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.

Randomized, double-blind, placebo-controlled study of the analgesic effect of intraoperative esmolol for laparoscopic gastroplasty

Abstract Purpose To evaluate the analgesic effect of esmolol in patients submitted to laparoscopic gastroplasty. Methods Forty patients aged between 18 and 50 years with American Society of Anesthesiologists (ASA) physical status scores of II and III who underwent gastric bypass were allocated to two groups. Group 1 patients received a 0.5-mg/kg bolus of esmolol in 30 mL of saline before induction of anesthesia, followed by an infusion at 15 µg/kg/min until the end of surgery. Group 2 patients received 30 mL of saline as a bolus and then an infusion of saline. Anesthesia included fentanyl (3 µg/kg), propofol (2-4 mg/kg), rocuronium (0.6 mg/kg), and 2% sevoflurane, with remifentanil if necessary. The following parameters were evaluated: pain intensity over 24h, remifentanil consumption, the first analgesic request, morphine consumption, and side effects. Results Pain intensity was lower in the esmolol group except at T0 (after extubation) and 12h postoperatively. Remifentanil supplementation, recovery time, and postoperative morphine supplementation were lower in the esmolol group. No differences in the time to the first analgesic request or side effects were found between the groups. Conclusion Intraoperative esmolol promotes reductions in pain intensity and the need for analgesic supplementation without adverse effects, thus representing an effective drug for multimodal analgesia in gastroplasty.

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3±2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8±1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9±2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

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.

The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy

OBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.

Validation of a decision-making strategy for systolic anterior motion following mitral valve repair.

Low cardiac output syndrome and hypotension are dreadful consequences of systolic anterior motion (SAM) after a mitral valve (MV) repair. The management of SAM in the operating room remains controversial. We validate a recently suggested two-step management method and classification of this complication. This was a teaching hospital-based observational study. We validated a novel two-step conservative management method, consisting in intravascular volume expansion and discontinuation of inotropic drugs (step 1), and increasing the afterload by ascending aorta manual compression while administering esmolol e.v. (step 2). We also validate a novel classification of SAM: easy-to-revert (responding to step 1), difficult-to-revert (responding to step 2), or persistent. Fifty patients had an easy-to-revert while 26 had a difficult-to-revert SAM; 4 patients had a persistent condition (promptly diagnosed through our decisional algorithm) and underwent an immediate second pump run to repeat the mitral repair surgery. We confirmed that SAM after a repair of a degenerative MV is common and validated a simple two-step conservative management method that allows to clearly identify those few patients who require immediate surgical revision.

Efficacy of esmolol administration at different time intervals in attenuating hemodynamic response to tracheal intubation.

Background: Laryngoscopy and endotracheal intubation are known to cause increase in both arterial blood pressure and heart rate. Several strategies have been evolved to blunt the haemodynamic response to tracheal intubation but each method has its own advantages and disadvantages. Esmolol, a cardio selective Beta -1 blocking drug, can alleviate some of these problems. Esmolol, when administered parenterally, exhibits rapid onset and a short duration of action due to its rapid clearance by red blood cell esterases. Hence we conducted the present study to evaluate the efficacy and optimum time of single bolus esmolol administration in attenuating hypertensive- tachycardiac response to laryngoscopy and tracheal intubation. Materials and Methods: The randomized double blind prospective study was conducted in 60 patients, in the age group of 20-40 years, of both sexes, belonging to American Society of Anaesthesiologists (ASA) physical status class I or II and scheduled for elective surgery requiring endotracheal intubation and general anaesthesia. The efficacy and optimum time of single bolus esmolol administration in attenuating hypertensive - tachycardiac response to laryngoscopy and tracheal intubation was evaluated. Patients in group I (n=20) received bolus administration of injection esmolol 1.5 mg/kg intravenously (iv) 90 seconds before intubation; in group II (n=20) three minutes before intubation and in group III (n=20) six minutes before intubation. Results: There was no clinical and statistically significant variation in heart rate in group I and II at different time intervals of the study period but in group III heart rate increased significantly one minute after tracheal intubation. (P<0.05) One minute after intubation, the increase in systolic, diastolic and mean blood pressure and rate pressure product was statistically significant in group I (P<0.01) and group III. (P<0.05) However, in group II increase in systolic blood pressure and rate pressure product was statistically not significant. (P>0.05) Conclusion: To conclude, single intravenous bolus dose of esmolol (1.5 mg/kg) is safe and more effective in attenuating haemodynamic response to laryngoscopy and tracheal intubation when administered three minutes prior to intubation.

