Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial

Abstract Background Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. Methods Ninety patients ASA physical status I, II, and III (aged 18-60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2 mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. Results The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI) = 0.01 to 0.32, p= 0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p= 0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p< 0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p= 0.002, with an NNT of 2.8). Conclusion A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

Effectiveness of fixed doses of propranolol in the treatment of hemangiomas regardless of child's weight gain: a case report / Efetividade do tratamento de hemangiomas utilizando doses fixas de propranolol em comprimido independentemente do ganho de peso da criança: relato de caso

ABSTRACT Objective: To present the outcomes of fixed doses of propranolol tablets for the treatment of hemangiomas. Case description: Two illustrative cases of hemangioma in infant patients younger than six months old are described. Treatments were started in 2010 and 2011 and were monitored until August 2017. Patients were treated with fixed doses, initially calculated based on the upper limit of 3 mg/kg/day and administrated in two daily doses rounded down to the nearest multiple of five milligrams. Dosage was not adjusted to patients' weight gain. The tablets were crushed and then diluted in a maximum amount of 3 mL of water. This procedure was necessary because propranolol was not available in oral solution in 2009, when dosages available in the Brazilian market were 10, 40 and 80 mg. Both patients presented significative improvement in the first 60 days and were in complete remission by the end of the treatment. Comments: It is possible to treat patients with Propranolol 10 mg tablets, even though the dosage is not as precise as when calculated according to patients' weight. The maintenance of a fixed dose, ignoring the patient's progressive weight gains, helps avoiding the rebound effect and decreases complications.

RESUMO Objetivo: Apresentar a experiência com a utilização de propranolol em doses fixas, em forma de comprimido, para o tratamento de hemangiomas. Descrição do caso: Dois casos ilustrativos de portadores de hemangiomas com menos de seis meses de idade são descritos. O início de tratamento ocorreu nos anos de 2010 e 2011 com seguimento até agosto de 2017. Os pacientes foram tratados com doses fixas iniciais calculadas com limite máximo de 3 mg/kg/dia, divididas em duas doses diárias, sempre com quantidades múltiplas de 5 mg. Os comprimidos de 10 mg ou a sua metade eram macerados e diluídos em 3 mL de água. As doses não foram mais alteradas. Esse uso foi decorrente da ausência da forma líquida de propranolol em 2009, quando começamos a utilizar esse tratamento, sendo então apenas disponíveis comprimidos de 10, 40 e 80 mg. Os pacientes obtiveram melhora acentuada nos primeiros 60 dias e remissão completa posteriormente. Comentários: É possível o uso de comprimidos de 10 mg, apesar de resultar numa dose não exata, como a calculada por kg/peso. A manutenção da mesma dose, mesmo com aumento progressivo de peso, pode evitar o efeito rebote e diminuir o índice de complicações.

Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers

SUMMARY OBJECTIVES This study aimed at assessing the role of beta-blockers on preventing anthracycline-induced cardiotoxicity in adults. METHODS A systematic review was performed on electronic databases, including relevant studies that analysed beta-blockers as cardioprotective agents before the use of anthracyclines by adult oncologic patients. RESULTS After application of eligibility and selection criteria, eight articles were considered as high quality, complying with the proposed theme; all eight clinical trials, four of them placebo-controlled, with a total number of 655 patients included. From this sample, 281 (42.9%) used beta-blocker as intervention, and carvedilol was the most frequent (167 patients - 25.5%). Six studies were considered positive regarding the cardioprotection role played by beta-blockers, although only four demonstrated significant difference on left ventricle ejection fraction after chemotherapy on groups that used beta-blockers compared to control groups. Carvedilol and nebivolol, but not metoprolol, had positive results regarding cardioprotection. Other beta-blockers were not analysed in the selected studies. CONCLUSIONS Despite the potential cardioprotective effect of beta-blockers, as demonstrated in small and unicentric clinical trials, its routine use on prevention of anthracycline-associated cardiotoxicity demands greater scientific evidence.

RESUMO OBJETIVO Este estudo teve como objetivo analisar o papel dos betabloqueadores na prevenção da cardiotoxicidade induzida pelas antraciclinas em adultos. MÉTODOS Foi realizada uma revisão sistemática em bases de dados eletrônicos, incluindo os estudos relevantes que analisaram fármacos betabloqueadores como agentes cardioprotetores antes do início do uso de antraciclinas por pacientes oncológicos adultos. RESULTADOS Após aplicação dos critérios de elegibilidade e seleção, foram obtidos oito artigos considerados de boa qualidade, que se adequavam à temática proposta, sendo todos ensaios clínicos, quatro placebo-controlados, totalizando 655 pacientes incluídos. Destes, 281 (42,9%) fizeram uso de algum betabloqueador como intervenção, sendo o carvedilol o mais utilizado (167 pacientes - 25,5%). Seis estudos foram considerados positivos quanto à cardioproteção exercida pelos betabloqueadores, porém apenas quatro demonstraram diferença na fração de ejeção do ventrículo esquerdo após a quimioterapia nos grupos que usaram betabloqueadores em relação aos grupos controle. O carvedilol e o nebivolol, mas não o metoprolol, tiveram resultados positivos quanto à cardioproteção. Outros betabloqueadores não foram avaliados nos estudos incluídos. CONCLUSÕES Apesar de haver um potencial efeito cardioprotetor dos betabloqueadores, conforme demonstrado em ensaios clínicos pequenos e unicêntricos, sua utilização rotineira na prevenção da cardiotoxicidade associada às antraciclinas requer maiores comprovações científicas.

