane in the DEX Group. After CPB, patients in both groups had similar hemodynamic responses. CONCLUSIONS: Infusion of dexmedetomidine without bolus seems to be an effective adjuvant to fentanyl on the promotion of sedation and control of hemodynamic responses during surgery for congenital cardiopathies in children.

JUSTIFICATIVA Y OBJETIVOS: Evaluar la eficacia de la infusión combinada de dexmedetomidina y fentanil en la respuesta hedominámica durante la cirugía cardíaca con circulación extracorpórea (CEC) en niños. MÉTODO: Treinta y dos niños, con edad entre 1 mes y 10 años, citados para cirugía cardíaca con circulación extracorpórea, que fueron distribuidos aleatoriamente en dos grupos: el Grupo MDZ recibió midazolam 0,2 mg.kg-1.h-1, mientras que el Grupo DEX recibió dexmedetomidina 1 µg.kg-1.h-1 durante una hora y enseguida el ritmo de infusión se redujo a la mitad en los dos grupos. Los dos grupos recibieron fentanil 10 µg. kg-1, midazolam 0,2 mg.h-1 y vecuronio 0,2 mg.kg-1 para la inducción de la anestesia. Las mismas dosis de fentanil con vecuronio de la inducción fueron infundidas durante la primera hora después de la inducción y enseguida reducidas a la mitad. Las infusiones fueron iniciadas inmediatamente después de la inducción y mantenidas hasta el final de la cirugía. El isoflurano se administró por un corto tiempo para el control de la respuesta hiperdinámica a la incisión y esternotomía. RESULTADOS: En los dos grupos, la presión arterial sistólica y la frecuencia cardíaca se redujeron ostensiblemente después de una hora de infusión anestésica, pero el aumento de la presión arterial sistólica y diastólica y el de la frecuencia cardíaca al momento de la incisión de la piel, fueron significantemente menores en el Grupo DEX. Un número significativamente menor de pacientes exigió un suplemento con isoflurano en el Grupo DEX. Después de la CEC, los pacientes de los dos grupos tuvieron respuestas hedominámicas similares. CONCLUSIONES: La infusión sin bolo de dexmedetomidina parece ser un adyuvante efectivo del fentanil en la promoción de la sedación y el control de las respuestas hemodinámicas durante la cirugía para las cardiopatías congénitas en niños.

Effects in Lumen Width of Nasolacrimal Drainage System After Adrenergic Drug Irrigation

PURPOSE: The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries, and the blood vessels of the cavernous body are innnervated by the autonomic nervous system. The purpose of this study was to determine the effect of an adrenergic agonist on the lumen width of the nasolacrimal drainage system. METHODS: Dacryocystography was performed on 35 patients with only epiphora and not nasolacrimal duct obstruction. The anteroposterior (AP) diameters and the oblque diameters of the nasolacrimal ducts were measured. Next, 18 patients were infused with 0.5 ml Alphagan-P(R) (alpha-2 adrenergic receptor agonist), 17 patients were infused with 0.5 ml DL methylephedrine hydrochloride (alpha-1 and alpha-2 adrenergic receptor agonist), and dacryocystography was performed again to determine the change in the lumen width of the nasolacrimal drainage system. RESULTS: The alpha-adrenergics caused a significant increase in the lumen width of the nasolacrimal drainage system, and the changes were more pronounced in the nasolacrimal duct than in the lacrimal sac. Although the nasolacrimal duct widening was more notable in the Alphagan-P(R) infusion group than the DL methylephedrine hydrochloride infusion group, there was no significant statistical difference. Patients' subjective symptoms improved in both groups. CONCLUSIONS: The alpha-adrenergics constrict the blood vessels of the cavernous body, leading to the increase in the lumen width of the nasolacrimal drainage system. This effect was more significant in the Alphagan-P(R) infusion group. In conclusion, infusion of alpha-adrenergics in patients with functional nasolacrimal duct obstruction can be considered as an alternative to surgical management.

