Soil Microbiological Attributes Under Ecological Restoration Technologies in Subtropical Forest

Abstract To accelerate the recovery of degraded environments, it is necessary to use ecological restoration techniques, which require validation according to the ecosystem conditions where are implemented. This work aimed to evaluate soil microbiological attributes under different ecological restoration technologies in a subtropical forest. The study was conducted at UTFPR-DV, southwest of Paraná, in an ecotone between Mixed Ombrophilous Forest and Semideciduous Seasonal Forest and on an Oxisol. In December 2010, a tillage area of at least 17 years old was isolated and the passive restoration, tree planting and nucleation treatments were installed in 40x54 m plots and four replications. In November 2018 the soil was sampled in these plots and in a native forest area as a reference. There were calculated soil organic carbon content (OCC) and microbiological attributes such as microbial biomass N and C (NMIC and CMIC), basal respiration, fungal spore content and the metabolic (qCO2) and microbial quotient (MICq). It can be concluded that nucleation technology can restore soil microbiological attributes but has not yet reached the conditions of a natural environment. Passive restoration is not a good technology for restoring soil microbiological attributes. The higher contents of CMIC, NMIC, OCC, MICq and fungal spores in the soil under native forest compared to ecological restoration technologies indicate that eight years of adoption of these techniques have not yet been enough to fully recover soil microbiological activity.

Acupuncture and pharmacopuncture are as effective as morphine or carprofen for postoperative analgesia in bitches undergoing ovariohysterectomy

ABSTRACT PURPOSE : To investigate the analgesic effect of acupuncture (AP) or micro-dose pharmacopuncture (PA), using carprofen or morphine, in bitches undergoing ovariohysterectomy (OHE). METHODS: Thirty five dogs were randomly assigned to five groups after sedation with acepromazine IM: AP, 0.5 mg.kg-1 of morphine subcutaneously (SC), 4 mg.kg-1 of carprofen SC, and PA with 0.05 mg.kg-1 of morphine or 0.4 mg.kg-1 of carprofen. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed after OHE by a blind observer for 24h, by dynamic visual analogue scale (DIVAS), Glasgow (CMPS-SF), Melbourne (UMPS) and Colorado University pain scale (CSU). Animals reaching 33% of the UMPS score received rescue analgesia with morphine IM. Non parametric data were analysed by Kruskal-Wallis or Friedman tests where applicable, followed by Dunn´s test. Parametric data were analysed by two way ANOVA, followed by Tukey test. RESULTS: There were no differences among groups in number of rescue analgesia. Except for the DIVAS score where animals treated with morphine had the lowest score compared with AP and carprofen, at 1h after surgery, there were no other differences among groups. CONCLUSION: Acupuncture or pharmacopuncture were equally effective as morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy.

Carbazole degradation in the soil microcosm by tropical bacterial strains

In a previous study, three bacterial strains isolated from tropical hydrocarbon-contaminated soils and phylogenetically identified as Achromobacter sp. strain SL1, Pseudomonas sp. strain SL4 and Microbacterium esteraromaticum strain SL6 displayed angular dioxygenation and mineralization of carbazole in batch cultures. In this study, the ability of these isolates to survive and enhance carbazole degradation in soil were tested in field-moist microcosms. Strain SL4 had the highest survival rate (1.8 x 107 cfu/g) after 30 days of incubation in sterilized soil, while there was a decrease in population density in native (unsterilized) soil when compared with the initial population. Gas chromatographic analysis after 30 days of incubation showed that in sterilized soil amended with carbazole (100 mg/kg), 66.96, 82.15 and 68.54% were degraded by strains SL1, SL4 and SL6, respectively, with rates of degradation of 0.093, 0.114 and 0.095 mg kg−1 h−1. The combination of the three isolates as inoculum in sterilized soil degraded 87.13% carbazole at a rate of 0.121 mg kg−1 h−1. In native soil amended with carbazole (100 mg/kg), 91.64, 87.29 and 89.13% were degraded by strains SL1, SL4 and SL6 after 30 days of incubation, with rates of degradation of 0.127, 0.121 and 0.124 mg kg−1 h−1, respectively. This study successfully established the survivability (> 106 cfu/g detected after 30 days) and carbazole-degrading ability of these bacterial strains in soil, and highlights the potential of these isolates as seed for the bioremediation of carbazole-impacted environments.