Investigation of the antioxidant effects of pheniramine maleate and nebivolol on testicular damage in rats with experimentally induced testis torsion

Abstract Purpose: To investigate the biochemical, histopathologic, and spermatogenetic changes in the detorsionated testicle after experimental torsion and to study the antioxidant effects of pheniramine maleate and nebivolol. Methods: Twenty-four Sprague-Dawley male rats were divided into 4 groups: Group 1: Sham; Group 2: Torsion/Detorsion (T/D); Group 3: T/D + Pheniramine maleate (PM); Group 4: T/D + Nebivolol (NB) group. Paroxanase (PON), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stres index (OSI) were measured, and spermatogenetic and histopathologic evaluation was performed in tissue and blood samples. Results: The evaluation of tissue TAS indicated no statistically significant difference in Group 3 compared to Group 2. A statistically significant increase was detected in Group 4 compared to Group 2. Serum PON levels revealed a statistically significant increase in Groups 3 and 4 compared to Groups 1 and 2. The Johnsen testicular biopsy score decreased in Groups 3 and 4, but the decrease was not statistically significant. Conclusions: Pheniramine maleate and nebivolol have antioxidant effects against ischemia-reperfusion damage. They also support tissue recovery, which is more significantly observed by nebivolol.

Participation of hepatic α/β-adrenoceptors and AT1 receptors in glucose release and portal hypertensive response induced by adrenaline or angiotensin II

It has been previously demonstrated that the hemodynamic effect induced by angiotensin II (AII) in the liver was completely abolished by losartan while glucose release was partially affected by losartan. Angiotensin II type 1 (AT1) and adrenergic (∝1- and β-) receptors (AR) belong to the G-proteins superfamily, which signaling promote glycogen breakdown and glucose release. Interactive relationship between AR and AT1-R was shown after blockade of these receptors with specific antagonists. The isolated perfused rat liver was used to study hemodynamic and metabolic responses induced by AII and adrenaline (Adr) in the presence of AT1 (losartan) and ∝1-AR and β-AR antagonists (prazosin and propranolol). All antagonists diminished the hemodynamic response induced by Adr. Losartan abolished hemodynamic response induced by AII, and AR antagonists had no effect when used alone. When combined, the antagonists caused a decrease in the hemodynamic response. The metabolic response induced by Adr was mainly mediated by ∝1-AR. A significant decrease in the hemodynamic response induced by Adr caused by losartan confirmed the participation of AT1-R. The metabolic response induced by AII was impaired by propranolol, indicating the participation of β-AR. When both ARs were blocked, the hemodynamic and metabolic responses were impaired in a cumulative effect. These results suggested that both ARs might be responsible for AII effects. This possible cross-talk between β-AR and AT1-R signaling in the hepatocytes has yet to be investigated and should be considered in the design of specific drugs.

Efecto inotrópico y cronotrópico del propranolol sobre aurículas extraídas de ratas con insulina-resistencia inducida por fructosa / Inotropic and chronotropic effects of propranolol in isolated atrium of rats with fructose-induced insulin-resistance

La insulina-resistencia (IR) es una deficiencia metabólica asociada princi palmente con diabetes tipo 2 y comúnmente relacionada a la etiopatogenia de enfermedades cardiovasculares, siendo el factor determinante del síndrome metabólico. La investigación pretende conocer los efectos cronotrópico e inotrópico del propranolol sobre aurículas de ratas IR. Para ello, 16 ejemplares Sprague-Dawley, fueron divididos en Grupo control, alimentado ad libitum con alimento para perros Perrarina® y Grupo experimental, alimentado con Perrarina®-manteca vegetal, y suministro de agua con fructosa (20%)-sacarosa (20%) durante ocho meses. Al finalizar este periodo, se verificó la insulina-resistencia y las aurículas extraídas se mantuvieron en solución Krebs (37ºC, pH 7,4; 95% O2 - 5% CO2), en baño de órganos aislados marca Letica®, conectado a un polígrafo Grass®, registrándose la frecuencia de los latidos y evaluando las diferencias a través de la prueba t de Student (grado de significancia p<0,05). Se establecieron curvas dosis-respuesta acumulativas con isoproterenol y previa incubación de 15 minutos con propranolol (1x10 -6 M), registrándose un efecto cronotrópico negativo en el grupo control mas no así en las ratas IR, estableciéndose diferencias significativas entre el porcentaje de incremento de los latidos/seg en ambos grupos (Control 58,81±4,08; IR 68,84±4,16; p<0,001). La máxima fuerza de contracción auricular alcanzada por el grupo IR con propranolol (278,47±11,22), generó diferencias significativas (p<0,001), en comparación con el grupo control (42,60±3,13), evidenciándose que el propranolol no generó bloqueo sobre los receptores beta-adrenérgicos auriculares de las ratas insulina-resistentes.