Substituição do carvedilol pelo propranolol em pacientes com insuficiência cardíaca / Replacement of carvedilol for propranolol in patients with heart failure

FUNDAMENTO: Grandes estudos clínicos empregando os betabloqueadores carvedilol, metoprolol, bisoprolol e nebivolol, demonstraram melhora da sobrevida e dos sintomas em pacientes com insuficiência cardíaca. Apesar da falta de evidências científicas, é plausível que o efeito benéfico seja extensível a outros betabloqueadores. OBJETIVO: Avaliar em pacientes com insuficiência cardíaca o impacto da substituição do carvedilol por propranolol sobre a função ventricular esquerda, capacidade funcional, qualidade de vida, níveis pressóricos e controle autonômico cardíaco. MÉTODOS: Vinte e nove pacientes com terapêutica medicamentosa otimizada incluindo doses máximas toleradas de carvedilol foram divididos em dois grupos: substituição de carvedilol por propranolol (n = 15) e manutenção de carvedilol (n = 14). Na condição basal, e após 6 meses, foram realizadas avaliações clínica e laboratorial com: ventriculografia nuclear, ecocardiografia, questionário de Minnesota, teste de caminhada, MAPA e Holter. RESULTADOS: As características laboratoriais e demográficas foram similares nos dois grupos na avaliação inicial. Ajuste individualizado da dose do propranolol garantiu grau semelhante de betabloqueio avaliado pela frequência cardíaca em repouso e reserva cronotrópica. A dose média de propranolol usada foi 109 ± 43 mg/dia. Apenas um paciente apresentou intolerância ao propranolol com retorno do carvedilol. Foi registrado um óbito no grupo propranolol. A fração de ejeção apresentou aumento significativo no grupo propranolol. As demais variáveis cardiovasculares não sofreram modificações significativas após troca do betabloqueador. CONCLUSÃO: Nossos resultados indicam que a substituição do carvedilol por propranolol em pacientes com insuficiência cardíaca não está associada à deterioração da fração de ejeção, da capacidade funcional, da qualidade de vida e das variáveis cardiovasculares de controle pressórico e autonômico.

BACKGROUND: Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers. OBJECTIVE: To evaluate the impact of the replacement of carvedilol for propranolol on left ventricular function, functional capacity, quality of life, pressure levels, and cardiac autonomic control in patients with heart failure. METHODS: Twenty nine patients receiving optimized drug therapy including maximum tolerated doses of carvedilol were divided into two groups: replacement of carvedilol for propranolol (n = 15) and continued carvedilol (n = 14). At baseline and 6 months later, clinical and laboratorial assessments were carried out with radionuclide ventriculography, echocardiography, Minnesota questionnaire, walk test, APBM and Holter monitoring. RESULTS: The clinical and demographic characteristics were similar in the two groups at baseline. Individualized propranolol dose adjustment ensured a similar degree of beta-blockade, as assessed by resting heart rate and chronotropic reserve. The mean propranolol dose used was 109 ± 43 mg/day. Only one patient presented with intolerance to propranolol, thus carvedilol was reintroduced. One death was recorded in group propranolol. Ejection fraction significantly increased in the propranolol group. No significant change was observed in the other cardiovascular variables after betablocker replacement. CONCLUSION: Our results indicate that replacement of carvedilol for propranolol in patients with heart failure is not associated with deterioration of the ejection fraction, functional capacity, quality of life, and other cardiovascular variables related to autonomic and blood pressure control., PP.0-0).