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.

Acurácia na inferência de diagnósticos de enfermagem de pacientes com insuficiência cardíaca / La precisión en inferencia de diagnóstico de enfermería en pacientes con insuficiencia cardíaca / Accuracy in inference of nursing diagnoses in heart failure patients

RESUMOInsuficiência cardíaca (IC) é causa frequente de internação exigindo do enfermeiro precisão na conduta clínica e adequado julgamento dos diagnósticos de enfermagem.Objetivo:verificar acurácia na determinação dos diagnósticos de enfermagem fadiga, intolerância à atividade e débito cardíaco diminuído em paciente com IC hospitalizados.Método:estudo descritivo aplicado aos enfermeiros experientes em diagnósticos de enfermagem NANDA-I e/ou IC. Avaliação da acurácia foi realizada a partir do cálculo das medidas: eficácia (E), falso negativo (FN), falso positivo (FP) e tendência (T). Foram aptos os enfermeiros com inspeção aceitável para dois diagnósticos.Resultados:o diagnóstico de enfermagem fadiga foi o mais erroneamente identificado pelos enfermeiros avaliadores.Discussão:a busca pelo aperfeiçoamento da acurácia diagnóstica reafirma a necessidade de treinamento contínuo e específico para a melhora da capacidade diagnosticadora do enfermeiro.Conclusão:o treinamento permitiu o exercício do raciocínio clínico e melhor acurácia dos enfermeiros.

RESUMENInsuficiencia cardíaca (IC) es causa frecuente de ingresos hospitalarios exigindo del enfermero precisión en la conducta clínica y adecuado juzgamiento de los diagnósticos de enfermería.Objetivo:verificar la precisión en la determinación de los diagnósticos de enfermería fatiga, disminuición del gasto cardíaco e intolerancia a la actividad en pacientes con IC ingresos en hospitales.Método:estudio observacional, con enfermeros docentes y experientes en diagnósticos de enfermería NANDA-I y/o IC. Evaluación y precisión fueron realizadas por através del cálculo: eficacia (E), falso negativo (FN), falso positivo (FP) y tendecia (T). Fueron aptos los enfermeros con inspección aceptable para dos diagnósticos.Resultados:el diagnóstico de enfermería fatiga fue identificado erróneamente como por evaluadores enfermeras.Discusión:la búsqueda de la mejora de la precisión diagnóstica reafirma la necesidad de una formación continua y específica a la mejora de la capacidad del diagnosticador enfermera.Conclusión:la capacitación permitió el ejercicio del raciocínio y mejor precisión de los enfermeros.

ABSTRACTHeart failure (HF) is a common cause of hospitalization and requires accuracy in clinical judgment and appropriate nursing diagnoses.Objective:to determine the accuracy of nursing diagnoses of fatigue, intolerance to activity and decreased cardiac output in hospitalized HF patients.Method:descriptive study applied to nurses with experience in NANDA-I and/or HF nursing diagnoses. Evaluation and accuracy were determined by calculating effi cacy (E), false negative (FN), false positive (FP) and trend (T) measures. Nurses who showed acceptable inspection for two diagnoses were selected.Results:the nursing diagnosis of fatigue was the most commonly mistaken diagnosis identifi ed by the nursing evaluators.Discussion:the search for improving diagnostic accuracy reaffi rms the need for continuous and specifi c training to improve the diagnosis capability of nurses.Conclusion:the training allowed the exercise of clinical judgment and better accuracy of nurses.