Insulin resistance (IR) is a metabolic deficiency associated with type 2 diabe tes and commonly related to the pathogenesis of cardiovascular diseases, being the determining factor of the metabolic syndrome. This research aims to understand the chronotropic and inotropic effects of Propranolol in isolated atrium of rats with fructose-induced insulin-resistance. For this reason, 16 male Sprague-Dawley rats were assigned to two groups and given ad libitum access to one of the following diets: Perrarina® dog chow or Perrarina® dog chow supplemen ted with vegetable shortening and with fructose (20%) and sucrose (20%) added to the water supply. Both groups were maintained on their respective dietary regimens for eight months. At the end of this period insulin resistance was verified by routine blood test. The rat hearts were rapidly removed, and the atria were dissected and kept in Krebs solutions (37ºC, pH 7.4; 95% O2 - 5% CO2) in an isolated organ bath Letica®, connected to a polygraph Grass®, registering atria frequency. The Student ́s t-test was used to evaluate statistical differences between the two groups (p<0.05). Cumulative dose-response curves with isoproterenol were established in basal condition, and after fifteen minutes of pre-incubation with propranolol (1x10 -6 M). A significant positive chronotropic effect was observed in IR rats (8.84±4.16 vs 58.81±4.08 beats/sec of control; p<0.001). The maximum force of atrial contraction after pre-incubation with propranolol was significantly higher in the IR group (278.47±11.22 atrial contraction percentage; p<0.001). These findings suggest that a blunted response of atrial β-adrenoceptor to propranolol exists in rats with fructose-induced insulin-resistance.

Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Marfan Syndrome Patients after Aortic Root Replacement

PURPOSE: In this study, we evaluated the long term beneficial effect of Renin-Angiotensin-Aldosterone System (RAAS) blockade therapy in treatment of Marfan aortopathy. MATERIALS AND METHODS: We reviewed Marfan syndrome (MFS) patients who underwent aortic root replacement (ARR) between January 1996 and January 2011. All patients were prescribed beta-blockers indefinitely. We compared major aortic events including mortality, aortic dissection, and reoperation in patients without RAAS blockade (group 1, n=27) to those with (group 2, n=63). The aortic growth rate was calculated by dividing the diameter change on CT scans taken immediately post-operatively and the latest scan available. RESULTS: There were no differences in clinical parameters except for age which was higher in patients with RAAS blockade. In group 1, 2 (7%) deaths, 5 (19%) aortic dissections, and 7 (26%) reoperations occurred. In group 2, 3 (5%) deaths, 2 (3%) aortic dissections, and 3 (5%) reoperations occurred. A Kaplan-Meier plot demonstrated improved survival free from major aortic events in group 2. On multivariate Cox, RAAS blockade was an independent negative predictor of major aortic events (hazard ratio 0.38, 95% confidence interval 0.30-0.43, p=0.002). Mean diameter change in descending thoracic and supra-renal abdominal aorta was significantly higher in patients without RAAS blockade (p<0.05). CONCLUSION: In MFS patients who underwent ARR, the addition of RAAS blockade to beta-blocker was associated with reduction of aortic dilatation and clinical events.

Efeitos combinados do ácido zoledrônico e do propranolol sobre a densidade óssea e marcadores bioquímicos de remodelação óssea em ratas osteopênicas submetidas à ovariectomia / Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats

