Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Rendimiento deportivo en la altura: Efecto del sildenafil / Sildenafil and exercise performance at altitude

La presión barométrica y la presión parcial de O2 disminuyen con la altura y la hipoxia hipobárica generada es la responsable de las enfermedades relacionadas con la altitud y del deterioro del rendimiento deportivo. Las adaptaciones fisiológicas a la altura son múltiples y contribuyen a la alteración de las diferentes cualidades atléticas. Se ha planteado que el deterioro del VO2 podría estar asociado a incrementos de la resistencia vascular pulmonar, así como a una alteración de la difusión pulmonar de óxido nítrico. La eficacia para el tratamiento de la hipertensión pulmonar demostrada por el sildenafil ha llevado a sugerir que su indicación para competencias en altura podría mejorar el rendimiento. Las investigaciones demuestran resultados diferentes según el nivel de altitud y los tiempos e intensidades del ejercicio. Algunos muestran mejoras del rendimiento, aunque no en todos los participantes. Existen condiciones individuales que podrían resultar en efectos mayores, menores o nulos. En esta presentación se analizan los efectos de la altura sobre la capacidad de esfuerzo, se muestran estudios, efectos colaterales eventuales y repercusiones del empleo de sildenafil para mejorar el rendimiento deportivo en altura. El médico deberá conocer en cada deportista los efectos colaterales individuales que podrían surgir y que influirían negativamente sobre la salud y el rendimiento.

Barometric pressure and partial oxygen pressure decrease with increasing altitude. Hypobaric hypoxia produced is responsible for altitude-related diseases and it can cause severe decrements in exercise performance. The physiological adaptations to the altitude are multiple and they contribute to alter different athletic qualities. The VO2 worsening could be associated to increased pulmonary vascular resistance and nitric oxide diffusion alteration. Performance impairments at altitude can also be accentuated by hypoxia-induced elevations in pulmonary arterial pressure. Clinical studies have demonstrated the beneficial effects of sildenafil on the treatment of pulmonary hypertension. These effects have led to suggest that its indication for competitions at altitude might improve athletic performance. The investigations demonstrate different results depending on the altitude level and times and intensities of exercise. Some studies show performance improvements, although not in all participants. Individual responses vary widely between different athletes. This presentation examines the effects of altitude on exercise capacity and shows studies about the use of sildenafil to improve sport performance. This text also discusses the possible side effects and implications for the use of sildenafil in athletes, indication that is not the basic one of the drug. The physicians must know in each athlete the individual sildenafil side effects that could arise and that would influence negatively on health and performance.

Six-minute walk test and respiratory muscle strength in patients with uncontrolled severe asthma: a pilot study / Teste de caminhada de seis minutos e força muscular respiratória em pacientes com asma grave não controlada: um estudo piloto

OBJECTIVE: To evaluate respiratory muscle strength and six-minute walk test (6MWT) variables in patients with uncontrolled severe asthma (UCSA). METHODS: This was a cross-sectional study involving UCSA patients followed at a university hospital. The patients underwent 6MWT, spirometry, and measurements of respiratory muscle strength, as well as completing the Asthma Control Test (ACT). The Mann-Whitney test was used in order to analyze 6MWT variables, whereas the Kruskal-Wallis test was used to determine whether there was an association between the use of oral corticosteroids and respiratory muscle strength. RESULTS: We included 25 patients. Mean FEV1 was 58.8 ± 21.8% of predicted, and mean ACT score was 14.0 ± 3.9 points. No significant difference was found between the median six-minute walk distance recorded for the UCSA patients and that predicted for healthy Brazilians (512 m and 534 m, respectively; p = 0.14). During the 6MWT, there was no significant drop in SpO2. Mean MIP and MEP were normal (72.9 ± 15.2% and 67.6 ± 22.2%, respectively). Comparing the patients treated with at least four courses of oral corticosteroids per year and those treated with three or fewer, we found no significant differences in MIP (p = 0.15) or MEP (p = 0.45). CONCLUSIONS: Our findings suggest that UCSA patients are similar to normal subjects in terms of 6MWT variables and respiratory muscle strength. The use of oral corticosteroids has no apparent impact on respiratory muscle strength. .