Validación del método m­hidroxibifenilo para la cuantificación de ácido urónico en polisacáridos purificados de Streptococcus pneumoniae / Validation of the m-hydroxibiphenil method for the quantitation of uronic acid in purified Streptococcus pneumoniae polysaccharides

Introducción: la complejidad y diversidad estructural de los polisacáridos capsulares de Streptococcus pneumoniae hace que la metodología analítica necesaria para la caracterización y control de calidad sea engorrosa. El método colorimétrico m‒hidroxibifenil desarrollado por Blumenkrantz y Asboe‒Hansen en el año 1973, permite contrarrestar las desventajas del método propuesto en la Farmacopea Europea 6ta Edición, 2011. Objetivo: validar el método m‒hidroxibifenilo para cuantificar ácido urónico en polisacáridos purificados de streptococcus pneumoniae. Métodos: se determinó el tiempo de vigencia de la solución de tetraborato de sodio responsable de generar la respuesta analítica y se seleccionó una metodología para la cuantificación de ácido urónico por el método del m‒hidroxibifenilo se emplea una solución estándar de ácido galacturónico a 1 mg/mL. Se realizó una evaluación de los parámetros de validación: linealidad, exactitud, precisión, rango y especificidad, según exigencias actuales. Además se comparó con el método del carbazol descrito en la Farmacopea Europea 6ta Edición, 2011 para la cuantificación de ácido urónico. Resultados: se demostró que el tiempo de vida útil de la solución de tetraborato de sodio fue de 24 h. El método del m‒hidroxibifenilo fue específico, lineal, exacto y preciso en el rango de 2‒20 µg/mL porque se cumplieron satisfactoriamente los criterios de aceptación establecidos para cada uno de ellos. La comparación del método propuesto con el método normalizado reveló que no existieron diferencias estadísticamente significativas entre ambos(AU) Conclusión: el método colorimétrico del m‒hidroxibifenilo resultó válido para el control de calidad de las muestras de polisacárido purificado de Streptococcus pneumoniae, dando resultados comparables con el método recomendado en la Farmacopea Europea, 2011(AU)

Introduction: complexity and diversity in the structure of Streptococcus pneumoniae capsular makes the analytical methodology for characterization and quality control a troublesome aspect. The colorimetric m/hydroxibiphenil method devised by Blumenklrantz and Asboe-Hansen in 1973 allows reducing the disadvantages of the suggested method in the European Pharmacopea 6th edition, 2011. Objective: to validate the m-hydroxybiphenil method for quantitation of uronic acid in purified Streptococcus pneumonia polysaccharides. Methods: the length of validity of a sodium tetraborate solution, responsible for generating the analytical response, was estimated, and additionally, a methodology for quantitation of uronic acid by the m-hydroxybiphenil method was selected in which a standard galacturonic acid solution at 1mg/ml was used. The validation parameters were evaluated as follows: linearity, accuracy, precision, range and specificity, according to the present requirements. This method was compared with the carbazol method described in the European Pharmacopea 6th edition, 2011 for quantitation of uronic acid. Results: it was demonstrated that the useful lifetime of the sodium tetraborate solution was 24 hours. The m-hydroxybiphenil method was specific, linear, accurate and precise in the range of 2 to 20 ?g/mL because the set acceptance criteria were satisfactorily complied with for each of them. The comparison of the suggested method with the standardized method yielded that no statistically significant differences exist between them. Conclusions: the colorimetric m-hydroxybiphenil method proved to be valid for the quality control of purified Streptococcus pneumonia polysaccharide samples and the results are comparable to those of the recommended method in the European Pharmacopea, 2011(AU)

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.

High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

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.

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.

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.

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...

