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.

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.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft / Comparação de esmolol em bolus e infusão contínua na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária / Comparación del esmolol en bolos e infusión continua en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria

BACKGROUND AND OBJECTIVE: The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. METHODS: After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5 mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5 mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. RESULTS: While area under curve (AUC) (SAP × time) was being found more in Group B and C than Group I, AUC (SAP × T int and T st) and AUC (SAP × T2) was found more in Group B and C than Group I (p < 0.05). Moreover AUC (HR × T st) was found less in Group B than Group C but no significant difference was found between Group B and Group I. CONCLUSION: This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery. .

JUSTIFICATIVA E OBJETIVO: o objetivo deste estudo prospectivo, randômico e duplo-cego foi investigar os efeitos do uso diferente de esmolol na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária. MÉTODOS: após obter a aprovação do Comitê de Ética local e consentimento informado assinado pelos pacientes, 45 pacientes foram randomicamente divididos em três grupos. O Grupo I (infusão) recebeu 0,5 mg/kg/min de esmolol em infusão a partir de 10 min antes da intubação até 5 minutos após a esternotomia; o Brupo B (bolus) recebeu 1,5 mg/kg de esmolol em bolus IV a partir de 2 min antes da intubação e esternotomia; o grupo C (controle) recebeu NaCl a 0,9%. Todos os parâmetros demográficos foram registados. Os valores de frequência cardíaca e pressão arterial foram registrados desde antes da infusão até a indução da anestesia a cada minuto, durante a intubação endotraqueal, a cada minuto durante 10 min após a intubação endotraqueal e antes, durante e após a esternotomia no primeiro e quinto minutos. RESULTADOS: enquanto a área sob a curva (ASC) (SAP × tempo) foi maior nos grupos B e C que no Grupo I, a ASC (SAP × T int e T st) e ASC (SAP × T2) foram maiores nos grupos B e C que no Grupo I (p < 0,05). Além disso, a ASC (FC × T st)) foi menor no Grupo B que no Grupo C, mas não houve diferença significante entre os grupos B e I. CONCLUSÃO: este estudo destaca que a administração de esmolol em infusão é mais eficaz que em bolus para controlar a pressão arterial sistólica durante a intubação endotraqueal e esternotomia em CRC. .

JUSTIFICACIÓN Y OBJETIVO: el objetivo de este estudio prospectivo, aleatorizado y doble ciego fue investigar los efectos del diferente uso del esmolol en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria. MÉTODOS: después de obtener la aprobación del Comité de Ética local y el consentimiento informado firmado por los pacientes, 45 de ellos fueron aleatoriamente divididos en 3 grupos. El grupo I (infusión) recibió 0,5 mg/kg/min de esmolol en infusión desde 10 min antes de la intubación hasta 5 min después de la esternotomía; el grupo B (bolo), que recibió 1,5 mg/kg de esmolol en bolo iv a partir de 2 min antes de la intubación y esternotomía; el grupo C (control) recibió NaCl al 0,9%. Todos los parámetros demográficos fueron registrados. Los valores de frecuencia cardíaca y presión arterial fueron registrados ya antes de la infusión y hasta la inducción de la anestesia cada minuto durante la intubación endotraqueal, cada minuto durante 10 min después de la intubación endotraqueal, y antes, durante y después de la esternotomía en el primer y quinto minutos. RESULTADOS: mientras que el área bajo la curva (AUC) (presión arterial sistólica [PAS] × tiempo) fue mayor en los grupos B y C que en el grupo I, el AUC (PAS ×T int y T st ) y AUC (PAS × T 2 ) fueron mayores en los grupos B y C que en el grupo I (p < 0,05). Además, el AUC (frecuencia cardíaca × T st ) fue menor en el grupo B que en el grupo C, pero no hubo diferencia significativa entre los grupos B e I. CONCLUSIÓN: este estudio destaca que la administración del esmolol en infusión es más eficaz que en bolos para controlar la PAS durante la intubación endotraqueal ...