OBJETIVO: Avaliar a força muscular respiratória e variáveis obtidas no teste de caminhada de seis minutos (TC6) em pacientes com asma grave não controlada (AGNC). MÉTODOS: Estudo transversal, envolvendo pacientes com AGNC acompanhados em um hospital universitário. Os pacientes foram submetidos a TC6, espirometria e medidas da força muscular respiratória e responderam o Asthma Control Test (ACT, Teste de Controle da Asma). O teste de Mann-Whitney foi utilizado na análise das variáveis do TC6, e o teste de Kruskal-Wallis foi utilizado na verificação de uma possível associação do uso de corticoide oral com a força muscular respiratória. RESULTADOS: Foram incluídos 25 pacientes, com médias de VEF1 de 58,8 ± 21,8% do previsto e escore do ACT de 14,0 ± 3,9 pontos. Não houve diferença significativa entre a mediana da distância percorrida no TC6 dos pacientes com AGNC e aquela prevista para brasileiros saudáveis (512 m e 534 m, respectivamente; p = 0,14). Durante o TC6, não houve queda significativa da SpO2. As médias de PImáx e PEmáx foram normais (72,9 ± 15,2% e 67,6 ± 22,2%, respectivamente). Não houve diferenças significativas nas medidas de PImáx (p = 0,15) e PEmáx (p = 0,45) entre os pacientes que usavam ao menos quatro ciclos de corticoide oral por ano e os que o usavam por três ou menos ciclos por ano. CONCLUSÕES: Nossos achados sugerem que os pacientes com AGNC são semelhantes a indivíduos normais em termos das variáveis do TC6 e da força muscular respiratória. Não se observou um impacto do uso de corticoide oral na força muscular respiratória. .

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

The thyroid hormone receptor β-selective agonist GC-1 does not affect tolerance to exercise in hypothyroid rats

Objective Investigate the effect of GC-1 on tolerance to exercise in rats with experimental hypothyroidism. Materials and methods Hypothyroidism was induced with methimazole sodium and perchlorate treatment. Six groups with eight animals were studied: control group (C), hypothyroid group without treatment (HYPO); hypothyroidism treated with physiological doses of tetraiodothyronine (T4) or 10 times higher (10×T4); hypothyroidism treated with equal molar doses of GC-1 (GC-1) or 10 times higher (10×GC-1). After eight weeks, each animal underwent an exercise tolerance test by measuring the time (seconds), in which the rats were swimming with a load attached to their tails without being submerging for more than 10 sec. After the test, the animals were killed, and blood samples were collected for biochemical analysis, and the heart and soleus muscle were removed for weighing and morphometric analysis of the cardiomyocyte. Results Hypothyroidism significantly reduced tolerance to exercise and, treatment with GC-1 1× or T4 in physiological doses recover tolerance test to normal parameters. However, high doses of T4 also decreased tolerance to physical exercise. Conversely, ten times higher doses of GC-1 did not impair tolerance to exercise. Interestingly, hypothyroidism, treated or not with T4 in a physiological range, GC-1 or even high doses of GC-1 (10X) did not change cardiomyocyte diameters and relative weight of the soleus muscle. In contrast, higher doses of T4 significantly increased cardiomyocyte diameter and induced atrophy of the soleus muscle. Conclusion Unlike T4, GC-1 in high doses did not modify tolerance to physical exercise in the rats with hypothyroidism. .

No Synergic Effect of Sildenafil Administration on Exercise Capacity Improvement in a Fontan Patient with Regular Exercise Training.