FUNDAMENTO: Grandes estudios clínicos empleando los betabloqueantes carvedilol, metoprolol, bisoprolol y nebivolol, demostraron mejora de la sobrevida y de los síntomas en pacientes con insuficiencia cardíaca. A pesar de la falta de evidencias científicas, es plausible que el efecto benéfico sea extensible a otros betabloqueantes. OBJETIVO: Evaluar en pacientes con insuficiencia cardíaca el impacto de la sustitución del carvedilol por propranolol sobre la función ventricular izquierda, capacidad funcional, calidad de vida, niveles presóricos y control autonómico cardíaco. MÉTODOS: Veintinueve pacientes con terapéutica medicamentosa optimizada incluyendo dosis máximas toleradas de carvedilol fueron divididos en dos grupos: sustitución de carvedilol por propranolol (n=15) y manutención de carvedilol (n=14). En la condición basal, y después de 6 meses, fueron realizadas evaluaciones clínica y de laboratorio con: ventriculografía nuclear, ecocardiografía, cuestionario de Minnesota, test de caminata, MAPA y Holter. RESULTADOS: Las características de laboratorio y demográficas fueron similares en los dos grupos en la evaluación inicial. Un ajuste individualizado de la dosis de propranolol garantizó grado semejante de betabloqueo evaluado por la frecuencia cardíaca en reposo y reserva cronotrópica. La dosis media de propranolol usada fue 109 1 43 mg/día. Apenas un paciente presentó intolerancia al propranolol con retorno al carvedilol. Fue registrado un óbito no grupo propranolol. La fracción de eyección presentó aumento significativo en el grupo propranolol. Las demás variables cardiovasculares no sufrieron modificaciones significativas después del cambio de betabloqueante. CONCLUSIÓN: Nuestros resultados indican que la sustitución del carvedilol por propranolol en pacientes con insuficiencia cardíaca no está asociada al deterioro de la fracción de eyección, de la capacidad funcional, de la calidad de vida y de las variables cardiovasculares de control presórico y autonómico

Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG / Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy

FUNDAMENTO: Alterações autonômicas na insuficiência cardíaca estão associadas a um aumento da morbimortalidade. Vários métodos não invasivos têm sido empregados para avaliar a função simpática, incluindo a imagem cardíaca com 123I-MIBG. OBJETIVO: Avaliar a atividade simpática cardíaca, por meio da cintilografia com 123I-MIBG, antes e após três meses de terapia com carvedilol em pacientes com insuficiência cardíaca com fração de ejeção do VE <45 por cento (FEVE). MÉTODOS: Foram recrutados para o estudo 16 pacientes, com idade média de 56,3 ± 12,6 anos (11 do sexo masculino), fração de ejeção média de 28 por cento ± 8 por cento e sem uso prévio de betabloqueadores. Realizaram-se imagens da inervação cardíaca com 123I-MIBG, determinando os níveis séricos de catecolaminas (epinefrina, dopamina e norepinefrina), e empreendeu-se a ventriculografia radionuclídica antes e após o uso de carvedilol por três meses. RESULTADOS: Houve melhora da classe funcional dos pacientes: antes do tratamento, metade se encontrava em CF II (50 por cento) e metade em CF III. Após 3 meses, 7 pacientes encontravam-se em CF I (43,8 por cento) e 9 em CF II (56,2 por cento), (p = 0,0001). A FEVE média avaliada pela ventriculografia radionuclídica aumentou de 29 por cento para 33 por cento (p = 0,017). Não houve variação significativa da atividade adrenérgica cardíaca avaliada pelo 123I-MIBG (imagem precoce, tardia e taxa de washout). Não foi observada variação significativa nas dosagens das catecolaminas. CONCLUSÃO: O tratamento em curto prazo com carvedilol promoveu a melhora clínica e da FEVE. Entretanto, não foi associado à melhora da atividade adrenérgica cardíaca pela cintilografia com 123I-MIBG, bem como da dosagem das catecolaminas circulantes.

BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45 percent. PATIENTS AND METHODS: Sixteen patients, aged 56.3 ± 12.6 years (11 males), with a mean LVEF of 28 percent ± 8 percent and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50 percent of the patients were FC II and 50 percent were FC III. After 3 months, 7 patients were FC I (43.8 percent) and 9 were FC II (56.2 percent), (p = 0.0001). The mean LVEF assessed by RIV increased from 29 percent to 33 percent (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Existe evidência para tratar insuficiência cardíaca baseada na raça ou etnia? / Is there evidence to treat heart failure based on race or ethnicity?