The effects of carvedilol on ischemia-reperfusion injury in the rat testis

Objective: To analyze the oxidative damage and histopathological alterations caused by ischemia-reperfusion (I/R) injury and ameliorative effects of carvedilol (CVD) in the rat testis. Materials and Methods: Twenty-one male rats were randomized into 3 groups as follows: Group I (n = 7); control (sham) group, Group II (n = 7); I/R group, in which I/R injury was performed by torsing the left testis 720º clockwise for 2 hours and detorsing for 2 hours. Group III (n = 7); CVD treatment group; in addition to I/R process, one-dose of CVD was administered (2mg/kg, i.p) 30 min. before detorsion. Levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and levels of malondialdehyde (MDA) and protein carbonyl (PC) were determined in testicular tissues and serum of rats. Testicular tissues were also examined histopathologically and Johnsen scores were determined. Results: Activities of SOD and GSH-Px in serum and testicular tissues were increased by I/R, but administration of CVD decreased these levels (p < 0.001 and p = 0.001). Significantly increased MDA levels in serum and testicular tissues were decreased by CVD treatment (p < 0.001 and p = 0.001). Concerning PC levels in serum and testicular tissues, there was no statistically significant difference between the groups (p = 0.989 and p = 0.428). There was not a statistically significant difference in terms of mean Johnsen scores between the groups (p = 0.161). Conclusions: Administration of CVD decreased oxidative damage biochemically in the rat testis caused by I/R injury, but histopathologically no change was observed between all of the groups. .

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.

Efeitos de esmolol, lidocaína e fentanil nos intervalos dispersão da onda P, QT, QTc e respostas hemodinâmicas à intubação endotraqueal durante indução com propofol: um estudo comparativo / Effects of esmolol, lidocaine and fentanyl on P wave dispersion, QT, QTc intervals and hemodynamic responses to endotracheal intubation during propofol induction: a comparative study / Efectos del esmolol, de la lidocaína y del fentanilo en los intervalos dispersión de la onda, QT, QTc y respuestas hemodinámicas a la intubación endotraqueal durante inducción con propofol: un estudio comparativo

JUSTIFICATIVA E OBJETIVOS: Investigar o efeito de esmolol, lidocaína e fentanil na dispersão da onda P (DP), durações dos intervalos QT e QT corrigido (QTc) e as respostas hemodinâmicas à intubação endotraqueal durante a indução com propofol. MÉTODOS: Foram incluídos 80 pacientes adultos, estado físico ASA I ou II, idade entre 18 e 60 anos, neste estudo prospectivo, randômico e duplo-cego. Todos os pacientes foram submetidos a exame eletrocardiográfico (ECG) antes da indução da anestesia. Os pacientes foram randomicamente alocados em quatro grupos iguais. O grupo controle (Grupo C) recebeu 5 mL de solução salina; o grupo esmolol (Grupo E) recebeu 0,5 mg.kg-1 de esmolol; o grupo fentanil (Grupo F) recebeu 2 µg.kg-1 de fentanil e o grupo lidocaína (Grupo L) recebeu 1,5 mg.kg-1 de lidocaína antes da indução anestésica. A anestesia foi induzida com propofol. ECG foi feito em todos os pacientes durante o primeiro e o terceiro minutos de indução, 3 minutos após a administração de relaxante muscular e 5 e 10 minutos após intubação. A DP e intervalos QT foram medidos em todos os ECGs. Os intervalos QTc foram determinados com o uso da fórmula de Bazett. Frequência cardíaca (FC) e pressão arterial média (PAM) foram registradas antes e depois da indução anestésica, imediatamente após a intubação e em 1, 3, 5, 7 e 10 minutos após a intubação. RESULTADOS: Após a intubação, a FC aumentou significativamente nos Grupos C, L e F em comparação com o grupo controle. Porém, não houve diferença significativa nos valores da FC após a intubação entre os grupos E e controle. Nos Grupos C e L, a PAM aumentou significativamente após a intubação em comparação com o grupo controle. No entanto, nos Grupos L, F e E não houve diferença significativa entre os valores da PAM após a intubação em comparação com o grupo controle. A DP foi significativamente mais longa no Grupo C após a intubação em comparação com o grupo controle. Porém, nos grupos L, F e E não houve diferença significativa entre os valores de DP após a intubação em comparação com o grupo controle. A duração do intervalo QTc foi significativamente maior nos grupos C e L após a intubação em comparação com o grupo controle. Porém, não houve diferença significativa na duração do QTc nos grupos F e E após a intubação em comparação com o grupo controle. CONCLUSÃO: Concluímos que a administração de esmolol antes da intubação previne a taquicardia, o aumento da PAM e as durações da onda P e intervalo QTc causados pela laringoscopia e intubação traqueal.

