Effects of indacaterol versus tiotropium on exercise tolerance in patients with moderate COPD: a pilot randomized crossover study / Efeitos do indacaterol versus tiotrópio na tolerância ao exercício em pacientes com DPOC moderada: estudo cruzado randomizado piloto

Abstract Objective: To compare a once-daily long-acting β2 agonist (indacaterol 150 µg) with a once-daily long-acting anticholinergic (tiotropium 5 µg) in terms of their effects on exercise endurance (limit of tolerance, Tlim) in patients with moderate COPD. Secondary endpoints were their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Methods: This was a randomized, single-blind, crossover pilot study involving 20 patients (mean age, 60.9 ± 10.0 years; mean FEV1, 69 ± 7% of predicted). Spirometric parameters, Transition Dyspnea Index scores, Tlim, and exertional dyspnea were compared after three weeks of each treatment (with a one-week washout period between treatments). Results: Nineteen patients completed the study (one having been excluded because of COPD exacerbation). Improvement in Tlim from baseline tended to be greater after treatment with tiotropium than after treatment with indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0.06). Tlim significantly improved from baseline after treatment with tiotropium (having increased from 396 ± 319 s to 493 ± 347 s; p = 0.010) but not after treatment with indacaterol (having increased from 393 ± 246 to 401 ± 254 s; p = 0.678). There were no differences between the two treatments regarding improvements in Borg dyspnea scores and lung hyperinflation at "isotime" and peak exercise. There were also no significant differences between treatments regarding Transition Dyspnea Index scores (1.5 ± 2.1 vs. 0.9 ± 2.3; p = 0.39). Conclusions: In patients with moderate COPD, tiotropium tends to improve Tlim in comparison with indacaterol. No significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Future studies, including a larger number of patients, are required in order to confirm our findings and explore mechanistic explanations. (ClinicalTrials.gov identifier: ...

RESUMO Objetivo: Comparar um β2-agonista de longa duração administrado uma vez por dia (indacaterol 150 µg) a um anticolinérgico de longa duração administrado uma vez por dia (tiotrópio 5 µg) quanto a seus efeitos na resistência ao exercício (limite de tolerância, Tlim) em pacientes com DPOC moderada. Os desfechos secundários foram seus efeitos na hiperinsuflação pulmonar, na dispneia causada pelo exercício e na dispneia na vida diária. Métodos: Estudo piloto randomizado cruzado e simples cego com 20 pacientes (média de idade: 60,9 ± 10,0 anos; média do VEF1: 69 ± 7% do previsto). Parâmetros espirométricos, pontuação no Transition Dyspnea Index, Tlim e dispneia aos esforços foram comparados após três semanas de cada tratamento (com uma semana de intervalo entre os tratamentos). Resultados: Dezenove pacientes completaram o estudo - um foi excluído por causa de exacerbação da DPOC. A melhora no Tlim tendeu a ser maior com tiotrópio do que com indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0,06). Em comparação com os valores basais, o Tlim melhorou significativamente com tiotrópio (aumentando de 396 ± 319 s para 493 ± 347 s; p = 0,010), mas não com indacaterol (aumentando de 393 ± 246 para 401 ± 254 s; p = 0,678). Não houve diferença entre os tratamentos quanto à melhora na pontuação na escala de dispneia de Borg e na insuflação pulmonar no "isotempo" e no pico do exercício. Também não houve diferenças significativas entre os tratamentos quanto à pontuação no Transition Dyspnea Index (1,5 ± 2,1 vs. 0,9 ± 2,3; p = 0,39). Conclusões: Em pacientes com DPOC moderada, o tiotrópio tende a melhorar o Tlim em comparação com o indacaterol. Não houve diferenças significativas entre os tratamentos quanto a seus efeitos na insuflação pulmonar, na dispneia durante o exercício e na dispneia na vida diária. São necessários mais estudos, com um número maior de pacientes, para confirmar nossos achados e explorar explicações mecanicistas. (ClinicalTrials.gov ...

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.