Effects of α-methylnorepinephrine on cardiac function and myocardium at early stage of postresuscitation in rabbits / 中华急诊医学杂志

Objective To observe the effects of selective α2-adrenergic receptor agonist alpha-Methylnore-pinephrine(α-MNE) as a vasopressin agent on hemodynamics, troponin T(cTnT) and myocardium in the rabbit cardiopulmonary resuscitation. Method Eighteen health rabbits, weighing 2.5 - 3.5 kg, both male and female,were provided by Lanzhou institute of veterinary medicine. After setting up rabbit model of cardiopulmonary resuscitation, 18 rabbits were randomly divided into three groups. The rabbits in group A as a operation-control group were processed with anesthesia, endotracheal intubation, and surgery without ventricular fibrillation induced. The rabbits in group B as a epinephrine group were administered with 30 ug/kg epinephrineduring CPR. The rabbits in group C as a MNE group were administered with 100 ug/kg α-MNE during CPR. The left ventrictdar end-diastolic pressure(LVEDP), left ventricular pressure rise and fall rate(± dp/dt) and serum concentrations of BNP were measured. Statistic package of SPSS 10.0 was used for the data analysis and significant differences between means were evaluated by ANOVA analysis. Results Compared with group A, LVEDP of other two groups gradually increased respectively(P < 0. 01), and peak ± dp/dt decreased in other two groups(P<0.01). Increase in LVEDP in group C was less than that in group B(P<0.05), whereas peak ± dp/dt in group C were higher than that in group B(P<0.05), at the same stage. Compared with group A, the cTnT of the remaining two groups increased(P<0.01, respectively),and reached peak at 30 minutes. In group C, the elevation of cTnT was less than that in group B(P<0.05) during the same period. In group B and C, myocardial injury was seen under a light microscope, but the injury in group C was lighter than that in group B. Conclusion The methylnorepinephrine can lessen the myocardial dysfunction after CPR.

The Effect of Brimonidine on Transepithelial Resistance in a Human Retinal Pigment Epithelial Cell Line

PURPOSE: To investigate the effects of brimonidine, an alpha-2-adrenergic agonist, on barrier function in ARPE-19 cells by measuring transepithelial resistance (TER). METHODS: ARPE-19 cells were cultured into a confluent monolayer on a microporous filter. Brimonidine was added to the apical medium, and the barrier function of the cells was evaluated by measuring TER. A subset of cells was treated under hypoxic conditions, and the TER changes observed upon administration of brimonidine were compared to those observed in cells in normoxic conditions. RESULTS: The ARPE cell membrane reached a peak resistance of 29.1+/-7.97 Omega cm2 after four weeks of culture. The TER of the cells treated under normoxic conditions increased with brimonidine treatment; however, the TER of the cells treated under hypoxic conditions did not change following the administration of brimonidine. CONCLUSIONS: Barrier function in ARPE-19 cells increased with brimonidine treatment. Understanding the exact mechanism of this barrier function change requires further investigation.

Effects of α-methylnorepinephrine on cardiac function and myocardium at early stage of resuscitation in rabbits / 世界急诊医学杂志（英文）