BACKGROUND AND OBJECTIVES: In our study we aimed to investigate the effect of esmolol, lidocaine and fentanyl on P-wave dispersion (Pwd), QT and corrected QT (QTc) durations and hemodynamic responses to endotracheal intubation during propofol induction. METHODS: A total of eighty adult patients, American Society of Anesthesiologists (ASA) Physical Status I or II aged 18 to 60 years were included in this prospective, randomised, double-blind study. All patients had control electrocardiograms (ECGs) done before anesthesia induction. The patients were randomised into four equal groups. The control group (Group C) received saline 5 mL, the esmolol group (Group E) received esmolol 0.5 mg.kg-1, the fentanyl group (Group F) received fentanyl 2 µg.kg-1 and the lidocaine group (Group L) received lidocaine 1.5 mg.kg-1 before anesthesia induction. Anesthesia was induced with intravenous propofol. ECGs for all patients were performed during the 1st and 3rd minutes of induction, 3 minutes after administration of muscle relaxant, and at 5 minutes and 10 minutes after intubation. Pwd and QT intervals were measured on all ECGs. QTc intervals were determined using the Bazett formula. Heart rate (HR) and mean arterial pressure (MAP) were recorded before and after induction of anesthesia, immediately after intubation, and 1, 3, 5, 7 and 10 minutes after intubation. RESULTS: Compared with control, HR significantly increased in Group C, Group L and Group F after intubation. However, in Group E, there was no significant difference in HR values between control and after intubation. Compared with control, MAP significantly increased in Group C and Group L after the intubation. However, in Group E and Group F, there was no significant difference in MAP values between control and after the intubation. Compared with control, Pwd significantly increased in Group C after intubation. In Group L, Group F and Group E, there was no significant difference in Pwd values between control and after the intubation. Compared with control, QTc duration significantly increased in Group C and L after the intubation. In Group F and Group E, there was no significant difference in QTc durations between control and after the intubation. CONCLUSION: We concluded that administration of esmolol before intubation prevents tachycardia and an increase in MAP, Pwd and QTc duration caused by laryngoscopy and tracheal intubation.