In Fontan patients, reduced exercise capacity due to diminished cardiac output is a common finding with important prognostic implications. Beneficial effects have been shown for sildenafil treatment and regular exercise, but data comparing both strategies is scarce. We report on a female patient with Fontan circulation who underwent repeated cardiopulmonary exercise tests with either placebo or a single dose of 50mg sildenafil before and after 6months of supervised aerobic and resistance exercise. At baseline, V O2peak was 29.1ml/min/kg, and a marked increase to 32.8ml/min/kg was observed after administration of sildenafil. After the training period, V O2peak was 34.5ml/kg/min in the placebo test, and no further increase by sildenafil was possible (33.7ml/kg/min). Similar results were observed for exercise capacity at the ventilatory anaerobic threshold. In summary, this Fontan patient showed that regular exercise might use up and probably exceed the acute sildenafil effects on exercise capacity. Exercise should be considered as a primary treatment strategy within secondary prevention and rehabilitation after the Fontan procedure.

Can bronchodilators improve exercise tolerance in COPD patients without dynamic hyperinflation? / Os broncodilatadores podem melhorar a tolerância ao exercício na ausência de hiperinsuflação dinâmica em pacientes com DPOC?

OBJECTIVE: To investigate the modulatory effects that dynamic hyperinflation (DH), defined as a reduction in inspiratory capacity (IC), has on exercise tolerance after bronchodilator in patients with COPD. METHODS: An experimental, randomized study involving 30 COPD patients without severe hypoxemia. At baseline, the patients underwent clinical assessment, spirometry, and incremental cardiopulmonary exercise testing (CPET). On two subsequent visits, the patients were randomized to receive a combination of inhaled fenoterol/ipratropium or placebo. All patients then underwent spirometry and submaximal CPET at constant speed up to the limit of tolerance (Tlim). The patients who showed ΔIC(peak-rest) < 0 were considered to present with DH (DH+). RESULTS: In this sample, 21 patients (70%) had DH. The DH+ patients had higher airflow obstruction and lower Tlim than did the patients without DH (DH-). Despite equivalent improvement in FEV1 after bronchodilator, the DH- group showed higher ΔIC(bronchodilator-placebo) at rest in relation to the DH+ group (p < 0.05). However, this was not found in relation to ΔIC at peak exercise between DH+ and DH- groups (0.19 ± 0.17 L vs. 0.17 ± 0.15 L, p > 0.05). In addition, both groups showed similar improvements in Tlim after bronchodilator (median [interquartile range]: 22% [3-60%] vs. 10% [3-53%]; p > 0.05). CONCLUSIONS: Improvement in TLim was associated with an increase in IC at rest after bronchodilator in HD- patients with COPD. However, even without that improvement, COPD patients can present with greater exercise tolerance after bronchodilator provided that they develop DH during exercise. .

OBJETIVO: Investigar os efeitos moduladores da hiperinsuflação dinâmica (HD), definida pela redução da capacidade inspiratória (CI), na tolerância ao exercício após broncodilatador em pacientes com DPOC. MÉTODOS: Estudo experimental e randomizado com 30 pacientes com DPOC sem hipoxemia grave. Na visita inicial, os pacientes realizaram avaliação clínica, espirometria e teste de exercício cardiopulmonar (TECP) incremental. Em duas visitas subsequentes, os pacientes foram randomizados para receber uma combinação de fenoterol/ipratrópio ou placebo e, em seguida, realizaram espirometria e TECP com velocidade constante até o limite da tolerância (Tlim). Os pacientes com ΔCI(pico-repouso) < 0 foram considerados com HD (HD+). RESULTADOS: Nesta amostra, 21 pacientes (70%) apresentaram HD. Os pacientes HD+ apresentaram maior obstrução ao fluxo aéreo e menor Tlim do que os pacientes sem HD (HD-). Apesar de ganhos equivalentes de VEF1 após broncodilatador, o grupo HD- apresentou maior ΔCI(broncodilatador-placebo) em repouso em relação ao grupo HD+ (p < 0,05). Entretanto, isso não ocorreu com a ΔCI no pico do exercício entre os grupos HD+ e HD- (0,19 ± 0,17 L vs. 0,17 ± 0,15 L; p > 0,05). Similarmente, ambos os grupos apresentaram melhoras equivalentes do Tlim após broncodilatador (mediana [intervalo interquartílico]: 22% [3-60%] e 10% [3-53%]; p > 0,05). CONCLUSÕES: A melhora da CI em repouso após broncodilatador associou-se com ganho de tolerância ao esforço mesmo nos pacientes com DPOC que não apresentem HD. Por outro lado, pacientes sem melhora da CI em repouso ainda podem obter beneficio funcional com o broncodilatador desde que apresentem HD no exercício. .