OBJETIVO: Avaliar se existe evidência que apóie diferentes intervenções para tratar insuficiência cardíaca baseada na raça ou etnia. MÉTODOS: Revisão sistemática de ensaios clínicos randomizados que permitiram comparar negros e brancos com insuficiência cardíaca sistólica crônica quanto à eficácia de inibidores da enzima conversora da angiotensina (ECA), betabloqueadores e combinação hidralazina/nitrato na redução dos riscos de morte e hospitalização. A pesquisa foi baseada em artigos publicados entre 1980 e dezembro de 2006, citados no Medline ou Lilacs. RESULTADOS: Três estudos preencheram os critérios da revisão. No SOLVD, enalapril foi eficaz em reduzir similarmente o risco de morte ou hospitalização em brancos (redução relativa do risco(RRR)=18 por cento) e negros (RRR= 17 por cento). No US Carvedilol, carvediol foi também associado a importante redução do risco de morte ou hospitalização tanto em brancos (RRR=49 por cento) quanto em negros (RRR=43 por cento). No V-HeFT II, enalapril foi superior a hidralazina/nitrato em reduzir o risco de morte apenas em brancos. CONCLUSÃO: De acordo com os dados, inibidores da ECA e betabloqueadores devem ser considerados os medicamentos básicos para melhorar o prognóstico da insuficiência cardíaca tanto em negros quanto em brancos. O estudo A-HeFT não foi incluído na revisão por ser restrito a negros; contudo deve ser visto como evidência que a combinação hidralazina e nitrato é eficaz em melhorar a sobrevida de pacientes com insuficiência cardíaca avançada. Os dados apóiam o desenvolvimento de um ensaio clinico especialmente desenhado para avaliar se a combinação hidralazina/nitrato é também eficaz em pacientes com insuficiência cardíaca avançada não classificados como negros.

OBJECTIVE: To assess if there is evidence to support different interventions for treatment of heart failure based upon race/ethnicity. METHODS: Systematic review of randomized clinical trials permitted comparisons between blacks and whites with systolic heart failure concerning the efficacy of angiotensin converting enzyme (ACE) inhibitors, beta blockers and a combination of hydralazine/ nitrate to reduce the risks of death and hospitalization. The literature search was based on articles published between 1980 and December 2006 cited in MEDLINE or LILACS. RESULTS: Three studies fulfilled the criteria of the reiew. In SOLVD, enalapril was efficient in reducing the risks of death or hospitalization similarly in whites (relative risk reduction (RRR) =18 percent) and blacks (RRR=17 percent). In US Carvedilol, carvediol was also associated with significant reduction in the risk of death or hospitalization both in whites (RRR=49 percent) and blacks (RRR=43 percent). In V-HeFT II, enalapril was superior to the combination hydralazine with nitrate in reducing the death risk only in whites. CONCLUSION: According to the data ACE inhibitors and beta blockers should be considered as the essential drugs to improve the prognosis of heart failure both in blacks and whites. The A-HeFT study was not included in the review because it was restricted to blacks; however, it should be viewed as evidence that the combination hydralazine/nitrate is beneficial to improve survival in patients with advanced heart failure. Data support development of a clinical trial especially designed to assess if the combination hydralazine/nitrate is also efficient in patients not classified as blacks, with advanced heart failure.

Effect of exercise training and carvedilol treatment on cardiac function and structure in mice with sympathetic hyperactivity-induced heart failure

The present investigation was undertaken to study the effect of â-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (alpha2A/alpha2CArKO). alpha2A/alpha2CArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and alpha2A/alpha2CArKO mice. At 5 months of age, all alpha2A/alpha2CArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, alpha2A/ alpha2CArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in alpha2A/alpha2CArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while beta-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wild-type control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in alpha2A/alpha2CArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise...

Heart rate dynamics during a treadmill cardiopulmonary exercise test in optimized beta-blocked heart failure patients

BACKGROUND: Calculating the maximum heart rate for age is one method to characterize the maximum effort of an individual. Although this method is commonly used, little is known about heart rate dynamics in optimized beta-blocked heart failure patients. AIM: The aim of this study was to evaluate heart rate dynamics (basal, peak and percent heart rate increase) in optimized beta-blocked heart failure patients compared to sedentary, normal individuals (controls) during a treadmill cardiopulmonary exercise test. METHODS: Twenty-five heart failure patients (49±11 years, 76 percent male), with an average LVEF of 30±7 percent, and fourteen controls were included in the study. Patients with atrial fibrillation, a pacemaker or noncardiovascular functional limitations or whose drug therapy was not optimized were excluded. Optimization was considered to be 50 mg/day or more of carvedilol, with a basal heart rate between 50 to 60 bpm that was maintained for 3 months. RESULTS: Basal heart rate was lower in heart failure patients (57±3 bpm) compared to controls (89±14 bpm; p<0.0001). Similarly, the peak heart rate ( percent maximum predicted for age) was lower in HF patients (65.4±11.1 percent) compared to controls (98.6±2.2; p<0.0001). Maximum respiratory exchange ratio did not differ between the groups (1.2±0.5 for controls and 1.15±1 for heart failure patients; p=0.42). All controls reached the maximum heart rate for their age, while no patients in the heart failure group reached the maximum. Moreover, the percent increase of heart rate from rest to peak exercise between heart failure (48±9 percent) and control (53±8 percent) was not different (p=0.157). CONCLUSION: No patient in the heart failure group reached the maximum heart rate for their age during a treadmill cardiopulmonary exercise test, despite the fact that the percentage increase of heart rate was similar to sedentary normal subjects. A heart rate increase in optimized beta-blocked...