JUSTIFICATIVA Y OBJETIVOS: Investigar el efecto del esmolol, lidocaína y fentanilo en la dispersión de la onda P (DOP), duraciones de los intervalos QT y QT corregido (QTc) y las respuestas hemodinámicas a la intubación endotraqueal durante la inducción con propofol. MÉTODOS: En este estudio prospectivo, aleatorio y doble ciego, fueron incluidos 80 pacientes adultos, con estado físico ASA I o II, y edad entre 18 y 60 años. Todos los pacientes se sometieron al examen electrocardiográfico (ECG) antes de la inducción de la anestesia. Los pacientes fueron aleatoriamente divididos en cuatro grupos iguales. El grupo control (Grupo C) recibió 5 mL de solución salina; el grupo esmolol (Grupo E) recibió 0,5 mg.kg-1 de esmolol; el grupo fentanilo (Grupo F) recibió 2 µg.kg-1 de fentanilo y el grupo lidocaína (Grupo L) recibió 1,5 mg.kg-1 de lidocaína antes de la inducción anestésica. La anestesia fue inducida con propofol. El ECG se hizo en todos los pacientes durante el primero y el tercer minuto de inducción, 3 minutos después de la administración del relajante muscular y 5 y 10 minutos después de la intubación. La DOP y los intervalos QT se midieron en todos los ECGs. Los intervalos QTc fueron determinados con el uso de la fórmula de Bazett. La frecuencia cardíaca (FC) y la presión arterial promedio (PAP) fueron registradas antes y después de la inducción anestésica, inmediatamente después de la intubación y en 1, 3, 5, 7 y 10 minutos después de la intubación. RESULTADOS: Después de la intubación, la FC aumentó significativamente en los Grupos C, L y F en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en los valores de la FC después de la intubación entre los grupos E y control. En los Grupos C y L, la PAP aumentó significativamente después de la intubación en comparación con el grupo control. Sin embargo, en los Grupos L, F y E no hubo diferencia significativa entre los valores de la PAP posteriormente a la intubación en comparación con el grupo control. La DOP fue significativamente más larga en el Grupo C después de la intubación en comparación con el grupo control. No obstante, en los grupos L, F y E no hubo diferencia significativa entre los valores de DOP después de la intubación en comparación con el grupo control. La duración del intervalo QTc fue significativamente mayor en los grupos C y L después de la intubación en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en la duración del QTc en los grupos F y E después de la intubación en comparación con el grupo control. CONCLUSIONES: Llegamos entonces a la conclusión, de que la administración del esmolol antes de la intubación previene la taquicardia, el aumento de la PAP y las duraciones de la onda P e intervalo QTc causados por la laringoscopia y por la intubación traqueal.

Carvedilol atenua o estresse oxidativo na cardiopatia chagásica crônica / Carvedilol attenuates oxidative stress in chronic chagasic cardiomyopathy / Carvedilol atenúa el estrés oxidativo en la cardiopatía chagásica crónica

FUNDAMENTO: Há cada vez mais evidências sugerindo que doença de Chagas envolve dano oxidativo e contribui para a progressão da doença cardíaca. OBJETIVO: Avaliar o efeito do carvedilol sobre marcadores de estresse oxidativo na doença de Chagas crônica. MÉTODOS: A população de estudo incluiu 42 pacientes com cardiopatia chagásica e os biomarcadores de estresse oxidativo foram medidos antes e após um período de seis meses de tratamento com carvedilol (37,5 mg/dia). Os pacientes foram considerados de acordo com a classificação de Los Andes, e a atividade da superóxido dismutase, catalase, glutationa peroxidase, S-transferase e redutase, mieloperoxidase e adenosina deaminase; e os níveis de glutationa reduzida, de espécies reativas do ácido tiobarbitúrico, proteína carbonil, vitamina E e óxido nítrico foram medidos no sangue. RESULTADOS: Após o tratamento com carvedilol, todos os grupos apresentaram reduções significativas nos níveis de proteína carbonil e glutationa reduzida, enquanto os níveis de óxido nítrico e atividade da adenosina aumentaram significativamente somente no grupo IA. Além disso, a maioria das enzimas antioxidantes apresentou diminuição de suas atividades, nos grupos IA e IB. CONCLUSÃO: Os dados sugerem que o tratamento com carvedilol foi eficaz na atenuação do dano oxidativo, um efeito que pode ser particularmente importante em doença de Chagas crônica com cardiopatia.

BACKGROUND: There is increasing evidence suggesting that Chagas disease involves oxidative damage and contributes to heart disease progression. OBJECTIVE: To evaluate the effect of carvedilol on oxidative stress markers in chronic Chagas disease. METHODS: The study population included 42 patients with Chagas cardiomyopathy and oxidative stress biomarkers were measured before and after a period of six months of treatment with carvedilol (37.5 mg/day). Patients were considered according to the Los Andes classification and the activity of superoxide dismutase, catalase, glutathione peroxidase, S-transferase and reductase, myeloperoxidase and adenosine deaminase; levels of reduced glutathione, thiobarbituric acid reactive species, carbonyl protein, vitamin E and nitric oxide were measured in blood. RESULTS: After treatment with carvedilol, all groups showed significant reductions in levels of carbonyl protein and reduced glutathione, whereas the levels of nitric oxide and adenosine activity increased significantly only in group IA. Moreover, most of the antioxidant enzymes showed decrease in activity in groups IA and IB. CONCLUSION: The data suggest that treatment with carvedilol was effective in attenuating oxidative damage, an effect that may be particularly important in patients with chronic Chagas' disease cardiomyopathy.