Effects of intensive versus mild lipid lowering by statins in patients with ischemic congestive heart failure: Korean Pitavastatin Heart Failure (SAPHIRE) study

BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.

Evolução do status de performance, índice de massa corpórea e distância percorrida no teste de caminhada de seis minutos em pacientes com câncer de pulmão avançado submetidos à quimioterapia / Evolution of performance status, body mass index, and six-minute walk distance in advanced lung cancer patients undergoing chemotherapy

OBJETIVO: Avaliar o efeito da quimioterapia sobre a condição física de pacientes com câncer de pulmão avançado. MÉTODOS: Foram avaliados 50 pacientes com câncer de pulmão não pequenas células nos estágios IIIB e IV e com status de performance segundo a escala do Eastern Cooperative Oncology Group (ECOG) entre zero e dois. Todos receberam quimioterapia com as drogas paclitaxel e derivados da platina e foram avaliados em três momentos (pré-quimioterapia, pós-quimioterapia e seis meses após o início do tratamento), nos quais a escala ECOG, o índice de massa corpórea (IMC) e a Distância percorrida no Teste de Caminhada de Seis minutos (DTC6) foram avaliados. RESULTADOS: Dos 50 pacientes incluídos, 14 foram a óbito, 5 foram excluídos do estudo por apresentar piora do status de performance, e 31 concluíram o seguimento de seis meses. Não houve diferença estatisticamente significativa para o IMC (p = 1,00, pré-quimioterapia vs. pós-quimioterapia; e p = 0,218, pré-quimioterapia vs. seis meses após) ou para a DTC6 entre os momentos de avaliação. O status de performance melhorou, principalmente com o aumento do número de pacientes assintomáticos após seis meses de acompanhamento (p = 0,031). CONCLUSÕES: O uso de quimioterapia teve um efeito benéfico no status de performance dos pacientes. Não houve alterações no IMC ou na DTC6 durante o período do estudo, o que pode sugerir a manutenção da condição física dos pacientes.

OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. METHODS: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

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...

Capacidade inspiratória, limitação ao exercício, e preditores de gravidade e prognóstico, em doença pulmonar obstrutiva crônica / Inspiratory capacity, exercise limitation, markers of severity, and prognostic factors in chronic obstructive pulmonary disease

OBJETIVO: Correlacionar a capacidade inspiratória (CI), por cento do previsto, pós-broncodilatador (pós-BD), com outras variáveis indicativas de gravidade e prognóstico, na doença pulmonar obstrutiva crônica (DPOC). MÉTODOS: Oitenta pacientes estáveis com DPOC realizaram manobras de capacidade vital forçada, capacidade vital lenta, e teste de caminhada de 6 min, antes e após salbutamol spray (400 µg). Foram divididos em quatro grupos, segundo o volume expiratório forçado no primeiro segundo pós-BD. Diversas variáveis foram testadas, por análise univariada e multivariada, com a distância caminhada pós-BD, por cento do previsto. A CI pós-BD foi correlacionada com o estadiamento Global Initiative for Chronic Obstructive Lung Disease (GOLD) e o índice Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE). RESULTADOS: Por análise de regressão multivariada, a CI pós BD, por cento do previsto, (p = 0,001), o uso de oxigênio a longo prazo (p = 0,014), e o número de medicamentos usados (p = 0,044), mantiveram associação significativa com a distância caminhada, por cento do previsto. A CI < 70 por cento foi observada em 56 por cento dos pacientes em estágios GOLD 3 ou 4 comparado a 20 por cento em estágios GOLD 1 ou 2 ( p < 0,001). A CI < 70 por cento foi observada em 60 por cento dos pacientes com escore BODE 3 ou 4 vs. 33 por cento com BODE 1 ou 2 (p = 0,02). CONCLUSÃO: A CI, por cento do previsto, pós-BD é o melhor preditor funcional da distância caminhada, associando-se significativamente com o escore GOLD e o índice BODE. Por isso, propomos que a CI seja incluída na rotina de avaliação dos portadores de DPOC.