Beta blockers for congestive heart failure.

The prognosis remains poor for many patients with congestive heart failure, despite maximal medical treatment with ACE inhibitor, diuretics and digitalis. In heart failure, activation of sympathetic nervous system has been described as one of the most important pathophysiologic abnormalities in patients with congestive heart failure and as one of the most important mechanisms that may be responsible for progression of heart failure. The use of beta blockers which may inhibit sympathetic activity, might reduce the risk of disease progression in heart failure, improve symptoms and increase survival. Several large clinical trials with metoprolol, carvedilol and bisoprolol have shown that long term use of these agents can improve left ventricular function and symptoms of CHF, it may also reduce hospital readmission and decrease mortality. Current guidelines recommend the use of beta blocker in mild, moderate and severe CHF, in the absence of contraindications or tolerance in combination with ACE inhibitor and diuretics. Beta blocker should be initiated in patients after maximal medical therapy with diuretics, ACE inhibitor and digitalis and patients already stabilized and in compensated conditions. Beta blocker should be started in low doses and require slow titration over weeks or months before patients can attain maintenance doses.

Could garlic be an useful adjuvant therapy in adriamycin heart failure?

50 year old suffering from breast carcinoma, treated with adriamycin developed heart failure with 22.82% ejection fraction. Added garlic pearl to routine anti-failure measures for 9 months to achieve 51.6% ejection fraction.

Effect of esmolol on oxidant status and antioxidant activity in acute myocardial infarction.

AIMS AND OBJECTIVES: The role of oxygen free radicals in reperfusion injury to the heart in myocardial infarction (MI) has been postulated. In this study, the clinical and antioxidant effects of esmolol, an ultra-short acting beta blocker in patients of acute MI was studied. MATERIAL AND METHODS: This was a randomized, double-blind, controlled, prospective study. Total 30 patients with acute MI were included. All patients were thrombolysed with streptokinase. Fifteen of these patients were randomly selected to receive esmolol while other 15 patients served as controls. The parameters compared at 0, 2 and 24 hours between the esmolol group and the controls were--malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX). RESULTS: Patients with MI had 5.16 times higher MDA level at 0 hours (20.34 +/- 6.12 nmol/ml vs. 3.94 +/- 0.70 nmol/ml, p < 0.0001) than MDA level in normal healthy population. At 2 hours, patients with MI had 5.71 times higher MDA level compared to normal healthy population (22.51 +/- 5.51 nmol/ml vs. 3.94 +/- 0.70 nmol/ml, p < 0.0001). A statistically significant difference in MDA levels at 2 and 24 hours was observed in MI patients given esmolol (mean change 2.06 +/- 5.39 nmol/ml vs. -4.47 +/- 6.93 nmol/ml, p = 0.009). Esmolol infusion also caused significant difference in GPX level at 2 hours compared to controls (23.79 + 14.68 U/gm Hb vs 38.3 +/- 8.95 U/gm Hb, p = 0.003). CONCLUSION: Free radical levels are raised in patients with MI which may contribute to reperfusion injury. The antioxidant action of esmolol was clearly observed by significant difference in MDA level and GPX sparing effect. Large scale clinical trials may establish conclusively role of beta blockers as antioxidants as adjuvant to thrombolytic therapy in MI.

Long QT syndrome manifesting as pulseless epilepsy.

A-10-year-old child admitted with repeated seizures due to the long QT syndrome is described. The cardiac origin of the epilepsy was suggested by the fact that during the episode of convulsions his peripheral pulses were not palpable.