Objetivos: Este estudo foi desenvolvido para investigar a eficácia e a segurança do ácidozoledrônico (ZOL) e do propranolol (PRO) como monoterapia e terapia combinada em ummodelo de rato com osteoporose pós-menopáusica. Métodos: Ratas Wistar fêmeas foram ovariectomizadas (OVX) ou submetidas à cirurgia simulada (placebo) aos três meses de idade. Doze semanas depois da cirurgia, as ratas foram divididas em seis grupos: (1) placebo + veículo; (2) OVX + veículo; (3) OVX + ZOL (100 µg/kg, dose única intravenosa); (4) OVX + ZOL (50 µg/kg, dose única intravenosa); (5) OVX + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana); (6) OVX + ZOL (50 µg/kg, dose única intravenosa) + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana) durante 12 semanas. Depois do tratamento, testou-se a densidade óssea, a porosidade e a microarquitetura tra-becular dos fêmures. Também foram avaliados marcadores bioquímicos séricos e urinários. Resultados: A terapia combinada com ZOL mais PRO foi mais eficaz em corrigir a diminuição do cálcio sérico e o aumento do nível sérico de fosfatase alcalina e fosfatase ácida resistenteao tartarato do que a monoterapia com ZOL ou PRO. Além disso, a terapia combinada comZOL mais PRO foi mais eficaz em corrigir o aumento dos níveis urinários de cálcio, fósforo ecreatinina do que a monoterapia com ZOL ou PRO. A terapia combinada com ZOL mais PRO também preservou a microarquitetura trabecular e a porosidade do osso cortical. Conclusão: Os resultados sugerem que a terapia combinada com ZOL mais PRO pode ser aabordagem mais eficaz para o tratamento da osteoporose grave em humanos. .

Objectives: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. Methods: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months ofage. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 뀅g/kg, i.v. single dose); (4) OVX + ZOL (50 뀅g/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 뀅g/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. Results: Combined treatment with ZOL plus PRO corrected the decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected the increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. Conclusion: These data suggest that combined treatment with ZOL plus PRO could be a more effective approach for treating severe osteoporosis in humans. .

The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor / Efeito de esmolol sobre o intervalo QT corrigido e alterações da dispersão do intervalo QT corrigido observadas durante a indução da anestesia em pacientes hipertensos que receberam um inibidor da enzima conversora de angiotensina / Efecto del esmolol sobre el intervalo QT corregido y alteraciones de la dispersión del intervalo QT corregido observadas durante la inducción de la anestesia en pacientes hipertensos que recibieron un inhibidor de la enzima convertidora de la angiotensina

BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500 mcg/kg followed by a 100 mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5 min after esmolol and saline administration, 3 min after the induction and 30 s, 2 min and 4 min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p = 0.012), the corrected-QT interval dispersion interval was longer in the control group (p = 0.034) and the mean heart rate was higher in the control group (p = 0.022) 30 s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p = 0.038). CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin ...

JUSTIFICATIVA E OBJETIVO: É óbvia a importância de minimizar as respostas simpatoadrenérgicas exageradas e o intervalo QT e a dispersão do intervalo QT que podem ocorrer por causa de laringoscopia e intubação traqueal durante a indução da anestesia em pacientes hipertensos. Esmolol diminui a resposta hemodinâmica à laringoscopia e à intubação. Porém, o efeito de esmolol sobre a redução do intervalo QT prolongado e a dispersão do intervalo QT induzida pela laringoscopia e intubação é controverso. Pesquisamos o efeito de esmolol sobre a hemodinâmica e o intervalo QT corrigido e as alterações da dispersão do intervalo QT observadas durante a indução da anestesia em pacientes hipertensos que receberam inibidores da enzima conversora de angiotensina (IECA). MÉTODOS: Foram incluídos no estudo 60 pacientes, estado físico ASA I-II, com hipertensão arterial essencial e que receberam IECA. O grupo esmolol recebeu uma dose em bolus de 500 mcg kg-1, seguida por infusão contínua de 100 mcg kg-1 min-1 até o quarto minuto após a intubação. O grupo controle recebeu solução salina a 0,9%, semelhantemente ao grupo esmolol. Os valores da pressão arterial média e da frequência cardíaca e os registros do eletrocardiograma foram obtidos durante a fase inicial pré-anestesia, cinco minutos após a administração de esmolol e solução salina, três minutos após a indução e 30 segundos, dois minutos e quatro minutos após a intubação. RESULTADOS: O intervalo QT corrigido foi menor no grupo esmolol (p = 0,012), o intervalo de dispersão do intervalo QT corrigido foi maior no grupo controle (p = 0,034) e a frequência cardíaca média foi maior no grupo controle (p = 0,022) 30 segundos após a intubação. O risco da frequência de arritmia foi maior no grupo controle no quarto minuto após a intubação (p = 0,038). CONCLUSÃO: Descobrimos que a intubação traqueal prolonga o intervalo e a dispersão do intervalo QT corrigido e aumenta a frequência cardíaca durante a indução da ...