OBJECTIVE: To correlate the postbronchodilator (post-BD) inspiratory capacity (IC), percent of predicted, with other markers of severity and prognostic factors in chronic obstructive pulmonary disease (COPD). METHODS: Eighty stable patients with COPD performed forced vital capacity and slow vital capacity maneuvers, as well as the 6-min walk test, prior to and after receiving albuterol spray (400 µg). Patients were divided into four groups, based on post-BD forced expiratory volume in one second. Several variables were tested to establish correlations with the post-BD distance walked, using univariate and multivariate analysis. Post-BD IC was found to correlated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and with the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index. RESULTS: Multivariate regression analysis revealed that the distance walked, percent predicted, correlated significantly with the IC post-BD, percent predicted (p = 0.001), long-term oxygen use (p = 0.014), and number of medications used in the treatment (p = 0.044). IC < 70 percent was observed in 56 percent patients in GOLD stages 3 or 4 vs. 20 percent in GOLD 1 or 2 (p < 0.001). IC < 70 percent was observed in (60 percent) patients with BODE score 3 or 4 vs. (33 percent) BODE score 1 or 2 (p = 0.02). CONCLUSION: Post-BD IC percent predicted is the best functional predictor of distance walked and is significantly associated with GOLD staging and BODE index. Therefore, We propose that the inspiratory capacity should be added to the routine evaluation of the COPD patients.

Efeito da teofilina associada ao beta2-agonista inalatório de curta ou longa duração, em pacientes com doença pulmonar obstrutiva crônica estável: revisão sistemática / Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review

OBJETIVOS: Avaliar se o tratamento com teofilina associada ao beta2-agonista inalatório de curta ou longa duração é mais eficaz que o placebo e que o uso isolado de cada um dos fármacos, para os pacientes com doença pulmonar obstrutiva crônica estável. MÉTODOS: Realizou-se uma revisão sistemática com metanálise, sendo selecionados todos os ensaios clínicos aleatórios e duplo-cegos encontrados na literatura. RESULTADOS: Foram incluídos oito estudos. Teofilina associada ao beta2-agonista vs. placebo: houve melhora estatisticamente significante para o VEF1 (L), com média 0,27 (IC95 por cento 0,11 a 0,43); e para a dispnéia, com média -0,78 (IC95 por cento -1,26 a -0,29). Teofilina associada ao beta2-agonista vs. beta2-agonista isolado: nenhuma das metanálises realizadas detectou diferença entre os grupos. Teofilina associada ao beta2-agonista vs. teofilina isolada: houve melhora estatisticamente significante para a dispnéia, com média -0,19 (IC95 por cento -0,34 a -0,04). CONCLUSÕES: Em pacientes com doença pulmonar obstrutiva crônica estável: 1) teofilina associada ao beta2-agonista é mais eficaz que o placebo, em relação ao VEF1 e dispnéia; 2a) teofilina associada ao beta2-agonista é mais eficaz que a teofilina isolada, em relação à dispnéia; e 2b) teofilina associada ao beta2-agonista não é mais eficaz que o beta2-agonista isolado, para quaisquer das variáveis estudadas.

OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95 percentCI: 0.11 to 0.43) and mean dyspnea (-0.78; 95 percentCI: -1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with beta2-agonists and those obtained using beta2-agonists alone. When the administration of theophylline combined with beta2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95 percentCI: -0.34 to 0.04). CONCLUSION: In patients with stable chronic obstructive pulmonary disease, theophylline combined with beta2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with beta2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with beta2 agonists is no more efficacious, for any of the variables studied, than is the use of beta2-agonists in isolation.