FUNDAMENTO: Hay cada vez más evidencias sugiriendo que la enfermedad de Chagas envuelve daño oxidativo y contribuye a la progresión de la enfermedad cardíaca. OBJETIVO: Evaluar el efecto del carvedilol sobre marcadores de estrés oxidativo en la enfermedad de Chagas crónica. MÉTODOS: La población de estudio incluyó 42 pacientes con cardiopatía chagásica y los biomarcadores de estrés oxidativo fueron medidos antes y después de un período de seis meses de tratamiento con carvedilol (37,5 mg/día). Los pacientes fueron considerados de acuerdo con la clasificación de Los Andes, y la actividad de la superóxido dismutasa, catalasa, glutatión peroxidasa, S-transferasa y reductasa, mieloperoxidasa y adenosina deaminasa; y los niveles de glutatión reducida, de especies reactivas del ácido tiobarbitúrico, proteína carbonil, vitamina E y óxido nítrico fueron medidos en la sangre. RESULTADOS: Después del tratamiento con carvedilol, todos los grupos presentaron reducciones significativas en los niveles de proteína carbonil y glutatión reducida, mientras que los niveles de óxido nítrico y actividad de la adenosina aumentaron significativamente solamente en el grupo IA. Además de eso, la mayoría de las enzimas antioxidantes presentó disminución de sus actividades, en los grupos IA e IB. CONCLUSIONES: Los datos sugieren que el tratamiento con carvedilol fue eficaz en la atenuación del daño oxidativo, un efecto que puede ser particularmente importante en enfermedad de Chagas crónica con cardiopatía.

Involvement of β3-adrenergic receptors in the control of food intake in rats

This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of β3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.

comparative study of efficacy of esmolol and fentanyl for pressure attenuation during laryngoscopy and endotracheal intubation

To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation. Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C [control] receiving 10 ml normal saline, group E [esmolol] receiving bolus dose of esmolol 2 mg/kg and group F [fentanyl] receiving bolus dose of fentanyl 2microg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter. Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E. Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol

Associação de betabloqueadores e treinamento físico na insuficiência cardíaca de camundongos / Association of physical training with beta-blockers in heart failure in mice / Asociación de betabloqueantes y entrenamiento físico en la insuficiencia cardíaca de ratones

FUNDAMENTO: O tratamento da insuficiência cardíaca (IC) conta atualmente com diversos tipos de intervenções. Dentre elas, destacam-se a terapia com betabloqueadores (BB) e o treinamento físico (TF). Contudo, os efeitos da associação dessas terapias são pouco estudados. OBJETIVO: Verificar os efeitos do tratamento com BB, metoprolol (M) e carvedilol (C) associados ao TF na IC em camundongos. MÉTODOS: Utilizamos modelo genético de IC induzida em camundongos por hiperatividade simpática. Inicialmente, dividimos os animais com IC em: sedentários (S); treinados (T); tratados com M (138 mg/kg) (M) ou C (65 mg/kg) (C). Na segunda parte, dividimos os grupos em S; treinado e tratado com M (MT) e treinado e tratado com C (CT). O TF consistiu em treinamento aeróbico em esteira por 8 semanas. A tolerância ao esforço foi avaliada por teste progressivo máximo e a fração de encurtamento foi avaliada (FE) por ecocardiografia. O diâmetro dos cardiomiócitos e a fração de colágeno foram avaliados por meio de análise histológica. Os dados foram comparados por ANOVA de um caminho com post hoc de Duncan. O nível de significância foi considerado p < 0,05. RESULTADOS: Destacando FE e remodelação cardíaca, verificamos que, isoladamente, T, M e C apresentaram melhora das variáveis. Na associação, após o período de intervenção, observamos aumento da tolerância ao esforço em MT e CT (43,0 por cento e 33,0 por cento, respectivamente). Houve também redução do diâmetro dos cardiomiócitos (10,0 por cento e 9,0 por cento, respectivamente) e da fração de colágeno (52,0 por cento e 63,0 por cento), após a intervenção. Porém, somente CT melhorou significantemente a FE. CONCLUSÃO: A associação do TF às terapias com M ou C proporcionou benefícios sobre a função e remodelação cardíaca em camundongos com IC.