JUSTIFICACIÓN Y OBJETIVO: Es evidente la importancia que tiene minimizar las respuestas simpatoadrenérgicas exageradas y el intervalo QT y la dispersión del intervalo QT que pueden ocurrir a causa de la laringoscopia e intubación traqueal durante la inducción de la anestesia en pacientes hipertensos. El esmolol disminuye la respuesta hemodinámica a la laringoscopia y a la intubación. Sin embargo, su efecto sobre la reducción del intervalo QT prolongado y la dispersión del intervalo QT inducida por la laringoscopia e intubación es controvertido. Investigamos el efecto del esmolol sobre la hemodinámica y el intervalo QT corregido, y las alteraciones de la dispersión del intervalo QT observadas durante la inducción de la anestesia en pacientes hipertensos que recibieron inhibidores de la enzima convertidora de la angiotensina. MÉTODOS: Fueron incluidos en el estudio 60 pacientes, estado físico ASA I-II, con hipertensión arterial esencial y que recibieron inhibidores de la enzima convertidora de la angiotensina. El grupo esmolol recibió una dosis en bolos de 500 mcg/kg, seguida de infusión continua de 100 mcg/kg/min hasta el cuarto minuto después de la intubación. El grupo control recibió una solución salina al 0,9%, de forma similar al grupo esmolol. Los valores de la presión arterial media y de la frecuencia cardíaca y los registros del electrocardiograma fueron obtenidos durante la fase inicial preanestésica, 5 min después de la administración del esmolol y la solución salina, 3 min después de la inducción, y 30 s, 2 min y 4 min después de la intubación. RESULTADOS: El intervalo QT corregido fue menor en el grupo esmolol (p = 0,012), el intervalo de dispersión del intervalo QT corregido fue mayor en el grupo control (p = 0,034) y la frecuencia cardíaca media fue mayor en el grupo control (p = 0,022) 30 s después de la intubación. El riesgo de la frecuencia de arritmia fue mayor en el grupo control en el cuarto minuto después de la intubación ...

Effect of propranolol on capsular reaction around silicone implants in guinea pigs

PURPOSE: To evaluate the effect of propranolol on capsular architecture around silicone implants by measuring the inflammation, capsular thickness, and collagen fiber density, using a guinea pig experimental model. METHODS: Thirty six adult male guinea pigs randomly divided into two groups (n=18) were used. Each one received a silicone implant with textured-surface. The capsular tissue around implants from untreated or treated animals with the beta-adrenoceptor antagonist propranolol (10 mg/kg, dissolved in daily water) were analyzed for inflammation by histological scoring, capsular thickness by computerized histometry, and collagen fibers type I and Type III density by picrosirius polarization at different time points (7, 14 or 21 days after silicone implantation). RESULTS: Propranolol treatment reduced inflammation and impaired capsular thickness and delayed collagen maturation around the textured implant. CONCLUSION: Propranolol reduces the risk of developing capsular contracture around silicone implants with textured surface. .

Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG-PET in Patients with Essential Tremor According to Their Response to Beta-Blockers

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.

Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

The comparison of the effects of dexmedetomidine, fentanyl and esmolol on prevention of hemodynamic response to intubation / Comparação entre os efeitos de dexmedetomidina, fentanil e esmolol na prevenção da resposta hemodinâmica à intubação / Comparación entre los efectos de la dexmedetomidina, el fentanilo y el esmolol en la prevención de la respuesta hemodinámica a la intubación

Background and objectives: Laryngoscopy and intubation can cause hemodynamic response. Various medications may be employed to control that response. In this study, we aimed to compare the effects of dexmedetomidine, fentanyl and esmolol on hemodynamic response. Methods: Ninety elective surgery patients who needed endotracheal intubation who were in American Society of Anesthesiology I–II group and ages between 21 and 65 years were included in that prospective, randomized, double-blind study. Systolic, diastolic, mean arterial pressures, heart rates at the time of admittance at operation room were recorded as basal measurements. The patients were randomized into three groups: Group I (n = 30) received 1 μg/kg dexmedetomidine with infusion in 10 min, Group II (n = 30) received 2 μg/kg fentanyl, Group III received 2 mg/kg esmolol 2 min before induction. The patients were intubated in 3 min. Systolic, diastolic, mean arterial pressures and heart rates were measured before induction, before intubation and 1, 3, 5, 10 min after intubation. Results: When basal levels were compared with the measurements of the groups, it was found that 5 and 10 min after intubation heart rate in Group I and systolic, diastolic, mean arterial pressures in Group III were lower than other measurements (p < 0.05). Conclusions: Dexmedetomidine was superior in the prevention of tachycardia. Esmolol prevented sytolic, diastolic, mean arterial pressure increases following intubation. We concluded that further studies are needed in order to find a strategy that prevents the increase in systemic blood pressure and heart rate both. .