Use of Tadalafil for Treating Pulmonary Arterial Hypertension Secondary to Chronic Obstructive Pulmonary Disease

Pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD) is incurable and it has an unpredictable survival rate. Two men who suffered from COPD presented with progressive dyspnea and edema, respectively. PAH, as estimated by the peak velocity of tricuspidal regurgitation, and the depressed myocardial performance index (MPI) of the right ventricle (RV) were noted on echocardiography. In addition to the baseline therapy for their depressed ventilatory function, we prescribed tadalafil 10 mg orally every other day for 2 weeks and then we doubled the dosage. They well tolerated the medication without any notable side effects. After 4 weeks of tadalafil treatment, the patients' pulmonary arterial pressure was decreased and the MPI of the RV was improved in both. The exercise capacity, as measured by the respiratory oxygen uptake, also improved from 10.9 mL/kg/min to 13.8 mL/kg/min in one patient. We report here on 2 patients with PAH secondary to COPD, and they showed notable improvement of their pulmonary hemodynamics and exercise capacity with the administration of tadalafil.

L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs

The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. Sixteen COPD patients (66 ± 7 years) were randomly assigned to L-carnitine (CG) or placebo group (PG) that received either L-carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory volume on first second was 38 ± 16 and 36 ± 12 percent, respectively). Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40 percent) at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05). Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 ± 14 vs 14 ± 5 cmH2O, and 87 ± 30 vs 34 ± 29 m, respectively; P < 0.05). Blood lactate concentration was significantly lower in CG than in PG (1.6 ± 0.7 vs 2.3 ± 0.7 mM, P < 0.05). The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Effect of garlic (Allium sativum) oil on exercise tolerance in patients with coronary artery disease.

The effect of six weeks garlic oil administration was observed on cardiac performance and exercise tolerance in 30 patients of coronary artery disease. After initial treadmill stress test, they were administered garlic oil in the dose of four capsules twice a day for 6 weeks and treadmill stress test was repeated. Garlic significantly (P<0.01) reduced heart rate at peak exercise and also significantly reduced the work load upon the heart resulting in better exercise tolerance (P<0.05) as compared to the initial test. It appears to be a good adaptogen to be utilized in patients with coronary artery disease.

An evaluation of salmeterol in the treatment of chronic obstructive pulmonary diseases.

BACKGROUND: Salmeterol has been shown a useful drug for the treatment of chronic obstructive pulmonary disease (COPD). However, its positioning in the current treatment of COPD remains to be defined. The present study was carried out to evaluate its role as an add-on drug to the current first-line drug, ipratropium. METHODS: A double-blind randomized, parallel group, placebo-controlled design was used in an outpatient setting. Thirty-three patients with moderate or severe COPD were included. After a run-in period of two weeks on 40 microg four-times-daily ipratropium and 400 microg twice-daily beclomethasone dipropionate, they were randomized into two groups to receive either salmeterol (50 microg twice daily) or placebo for eight weeks. The outcome parameters were: (i) spirometry, (ii) six-minute walking test, (iii) SF-36 health-related quality of life (HRQoL) questionnaire score, (iv) baseline dyspnoea index (BDI), (v) patient's self-assessment and (vi) supplemental use of salbutamol. RESULTS: The mean FEV1 and FVC increased significantly over the initial values in the salmeterol group but not in the placebo group. Salmeterol produced greater improvements in almost all the dimensions of HRQoL as well as in the BDI and the supplemental use of salbutamol was lower in this group. However, the six-minute walk distance was similar in the two groups. CONCLUSIONS: The present study shows that eight weeks treatment with salmeterol 50 microg twice-daily added to the existing regimen of ipratropium bromide and beclomethasone dipropionate provides greater symptomatic relief and improvement in lung function than placebo. This is accompanied by an improvement in the health-related quality of life.

L-carnitine moderately improves the exercise tolerance in chronic stable angina.