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 effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila / Two-year follow-up of pulmonary arterial hypertension patients treated with sildenafil

FUNDAMENTO: Os efeitos de longo prazo das drogas desenvolvidas para o controle da hipertensão arterial pulmonar (HAP) são pouco conhecidos, já que os estudos multicêntricos em geral têm duração de 12 a 16 semanas. OBJETIVO: Avaliar a evolução de dois anos, em pacientes com HAP submetidos à monoterapia com sildenafila (inibidor da fosfodiesterase-5), com respeito à capacidade funcional. MÉTODOS: Vinte e quatro pacientes (idade entre 8 e 54 anos) com HAP idiopática (HAPI, n = 9) ou associada a cardiopatias congênitas (HAP-CCg, n = 15) foram tratados com sildenafila por dois anos, com doses diárias que variaram de 60 a 225 mg (três tomadas), por via oral. A capacidade física foi avaliada pela distância caminhada no teste de 6 minutos (DC6M) e pelo grau de dispneia ao final da caminhada (escala de Borg), sendo também registrada a saturação periférica de oxigênio (SpO(2)6M, oximetria de pulso). RESULTADOS: Nos 18 pacientes que completaram dois anos de seguimento, houve incremento progressivo e sustentado na DC6M, tanto no grupo HAPI (de 239 ± 160 m para 471 ± 66 m, p = 0,0076) como no grupo HAP-CCg (de 361 ± 144 m para 445 ± 96m, p = 0,0031), com melhora da dispneia ao final da caminhada (p < 0,05 em ambos). Não houve decréscimo na SpO(2)6M nos grupos considerados; em particular, pacientes com HAP-CCg evoluíram de 77 ± 20 por cento para 79 ± 16 por cento (p = 0,5248). Houve 5 óbitos (três no grupo HAPI) e uma perda de seguimento no período. CONCLUSÃO: Em dois anos de seguimento, a sildenafila mostrou-se útil no controle da condição funcional de pacientes com HAP, com melhora significante nas duas etiologias consideradas.

BACKGROUND: The long-term effects of drugs developed for the control of pulmonary arterial hypertension (PAH) are little known, since multicenter studies usually last 12 to 16 weeks. OBJECTIVE: To evaluate the two-year outcome of PAH patients receiving monotherapy with sildenafil (a phosphodiesterase-5 inhibitor), with regard to their functional capacity. METHODS: Twenty four patients (ages between 8 and 54 years) with idiopathic PAH (IPAH, n = 9) or congenital heart disease-associated PAH (CHD-PAH, n = 15) were treated with sildenafil for two years, with daily oral doses ranging from 60 to 225 mg (tid). Physical capacity was assessed by the distance walked in the 6-minute walk test (DW6M) and by the degree of dyspnea at the end of the walk (Borg scale); peripheral oxygen saturation was also recorded (SpO(2)6M, pulse oximetry). RESULTS: In the 18 patients who completed the two-year follow-up, there was a progressive and sustained increase in DW6M, both in the IPAH group (from 239 ± 160 m to 471 ± 66 m, p = 0.0076) and in the CHD-PAH group (from 361 ± 144 m to 445 ± 96m, p = 0.0031), with improvement of dyspnea at the end of the walk (p<0.05 for both groups). No decrease in SpO(2)6M was observed in the groups; in patients with CHD-PAH, in particular, SpO(2)6M went from 77 ± 20 percent to 79 ± 16 percent (p = 0.5248). Five deaths occurred (three in the IPAH group) and one patient was lost to follow-up during the study period. CONCLUSION: In a two-year follow-up, sildenafil proved useful in the control of the functional status of PAH patients, with significant improvement in both groups considered.

Efeito de curto prazo do tiotrópio nos portadores de DPOC em tratamento com B2-agonista / Short-term effect of tiotropium in COPD patients being treated with a B2 agonist

OBJETIVO: Avaliar o impacto de curto prazo do uso de tiotrópio em pacientes com DPOC grave e muito grave com queixas de dispneia apesar do tratamento com outros broncodilatadores. MÉTODOS: Estudo prospectivo incluindo pacientes com DPOC grave ou muito grave, com queixa de dispneia de pequenos esforços ou ao repouso. A cada 15 dias, o tratamento broncodilatador foi modificado: salmeterol, tiotrópio e associação salmeterol+tiotrópio. Ao final de cada regime, foram realizados testes de função pulmonar e teste de caminhada de seis minutos (TC6). Também foram avaliados o grau de dispneia e a capacidade de realização de atividades de vida diária. Para a avaliação das atividades de vida diária, foi utilizada a escala London Chest Activity of Daily Living (LCADL) validado para uso no Brasil. RESULTADOS: Foram avaliados 52 pacientes. Desses, 30 completaram o estudo. A introdução de tiotrópio como monoterapia resultou em uma melhora significativa (p < 0,05) da dispneia basal (média do escore da escala do Medical Research Council de 3,0 para 2,5) e ao final do TC6 (média do escore da escala de Borg de 6,1 para 4,5), e as diferenças foram significativas (p < 0,05 para ambos). O uso da associação salmeterol+tiotrópio resultou em um aumento significativo médio de 81 mL no VEF1 e na melhora de 5,7 pontos no escore da escala LCADL. CONCLUSÕES: A introdução de tiotrópio no tratamento de pacientes com DPOC grave a muito grave em uso de β2-agonistas de longa duração causa melhora na função pulmonar e alivio sintomático perceptível pelos pacientes a curto prazo. Esses resultados, obtidos em regime de atendimento de vida real, dão suporte ao uso da associação salmeterol+tiotrópio em protocolos de assistência específicos a esses pacientes.