Justificativa e objetivos: Laringoscopia e intubação podem causar resposta hemodinâmica. Vários medicamentos podem ser usados para controlar essa resposta. Neste estudo, nosso objetivo foi comparar os efeitos de dexmedetomidina, fentanil e esmolol sobre a resposta hemodinâmica. Métodos: Foram incluídos no estudo prospectivo, randômico e duplo-cego 90 pacientes programados para cirurgias eletivas, com intubação endotraqueal, estado físico ASA I-II, entre 21 e 65 anos. Pressões arteriais médias, sistólicas, diastólicas e frequências cardíacas foram medidas ao darem entrada na sala de operações e registradas como valores basais. Os pacientes foram randomizados em três grupos: Grupo I (n = 30) recebeu 1 μg/kg de dexmedetomidina com infusão em 10 min; Grupo II (n = 30) recebeu 2 μg/kg de fentanil; Grupo III (n = 30) recebeu 2 mg/kg de esmolol 2 min antes da indução. Os pacientes foram intubados em 3 min. As pressões médias, sistólicas e diastólicas e as frequências cardíacas foram medidas antes da indução, antes da intubação e nos minutos 1, 3, 5 e 10 após a intubação. Resultados: Quando os níveis basais foram comparados entre os grupos, verificou-se que nos minutos 5 e 10 pós-intubação as frequências cardíacas no Grupo I e as pressões arteriais médias, sistólicas e diastólicas no Grupo III estavam mais baixas do que em outros tempos mensurados (p <0,05 ). Conclusões: Dexmedetomidina foi superior na prevenção de taquicardia. Esmolol preveniu o aumento das pressões arteriais médias, sistólicas e diastólicas após a intubação. Concluímos que estudos adicionais são necessários para descobrir uma estratégia que previna tanto o aumento ...

Justificación y objetivos: La laringoscopia y la intubación pueden causar una respuesta hemodinámica. Varios medicamentos pueden ser usados para controlar esa respuesta. En este estudio, nuestro objetivo fue comparar los efectos de la dexmedetomidina, el fentanilo y el esmolol sobre la respuesta hemodinámica. Métodos: Noventa pacientes programados para cirugías electivas con intubación endotraqueal, estado físico ASA I-II, y edades entre 21 y 65 años, se incluyeron en el estudio prospectivo, aleatorizado y doble ciego. Las presiones arteriales medias, sistólicas, diastólicas y las frecuencias cardíacas se midieron cuando los pacientes llegaron al quirófano y se registraron como valores basales. Los pacientes fueron aleatorizados en 3 grupos: el grupo i (n = 30) recibió 1 μg/kg de dexmedetomidina con infusión en 10 min; el grupo ii (n = 30) recibió 2 μg/kg de fentanilo; el grupo iii recibió 2 mg/kg de esmolol 2 min antes de la inducción. Los pacientes fueron intubados en 3 min. Las presiones medias, sistólicas y diastólicas y las frecuencias cardíacas fueron medidas antes de la inducción, antes de la intubación y durante los minutos 1, 3, 5 y 10 después de la intubación. Resultados: Cuando los niveles basales fueron comparados entre los grupos, verificamos que en los minutos 5 y 10 la postintubación, las frecuencias cardíacas en el grupo i y las presiones arteriales medias, sistólicas y diastólicas en el grupo iii eran más bajas que en otros tiempos medidos (p < 0,05). Conclusiones: La dexmedetomidina fue superior en la prevención de la taquicardia. El esmolol previno el aumento de las presiones arteriales medias, sistólicas y diastólicas después de la intubación. Concluimos que son necesarios algunos estudios adicionales para descubrir una estrategia ...

Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial / Infusão intraoperatória de esmolol reduz o consumo pós-operatório de analgésicos e o uso de anestésico durante a septorrinoplastia: estudo randômico / La infusión intraoperatoria de esmolol reduce el consumo postoperatorio de analgésicos y el uso de anestésico durante la septorrinoplastia: estudio aleatorizado

Background and objectives: Esmolol is known to have no analgesic activity and no anaesthetic properties; however, it could potentiate the reduction in anaesthetic requirements and reduce postoperative analgesic use. The objective of this study is to evaluate the effect of intravenous esmolol infusion on intraoperative and postoperative analgesic consumptions as well as its effect on depth of anaesthesia. Methods: This randomized-controlled double blind study was conducted in a tertiary care hospital between March and June 2010. Sixty patients undergoing septorhinoplasty were randomized into two groups. History of allergy to drugs used in the study, ischaemic heart disease, heart block, bronchial asthma, hepatic or renal dysfunction, obesity and a history of chronic use of analgesic or β-blockers were considered cause for exclusion from the study. Thirty patients received esmolol and remifentanil (esmolol group) and 30 patients received normal saline and remifentanil (control group) as an intravenous infusion during the procedure. Mean arterial pressure, heart rate, and bispectral index values were recorded every 10min. Total remifentanil consumption, visual analogue scale scores, time to first analgesia and total postoperative morphine consumption were recorded. Results: The total remifentanil consumption, visual analogue scale scores at 0, 20 and 60 min, total morphine consumption, time to first analgesia and the number of patients who needed an intravenous morphine were lower in the esmolol group. Conclusions: Intravenous infusion of esmolol reduced the intraoperative and postoperative analgesic consumption, reduced visual analogue scale scores in the early postoperative period and prolonged the time to first analgesia; however it did not influence the depth of anaesthesia. .