OBJECTIVES: To study the safety and efficacy (with reference to exercise ECG testing) of oral L-carnitine in chronic stable angina. METHODS: Forty-seven patients, 30 men and 17 women, aged 56 +/- 8 years, were randomized to receive L-carnitine (n = 28) or placebo (n = 19) in the dose of 2 g/day for 3 months. The adjuvant treatment was not changed during the study. Patients were evaluated by computerized stress test (CST) done at the beginning and end of the trial. The parameters assessed were exercise duration, time to onset of ST changes, total ST score at peak exercise, rate-pressure product at peak exercise, and time needed for the ST changes to recover to baseline. RESULTS: The two groups were comparable at the beginning of the study. There was no change in the CST parameters in the placebo group at the end of 3 months. In the L-carnitine group there was a statistically significant improvement in the exercise duration from 7.8 +/- 2.2 min to 8.6 +/- 1.8 min (p = 0.006) and in the time needed for the ST changes to revert to baseline from 7.2 +/- 3.9 min to 5.7 +/- 3.8 min (p = 0.019). No change was noted in the time to onset for ST depression, ST score and double product. There were no systemic adverse effects or coronary events in either group. CONCLUSION: Oral L-carnitine is safe and moderately improves the duration of exercise and time to recovery of ST changes in patients with chronic stable angina.

Exercise-induced ventricular arrhythmias in congestive heart failure and role of ACE inhibitors.

Ventricular arrhythmias are considered to be related to left ventricular (LV) dysfunction. ACE inhibitors though improve LV function their beneficial role on exercise-induced ventricular arrhythmias is not established. To study the effects of ACE inhibitors on exercise capacity vis-a-vis their role on exercise-induced ventricular arrhythmias, 25 patients of congestive heart failure (CHF) of various etiologies in NYHA Class II and III were subjected to a prospective randomised controlled trial. The control group comprising of 12 patients received conventional treatment (digitalis and diuretics) and the test group was given enalapril/captopril in addition as tolerated. They were followed up for 3 months. Exercise testing on treadmill and monitoring of clinical and biochemical parameters were done at the beginning and end of study in all cases. Ventricular arrhythmias observed during exercise and post-exercise for 10 minutes was analysed using Lown's grading for frequency and severity of ventricular arrhythmia. The mean exercise duration showed significant improvement on ACE inhibitor as compared to the control group (p < 0.05) however there was no significant change in the grades of arrhythmia. Serum electrolytes and other bio-chemical parameter were within normal range. It is concluded that effect of ACE inhibitor on improving functional capacity in CHF is independent of it's any effect on exercise-induced ventricular arrhythmias.

Beneficial effects of long-term metoprolol therapy on cardiac haemodynamics in patients with mitral stenosis in sinus rhythm--a randomised clinical trial.

We conducted a placebo controlled randomised clinical trial to evaluate the effects of 6 months therapy with metoprolol on resting and exercise haemodynamics in 31 patients with isolated mitral stenosis in sinus rhythm. Twenty six of them (placebo n = 13, metoprolol n = 13) completed the study protocol. Their mean age was 23.1 +/- 7.9 years and the mean mitral valve area was 0.93 +/- 0.25 cm2. The dose of metoprolol ranged between 50-100 mg per day. The primary outcome variables for the study were the resting and exercise mean pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) and the secondary outcome variables consisted of resting and exercise heart rate, mean pulmonary artery pressure (PAP), mean pulmonary vascular resistance (PVR) and clinical improvement on visual analog scale. These outcome variables were assessed blindly. The resting and exercise mean PCWP (mmHg) increased by 9.1 +/- 3.1 and 16.4 +/- 6.4 on placebo and 2.5 +/- 2.1 and -4.6 +/- 2.3 on metoprolol after 6 months therapy. These differences were statistically significant (p < 0.01). The resting and exercise CI (liters/min/m2) decreased by 0.2 +/- 0.1 and 0.1 +/- 0.1 on placebo and 0.3 +/- 0.5 and 0.3 +/- 1.0 on metoprolol. These haemodynamic effects were accompanied with much better symptomatic improvement in patients treated with metoprolol. The differences in change in mean PAP and PVR in two groups were statistically not significant. Our results suggest that the symptomatic patients with MS, waiting for definitive intervention for 6 months or less, would benefit if given beta blockers during this period.