BACKGROUND: Currently there are several types of interventions for the treatment of heart failure (HF). Among these are beta-blocker therapy (BB) and physical training (PT). However, the effects of the combination of these therapies are poorly studied. OBJECTIVE: To investigate the effects of BB treatment with metoprolol (M) and carvedilol (C) associated with PT in mice with HF. METHODS: We used a genetic model of sympathetic hyperactivity-induced heart failure in mice. Initially, we divided the HF animals into three groups: sedentary (S); trained (T); treated with M (138 mg/kg) (M); or C (65 mg/kg) (C). In the second part, we divided the groups into three subgroups: sedentary (S); trained and treated with M (TM); and trained and treated with C (CT). The PT consisted of aerobic training on a treadmill for 8 weeks. Exercise tolerance was assessed by maximal graded test, and fractional shortening (FS) was assessed by echocardiography. Cardiomyocyte diameter and collagen volume fraction were evaluated by histological analysis. Data were compared by one way ANOVA and post hoc Duncan test. The significance level was set at p < 0.05. RESULTS: As to FS and cardiac remodeling, we found that, in isolation, T, M, and C showed an improvement of the variables analyzed. As to therapy combination, after the intervention period, we observed an increase in exercise tolerance in MT and CT (43.0 percent and 33.0 percent respectively). There was also a reduction in cardiomyocyte diameter (10.0 percent and 9.0 percent respectively) and in collagen volume fraction (52.0 percent and 63.0 percent) after the intervention. However, only CT significantly improved FS. CONCLUSION: The association of PT with M or C therapies provided benefits on cardiac function and remodeling in HF mice.

FUNDAMENTO: El tratamiento de la insuficiencia cardiaca (IC) cuenta actualmente con diversos tipos de intervenciones. De entre ellas podemos destacar la terapia con betabloqueantes (BB) y el entrenamiento físico (EF). Con todo, los efectos de la asociación de estas terapias son poco estudiados. OBJETIVO: Verificar los efectos del tratamiento con BB, metoprolol (M) y carvedilol (C) asociados al EF en la IC en ratones. MÉTODOS: Utilizamos modelo genético de IC inducida en ratones por hiperactividad simpática. Inicialmente, dividimos los animales con IC en: sedentarios (S); entrenados (E); tratados con M (138 mg/kg) (M) o C (65 mg/kg) (C). En la segunda parte, dividimos los grupos en S; entrenado y tratado con M (ME) y entrenado y tratado con C (CE). El EF consistió en entrenamiento aeróbico en estera por 8 semanas. La tolerancia al esfuerzo se evaluó por prueba progresivo máxima y la fracción de acortamiento se evaluó (FE) por ecocardiografía. El diámetro de los cardiomiocitos y la fracción de colágeno fueron evaluados por medio de análisis histológico. Los dados fueron comparados por ANOVA de un camino con post hoc de Duncan. El nivel de significancia se consideró como p < 0,05. RESULTADOS: Destacando FE y remodelación cardíaca, verificamos que, aisladamente, E, M y C presentaron mejora de las variables. En la asociación, tras el período de intervención, observamos aumento de la tolerancia al esfuerzo en ME y CE (el 43 por ciento y el 33 por ciento, respectivamente). Hubo también reducción del diámetro de los cardiomiocitos (el 10 por ciento y el 9 por ciento, respectivamente) y de la fracción de colágeno (el 52 por ciento y el 63 por ciento), tras la intervención. Sin embargo, solamente CE mejoró significantemente la FE. CONCLUSIÓN: La asociación del EF a las terapias con M o C proporcionó beneficios sobre la función y remodelación cardíaca en ratones con IC.