Justificativa e objetivos: Esmolol é conhecido por não ter atividade analgésica e propriedades anestésicas; porém, pode potenciar a redução da necessidade de anestésicos e reduzir o uso de analgésicos no pós-operatório. O objetivo deste estudo foi avaliar o efeito da infusão de esmolol por via intravenosa sobre o consumo de analgésico durante os períodos intraoperatório e pós-operatório, bem como seu efeito sobre a profundidade da anestesia. Métodos: Este estudo randômico, controlado e duplo-cego foi conduzido em um hospital terciário entre março e junho de 2010. Foram randomicamente divididos em dois grupos 60 pacientes programados para serem submetidos à septorrinoplastia. História de alergia aos medicamentos usados no estudo, isquemia cardíaca, bloqueio cardíaco, asma brônquica, insuficiência hepática ou renal, obesidade e história de uso crônico de analgésicos ou β-bloqueadores foram os critérios de exclusão. Trinta pacientes receberam esmolol e remifentanil (grupo esmolol) e 30 receberam soro fisiológico e remifentanil (grupo controle) via perfusão intravenosa. Pressão arterial média, frequência cardíaca e valores do índice bispectral foram registrados a cada 10 minutos. Consumo total de remifentanil, escores da escala visual analógica, tempo para a primeira analgesia e consumo total de morfina no pós-operatório foram registrados. Resultados: O consumo total de remifentanil, os escores da escala visual analógica nos minutos 0, 20 e 60, o consumo total de morfina, o tempo para a primeira analgesia e o número de pacientes que precisaram de morfina intravenosa foram menores no grupo esmolol. Conclusões: Esmolol em infusão intravenosa reduziu o consumo de analgésicos tanto no intraoperatório ...

Justificación y objetivos: El esmolol se conoce porque no posee actividad añalgésica ni propie-dades anestésicas; sin embargo, puede potenciar la reducción de la necesidad de anestésicos y disminuir el uso de analgésicos en el postoperatorio. El objetivo de este estudio fue evaluar el efecto de la infusión de esmolol por vía intravenosa sobre el consumo de analgésico durante los períodos intraoperatorio y postoperatorio, como también su efecto sobre la profundidad de la anestesia. Métodos: Este estudio aleatorizado, controlado y doble ciego fue llevado a cabo en un hospital terciario entre marzo y junio de 2010. Sesenta pacientes programados para someterse a la septorrinoplastia fueron aleatoriamente divididos en 2 grupos. El historial de alergia a los medicamentos usados en el estudio, isquemia cardíaca, bloqueo cardíaco, asma bronquial, insuficiencia hepática o renal, obesidad e historial de uso crónico de analgésicos o ß-bloqueantes, fueron los criterios de exclusión del estudio. Treinta pacientes recibieron esmolol y remifenta-nilo (grupo esmolol) y 30 pacientes recibieron suero fisiológico y remifentanilo (grupo control), vía perfusión intravenosa durante el procedimiento. La presión arterial media, frecuencia cardíaca y valores del índice biespectral fueron registrados cada 10 min. Se registraron el consumo total de remifentanilo, puntuaciones de la escala visual analógica, tiempo para la primera analgesia y el consumo total de morfina en el postoperatorio. Resultados: El consumo total de remifentanilo, las puntuaciones de la escala visual analógica en los minutos 0, 20 y 60, el consumo total de morfina, el tiempo para la primera analgesia y el número de pacientes que necesitaron morfina intravenosa fueron menores en el grupo esmolol. Conclusiones: El esmolol en infusión intravenosa ...

Adrenaline; the effects in presence of beta blocker in isolated mammalian heart

There is no doubt that the effects of the catecholamines of the heart are mainly due to the stimulation of beta-adrenoceptors but in the mid 1960' s the first evidence was presented that a-adrenoceptors mediating positive inotrpoism exists also in the myocardium beside well established beta -adrenoceptors. In our observation adrenaline shows a positive inotropic response. The response of adrenaline in presence of metoprolol [beta1blocker] showed negative inotropic effect

current status of beta blockers' use in the management of hypertension

The invention of beta -blockers culminated in a new era in the treatment of cardiovascular diseases [CD], and changed the course of pharmacology research for years to come. Since the introduction of propranolol into clinical practice in 1964, beta -blockers enjoyed a special place in the clinicians' armamentarium against CDs, especially for patients with ischemic heart diseases, and are still one of the most extensively used therapeutic drugs in both cardiac and non-cardiac ailments. Current uses of beta -blockers in CDs include ischemic heart diseases, hypertension, cardiac arrhythmias, and heart failure. Other substantial non-cardiac uses include glaucoma, migraine, situational anxiety, benign essential tremors, and cardiac symptoms of thyrotoxicosis. This review covers some of the evolutionary changes of clinical uses of beta -blockers, the rationale for their use, some recent controversies surrounding their use for treatment of hypertension, and advantages of newer additions to the group