BACKGROUND:Recent studies have shown that α2-adrenergic agonists can reduce postresuscitation myocardial injury. This study was undertaken to observe changes of hemodynamics, myocardial injury markers cTnT and cardiac morphology by establishing a cardiopulmonary resuscitation model with rabbits, and to detect whether α-methyl norepinephrine (α-MNE) can reduce the myocardial injury after CPR and improve cardiac function. METHODS:Eighteen health rabbits, weighing 2.5-3.5 kg, both male and female, were provided by the Lanzhou Institute of Veterinary Medicine. After setting up a rabbit model of cardiopulmonary resuscitation, 18 rabbits were randomly divided into three groups. The rabbits in group A as an operation-control group were subjected to anesthesia, endotracheal intubation, and surgery without induction of ventricular fibrillation. The rabbits in group B as an epinephrine group were administered with 30 g/kg epinephrineduring CPR. The rabbits in group C as a MNE group were administered with 100 g/kg a-MNE during CPR. The left ventricular end-diastolic pressure (LVEDP), left ventricular pressure rise and fall rate (±dp/dt) and serum concentrations of BNP were measured. Statistical package of SPSS 10.0 was used for data analysis and significant differences between means were evaluated by ANOVA. RESULTS:Compared to group A, the LVEDP of other two groups increased respectively (P<0.01 all), and peak±dp/dt decreased in the other two groups (P<0.01). The increase of LVEDP was lower in group C than in group B (P<0.05), whereas peak±dp/dt was higher in group C than in group B (P<0.05) at the same stage. Compared to group A, the cTnT of the remaining two groups increased, respectively (P<0.01), and peaked at 30 minutes. cTnT was less elevated in group C than in group B (P<0.05) during the same period. In groups B and C, myocardial injury was seen under a light microscope, but the injury in group C was lighter than that in group B. CONCLUSION:Methylnorepinephrine can lessen myocardial dysfunction after CPR.

The Influence of Influenza Virus A on Alveolar Fluid Clearance in Rat Lungs / 中国医科大学学报

Objective To investigate the influence of influenza virus A（H1N1,A/PR/8/34 strain）on alveolar fluid clearance（AFC）in vivo and the effects of β1-adrenergic agonist on AFC in rat lungs infected by H1N1.Methods Fortyfive rats were divided into control group（n =12）,H1N1 infection group（the rats were infected with influenza virus strain A/PR/8/34,n =18）,β1-adrenergic agonist groups（the rats were administrated with β1-adrenergic agonist after HIN1 infection,n =15）.AFC was estimated by the progressive increase in the albumin concentration over 30 minutes.The activity of cAMP and cGMP in the lung tissues of control,H1N1 infection and β1-adrenergic agonist groups was measured.Results The infection with H1N1 resulted in a decline in AFC 9.15±1.01% vs control group 17.25±1.01% and increased lung water content（W/D was 6.77±0.13 vs control group 4.99±0.02）.H1N1-mediated inhibition of AFC could be reversed to 14.41±1.41% by the administration of β1-adrenergic agonist denopamine.H1N1 infection increased cGMP levels 7.34±0.40 pmol·mg-1· mg-1 vs control group 5.10±1.88 pmol·mg-1·mg-1 and decreased cAMP levels 1.43±0.06 nmol·mg-1·mg-1 in lung tissues compared with control group.β1-agonist denopamine reversed the level of cAMP to 2.06±0.16 nmol·mg-1·mg-1 and cGMP to 6.16±1.36 pmol·mg-1·mg-1.Conclusion H1N1 infection decreased AFC and increased lung edema.β1-agonist denopamine could reverse AFC and the ratio of cAMP/cGMP in H1N1 infected lung tissues.β1-agonist might regulate AFC through the pathway of cAMP-PKA.

Infarto perioperatorio en cirugía no-cardíaca y dexmedetomidina / Perioperative myocardical infaction in non-cardiac surgery and dexmedetomidine