Control of tachycardia and hypertension following coronary artery bypass graft surgery: efficacy and haemodynamic effects of esmolol.

Hypertension following coronary artery bypass grafting is not uncommon, especially in patients having good left ventricular function. It is often accompanied by tachycardia. The purpose of this study is to determine the efficacy of esmolol in the treatment of tachycardia and hypertension immediately following cardiopulmonary bypass and to study other haemodynamic effects of esmolol. Thirty patients undergoing elective [corrected] coronary artery bypass grafting were included in this prospective study. Morphine-based anaesthetic technique along-with standard bypass techniques were used in all the patients. The study was performed in the operating room about 30-45 minutes after the termination of cardiopulmonary bypass. Patients having a heart rate of more than 90 bpm and systolic blood pressure of more than 130 mm Hg without any inotropic support were included and randomly assigned to esmolol or control group. Esmolol was administered in a bolus dose of 500 micrograms/kg followed by infusion of upto 100 micrograms/kg/min. The patients in the control group were administered comparable volumes of normal saline. Baseline haemodynamic measurements were obtained just before the administration of esmolol or normal saline and were repeated after 5, 10, 15, 30 and 45 min. The baseline measurement in both the groups showed that patients were maintaining a state of hyperdynamic circulation with high systolic blood pressure (esmolol group 148 +/- 15 mm Hg, control group 140 +/- 8 mm Hg; p = NS), heart rate (esmolol group 128 +/- 17 bpm, control group 127 +/- 17 bpm; p = NS) and cardiac index (esmolol group 3.1 +/- 1 L/min/m2, control group 3.3 +/- 0.5 L/min/m2; p = NS). Esmolol decreased systolic blood pressure (p < 0.001), heart rate (p < 0.01) and cardiac index (p < 0.05) at five minutes. These changes persisted throughout the study period. The left ventricular stroke work index decreased at five minutes (p < 0.05) and remained so till 30 minutes. The maximum fall in heart rate (15%) and systolic blood pressure (16%) was observed at 45 minutes. There were no haemodynamic changes in the control group except that cardiac index, stroke volume and left ventricular stroke work index increased at five minutes. We conclude that esmolol lowers the indices of cardiovascular work in patients who demonstrated hyperdynamic circulation. This was achieved by decreasing the heart rate and systolic blood pressure which was accompanied by decrease in cardiac index and left ventricular stroke work index.

Comparative study of beta-adrenoceptor blocking efficacy of two formulations of esmolol in vivo and in vitro.

The objective of the present study was to compare the cardiovascular beta-blocking activity of two different formulations of esmolol. Spontaneously beating guinea-pig isolated atria and the heart rate and blood pressure of anaesthetized cat were employed in the study to compare the beta-blocking efficacy of the two formulations of esmolol using isoprenaline as an agonist. In guinea-pig isolated atria the standard esmolol formulation (Brevibloc) reduced basal atrial rate more significantly than the indigenously formulated esmolol (test formulation). Both the formulations produced similar parallel rightward shift of cumulative concentration response curves of isoprenaline with closely comparable pA2 values. In anaesthetized cats, only indigenous esmolol formulation significantly decreased basal heart rate. Both the formulations did not modify the basal blood pressure and isoprenaline-induced fall in blood pressure, despite significantly blocking isoprenaline-induced tachycardia. It is suggested that both the formulations produced similar degree of beta-1 adrenoceptor blocking activity.