Protein tyrosine kinase inhibitors modify kainic acid-induced epileptiform activity and mossy fiber sprouting but do not protect against limbic cell death

Intrahippocampal administration of kainic acid (KA) induces synaptic release of neurotrophins, mainly brain-derived neurotrophic factor, which contributes to the acute neuronal excitation produced by the toxin. Two protein tyrosine kinase inhibitors, herbimycin A and K252a, were administered intracerebroventricularly, in a single dose, to attenuate neurotrophin signaling during the acute effects of KA, and their role in epileptogenesis was evaluated in adult, male Wistar rats weighing 250-300 g. The latency for the first Racine stage V seizure was 90 ± 8 min in saline controls (N = 4) which increased to 369 ± 71 and 322 ± 63 min in animals receiving herbimycin A (1.74 nmol, N = 4) and K252a (10 pmol, N = 4), respectively. Behavioral alterations were accompanied by diminished duration of EEG paroxysms in herbimycin A- and K252a-treated animals. Notwithstanding the reduction in seizure severity, cell death (60-90 percent of cell loss in KA-treated animals) in limbic regions was unchanged by herbimycin A and K252a. However, aberrant mossy fiber sprouting was significantly reduced in the ipsilateral dorsal hippocampus of K252a-treated animals. In this model of temporal lobe epilepsy, both protein kinase inhibitors diminished the acute epileptic activity triggered by KA and the ensuing morphological alterations in the dentate gyrus without diminishing cell loss. Our current data indicating that K252a, but not herbimycin, has an influence over KA-induced mossy fiber sprouting further suggest that protein tyrosine kinase receptors are not the only factors which control this plasticity. Further experiments are necessary to elucidate the exact signaling systems associated with this K252a effect.

Evaluación del efecto de carvedilol en niños con cardiomiopatía dilatada / Evaluation of the effect of carvedilol in children with dilated cardiomyopathy

OBJECTIVE: To evaluate the effect of carvedilol administrated during 8 months in children with heart failure secondary to dilated cardiomyopathy. METHODS: We initiated carvedilol in patients who, despite optimization of standard treatment, had persistent left ventricular ejection fraction < or = 40% and evaluated the systolic and diastolic left ventricular function before and after 4 and 8 months of treatment. RESULTS: 19 patients were included in the study, 10 women; median age: 6.7 years and 17 +/- 12.4 months after the diagnosis. The ejection fraction improved significantly from entry to eight months (median: 33.5 to 52.6%, p = 0.01) as did the shortening fraction (m: 14.8 to 25.8%, p = 0.01). The myocardial performance index abnormal in all 19 patients became normal in 5 at the end of study. In addition mitral Doppler flow which was altered in 9 improved in 3 and pulmonary venous flow abnormal in all patients improved in 13. Only 1 patient presented minimal adverse effects. CONCLUSIONS: Carvedilol added to standard therapy for dilated cardiomyopathy improves left ventricular function, is well tolerated, and has minimal adverse effects in childhood.

The relationship between heart rate reserve and oxygen uptake reserve in heart failure patients on optimized and non-optimized beta-blocker therapy

BACKGROUND: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients either on non-optimized or off beta-blocker therapy is known to be unreliable. The aim of this study was to evaluate the relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients receiving optimized and non-optimized beta-blocker treatment during a treadmill cardiopulmonary exercise test. METHODS: A total of 27 sedentary heart failure patients (86 percent male, 50±12 years) on optimized beta-blocker therapy with a left ventricle ejection fraction of 33±8 percent and 35 sedentary non-optimized heart failure patients (75 percent male, 47±10 years) with a left ventricle ejection fraction of 30±10 percent underwent the treadmill cardiopulmonary exercise test (Naughton protocol). Resting and peak effort values of both the percentage of oxygen consumption reserve and percentage of heart rate reserve were, by definition, 0 and 100, respectively. RESULTS: The heart rate slope for the non-optimized group was derived from the points 0.949±0.088 (0 intercept) and 1.055±0.128 (1 intercept), p<0.0001. The heart rate slope for the optimized group was derived from the points 1.026±0.108 (0 intercept) and 1.012±0.108 (1 intercept), p=0.47. Regression linear plots for the heart rate slope for each patient in the non-optimized and optimized groups revealed a slope of 0.986 (almost perfect) for the optimized group, but the regression analysis for the non-optimized group was 0.030 (far from perfect, which occurs at 1). CONCLUSION: The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in patients on optimized beta-blocker therapy was reliable, but this relationship was unreliable in non-optimized heart failure patients.