La patología cardiovascular es la primera causa de muerte en Chile y en el mundo. Desde el punto de vista quirúrgico, anestesiólogos y cirujanos enfrentan más frecuentemente pacientes mayores con patología cardiovascular. La incidencia de isquemia miocárdica en pacientes de alto riesgo, sometidos a cirugía no-cardíaca, es cercana al 40 por ciento durante el perioperatorio. La incidencia de infarto miocárdico y muerte en cirugía no-cardíaca, oscila entre 1 y 5 por ciento. Existe una estrecha relación entre los eventos isquémicos perioperatorios y el aumento de la morbimortalidad cardiovascular. Por este motivo, se han desarrollado medidas terapéuticas orientadas a disminuir la incidencia de isquemia perioperatoria y aminorar el daño asociado a ella. La adecuada identificación de pacientes de riesgo, la optimización del tratamiento médico de patologías asociadas y el uso de fármacos cardioprotectores durante el perioperatorio, han mostrado disminuir la incidencia de complicaciones cardíacas. Dexmedetomidina es un agonista beta2-adrenérgico de uso frecuente en anestesia. La evidencia sugiere que posee propiedades cardioprotectoras que podrían beneficiar a pacientes quirúrgicos de alto riesgo cardiovascular. La cardioprotección conferida por dexmedetomidina estaría mediada por la modulación del sistema nervioso autónomo. La disminución de la frecuencia cardíaca y de la presión arterial observada durante su uso, evitarían el desbalance entre aporte y demanda de oxígeno miocárdico y atenuarían el estrés sobre placas ateromatosas inestables. Hasta este momento se desconoce si dexmedetomidina produce precondicionamiento cardíaco y si activa vías transduccionales asociadas a cardioprotección. Frente a la actual realidad epidemiológica en Chile y el mundo, es importante estudiar y definir, cuales son los fármacos de uso frecuente en anestesia con capacidad cardloprotectora y los mecanismos Involucrados en esta protección. Sería Interesante lograr...

Cardiovascular disease is the leading cause of death In Chile and worldwide. Anesthesiologists and surgeons often face more elderly surgical patients with cardiovascular disease. The incidence of myocardial Ischemia in patents at high risk, undergoing non-cardiac surgery is about 40 percent during the perioperative period. The incidence of myocardial Infarction and death in non-cardiac surgery is between 1 and 5 percent. There is a close relationship between perioperative Ischemic events and increased cardiovascular morbidity and mortality Therefore, therapeutic approaches have been developed to reduce the Incidence of perioperative Ischemia and lessen the damage associated with it. The proper Identification of patients at risk, optimizing the medical treatment of associated diseases and the use of cardioprotective drugs during the perioperative period have shown to decrease the Incidence of cardiac complications. The beta2-adrenergic agonist dexmedetomidine is commonly used in anesthesia. The evidence suggests that possesses cardioprotective properties that could benefit surgical patients at high cardiovascular risk. The cardioprotection conferred by dexmedetomidine would be mediated by modulation of the autonomic nervous system. The decrease in heart rate and blood pressure observed during its use could avoid the Imbalance between supply and myocardial oxygen demand and lessen the stress on unstable athermanous plaques. So far it is unknown whether dexmedetomidine produces cardiac preconditioning by activating cardioprotective-signaling pathways. Faced with the current worldwide epidemiologic situation, It would be Important to study the cardioprotective capacity of drugs frequently used in anesthesia and the mechanisms Involved In that protection. It would be interesting to achieve that definition regarding the perioperative use of dexmedetomidine.

A Case of Amitraz Insecticide Intoxication after Ingestion of Large Amount

Amitraz is used as farm-animal insecticide. Its side effects in humans are related to its pharmacological activity on alpha 2-adrenergic receptors. The case describes a previously healthy 46-year-old woman who intentionally ingested approximately 250mL of liquid amitraz. She presented with vomiting, altered mental status, miosis, dry mouth, hypopnea, metabolic and respiratory acidosis, hypotension, hypothermia, polyuria, metabolic acidosis, elevated serum aminotransferase and abdominal distension. Supportive treatments including mechanical ventilation, hydration, dopamine infusion, bicarbonate infusion and gastric decompression resulted in improvement. By hospital day 3, she recovered with resolution of abdominal distension. It is paramount to recognize amitraz poisoning when apesticide-intoxicated patient presets with signs and symptoms consistent with organophosphate intoxicated patients but with greater alpha 2-adrenergic related symptoms such as decreased bowel motility and xerostomia.