Memory-impairing effects of local anesthetics in an elevated plus-maze test in mice

Post-training intracerebroventricular administration of procaine (20 mug/mul) and dimethocaine (10 or 20 mug/mul), local anesthetics of the ester class, prolonged the latency(s) in the retention test of male and female 3-month-old Swiss albino mice (25-35 g body weight; N=140) in the elevated plus-maze (mean + SEM for 10 male mice: control= 41.2 + 8.1; procaine = 78.5 + 10.3; 10 mug/mul dimethocaine = 58.7 + 12.3; 20 mug/mul dimethocaine = 109.6 + 5.73; for 10 female mice: control = 34.8 + 5.8; procaine = 55.3 + 13.4; 10 mug/mul dimethocaine = 59.9 + 12.3 and 20 mug/mul dimethocaine = 61.3 + 11.1). However, lidocaine (10 or 20 mug/mul), an amide class type of local anesthetic, failed to influence this parameter. Local anesthetics at the dose range used did not affect the motor coordination of mice exposed to the rota-rod test. These results suggest that procaine and dimethocaine impair some memory process(es) in the plus-maze test. These findings are interpreted in terms of non-anesthetic mechanisms of action of these drugs on memory impairment and also confirm the validity of the elevated plusmaze for the evaluation of drugs effecting learning and memory in mice.

Utilizaçäo do AMP (2-amino-2-metil-1-propanol) em substituiçäo à DEA (Dietanolamina) na dosagem de fosfato inorgânico no soro e urina pelo método direto de NCL / The use of amp (2-amino-2-methyl-1-propanol) as a substitute of DEA (Diethanolamine) in the determination of inorganic phosphate ins erum and urine, by the MCL direct method

O emprego do AMP (2-amino-2-metil-1-propanol) é proposto como substituto da DEA (Dietanolamina) na determinaçäo de fosfato inorgânico no soro na urina, pelo método direto MCL (Mendes eta al., 1988) Este reagente é mais estável em condiçöes de armazenamento e possui alto poder de solubilizaçäo do precipitado de fosfomolibdato. A análise dos resultados demonstrou uma excelente correlaçäo linear, concluindo que o AMP preenche todos os requisitos necessários para seu emprego na determinacäo de fosfato inorgânico

Bunitrolol en hipertension esencial / Bunitrolol in essential hypertension

Estudio de los efectos de la terapia oral con este nuevo agente bloqueador betaadrenergico, con actividad betamimetica intrinseca, en dosis entre 10 y 40 mg al dia, durante un lapso de 16 semanas en diez pacientes hipertensos

Clinical evaluation of 'tenormin' [atenolol] in hypertension

An open 4 week study for evaluating the efficacy of Tenormin [100 mg 'Atenolol' once daily] with or without chlorthalidone was carried out in 52 hypertensive patients with uncomplicated mild to moderately severe essential hypertension. A tablet count at the end of study enabled patient compliance to be judged. Of the 52 patients, 41 completed the study; 8 patients were lost to follow up and in 3 drug had to be withdrawn because of side effects. A statistically significant fall in systolic and diastolic blood pressure was observed in 15 patients taking Tenormin alone and in 26 when combined with Chlorthalidone. 84% patients showed fair or excellent compliance to therapy over this short period. 5 of 44 patients taking the drug suffered from side effects which included gastrointestinal disturbances [2], skin rash [1], retrosternal discomfort [1] and numbness of hands and feet [1]

Influence of beta-adrenoceptor antagonists on spontaneous rate and on force of contraction of isolated rabbit atria.

The influence of beta-adrenoceptor antagonists on the spontaneous rate and on force of contraction of the myocardium was studied independently on spontaneously beating right and electrically driven isolated left atria of rabbit. On spontaneous rate, practolol had sympathomimetic effect only, N-isopropylmethoxamine (IMA), had both sympathomimetic as well as depressant effects, whereas alprenolol, procinolol, bunolol and H 35/25 had depressant effects only in higher concentrations. The order of potency was procinolol greater than bunolol greater than alprenolol greater than H 35/25 greater than and IMA. On the contractions of isolated left atria, all beta-adrenoceptor antagonists produced concentration-dependent depressant effect. In relation to procinolol, these agents were 5-125 times less potent for depressing the contractions of left atria by 15% and the order of beta-potency was procinolol greater than alprenolol greater than bunolol = H 35/25 greater than IMA greater than and practolol. The present results indicate that the depressant effects of beta-adrenoceptor antagonists on spontaneous rate of right atria and on contraction of isolated left atria are not related to each other.