O carvedilol potencializa o efeito antioxidante das vitaminas E e C na cardiopatia chagásica crônica / Carvedilol enhances the antioxidant effect of vitamins E and C in chronic chagas heart disease

FUNDAMENTO: A doença de Chagas continua a ser uma importante doença endêmica no país, sendo o acometimento cardíaco a sua manifestação mais grave. OBJETIVO: Verificar se o uso concomitante de carvedilol potencializará o efeito antioxidante das vitaminas E e C na atenuação do estresse oxidativo sistêmico na cardiopatia chagásica crônica. MÉTODOS: Foram estudados 42 pacientes com cardiopatia chagásica, agrupados de acordo com a classificação modificada de Los Andes, em quatro grupos: 10 pacientes no grupo IA (eletrocardiograma e ecocardiograma normais: sem envolvimento do coração), 20 pacientes do grupo IB (eletrocardiograma normal e ecocardiograma anormal: ligeiro envolvimento cardíaco), oito pacientes no grupo II (eletrocardiograma e ecocardiograma anormais, sem insuficiência cardíaca: moderado envolvimento cardíaco) e quatro pacientes no grupo III (eletrocardiograma e ecocardiograma anormais com insuficiência cardíaca: grave envolvimento cardíaco). Os marcadores de estresse oxidativo foram medidos no sangue, antes e após um período de seis meses de tratamento com carvedilol e após seis meses de terapia combinada com vitaminas E e C. Os marcadores foram: atividades da superóxido dismutase, catalase, glutationa peroxidase, glutationa S-transferase e redutase, mieloperoxidase e adenosina deaminase, e os níveis de glutationa reduzida, de espécies reativas do ácido tiobarbitúrico, proteína carbonilada, vitamina E e óxido nítrico. RESULTADOS: Após o tratamento com carvedilol, todos os grupos apresentaram diminuições significativas dos níveis de proteína carbonilada e glutationa reduzida, enquanto os níveis de óxido nítrico e atividade da adenosina aumentaram significativamente apenas no grupo menos acometido (IA). Além disso, a maioria das enzimas antioxidantes mostrou atividades diminuídas nos grupos menos acometidos (IA e IB). Com a adição das vitaminas ao carvedilol houve diminuição dos danos em proteínas, nos níveis de glutationa e na maior parte da atividade das enzimas antioxidantes. CONCLUSÕES: A queda dos níveis de estresse oxidativo, verificada pelos marcadores testados, foi mais acentuada quando da associação do fármaco carvedilol com as vitaminas antioxidantes. Os dados sugerem que tanto o carvedilol isoladamente como sua associação com as vitaminas foram eficazes em atenuar o dano oxidativo sistêmico em pacientes com CC, especialmente aqueles menos acometidos, sugerindo a possibilidade de sinergismo entre esses compostos.

BACKGROUND: Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. OBJECTIVE: To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. METHODS: A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. RESULTS: After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. CONCLUSIONS: The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.

Effects of Cardioselective Beta Blocker Nebivolol on Different Biochemical Parameters in Essential Hypertensive Patients.

Background : Nebivolol is a third-generation highly selective b1-blocker with additional endothelial nitric oxide (NO) mediated vasodilating activity. This property may potentiate the blood pressure-lowering effect of Nebivolol. Nebivolol is also claimed to have neutral or favourable effect on carbohydrate metabolism and lipid profile. Therefore this study was conducted to evaluate effects of Nebivolol on different biochemical parameters in essential hypertensive patients. Materials and Methods : 21 newly diagnosed patients of either sex with essential hypertension were included in the study. Patients having co-morbidities e.g. Diabetes mellitus, hyperlipidemia, gout, pregnant females were excluded from the study. Baseline readings of lipid profile, serum electrolytes, fasting blood sugar and uric acid were recorded before starting Nebivolol drug therapy. Same biochemical tests were repeated after six months drug treatment. Results and Observation : After comparing the means there is increase in total cholesterol, LDL, Serum electrolytes, blood sugar levels but this increase is within normal limits and is not statistically significant. While there is decrease in TG level but statistically not significant. No significant change in HDL, uric acid levels. Conclusion : Nebivolol is a unique, highly selective b1-blocker due to its neutral metabolic properties and is potentially safe over conventional b-blockers.