OBJECTIVE: To evaluate the short-term impact of tiotropium in patients with severe or very severe COPD who complain of dyspnea despite being currently treated with other bronchodilators. METHODS: A prospective study including patients with severe or very severe COPD and complaining of dyspnea at rest or on minimal exertion. Every 15 days, the bronchodilator treatment regimen was altered, from salmeterol to tiotropium to salmeterol+tiotropium. At the end of each regimen, pulmonary function tests and the six-minute walk test (6MWT) were performed. The degree of dyspnea and the ability to perform activities of daily living were also assessed. To evaluate patient ability to perform activities of daily living, we employed the London Chest Activity of Daily Living (LCADL), validated for use in Brazil. RESULTS: We evaluated 52 patients, 30 of whom completed the study. The use of tiotropium in isolation resulted in significant improvement in dyspnea at baseline (mean Medical Research Council scale score reduced from 3.0 to 2.5) and at the end of 6MWT (mean Borg scale score reduced from 6.1 to 4.5), and the differences were significant (p < 0.05 for both). The use of the salmeterol+tiotropium combination resulted in a significant (81 mL) increase in FEV1 and a 5.7 point improvement in the LCADL score. CONCLUSIONS: The introduction of tiotropium into the treatment of patients with severe or very severe COPD and using long-acting β2 agonists improves pulmonary function and provides symptomatic relief, as perceived by patients in the short term. These results, obtained under real life treatment conditions, support the use of the salmeterol+tiotropium combination in specific treatment protocols for these patients.

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.

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.

Resposta cronotrópica ao teste cardiopulmonar após o uso de cimetidina / Effects of cimetidine on chronotropic response to cardiopulmonary exercise testing

OBJETIVO: Testar a hipótese, por meio de ensaio clínico randomizado, de que a administração de cimetidina altera a resposta cronotrópica ao exercício. MÉTODOS: Foram selecionados 24 indivíduos saudáveis, com idade entre 20 e 68 anos, não-atletas, os quais concordaram em ser submetidos a testes cardiopulmonares, após uso de placebo e de cimetidina, 400 mg, duas vezes ao dia, durante uma semana. Os testes foram realizados em esteira rolante, com protocolo de rampa com análises diretas dos gases expirados. Foi avaliada freqüência cardíaca máxima atingida, além da freqüência cardíaca de repouso e do limiar anaeróbico. RESULTADOS: Os indivíduos estudados foram igualmente distribuídos por sexo, com idade média (± desvio padrão) de 43 ±11 anos. Os exames com placebo e com cimetidina tiveram igual duração (578±90 seg vs 603±131 seg) e igual VO2 pico (35±8 ml/kg.min vs 35±8 ml/kg.min). A administração de cimetidina não apresentou efeito significativo na freqüência cardíaca de repouso (75±10 vs 74±8 bpm), no pico do esforço (176±12 vs 176±11 bpm) e, da mesma forma, também não houve diferença entre as variações das freqüências cardíacas (pico - repouso), nos dois estudos (101±14 vs 101±13 bpm). CONCLUSÃO: A administração de cimetidina por sete dias não altera a resposta cronotrópica ao exercício.

Efecto del bromuro de ipratropio sobre la hiperinflación pulmonar dinámica en pacientes con enfermedad pulmonar obstructiva crónica / Effect of ipratropium bromide on lung dynamic hyperinflation in patients with chronic obstructive lung disease

BACKGROUND: The six minute walk test (6 MW) elicits dynamic hyperinflation (DH) in severe COPD patients, which can be evaluated by reductions in inspiratory capacity (IC). Although IC is currently used to determine the effects of bronchodilators on DH during exercise tests on a cycle ergometer, its usefulness during a walking test has not been evaluated. AIM: To study the acute effects of ipratropium bromide (IB) on forced expiratory volume at l second (FEV1) and IC at rest and on DH during exercise assessed by the 6 MW. SUBJECTS AND METHODS: Fifteen stable COPD patients were randomly allocated in a double-blind, placebo-controlled, crossover fashion to 2 treatment periods using a single dose of nebulized IB 500 mg or placebo. Spirometry, including IC, and 6 MW were measured at baseline and after IB and placebo. IC was also measured 15 min after exercise. Dyspnea, oxygen saturation (SpO2) and heart rate were assessed at the end of exercise. RESULTS: After IB, 8/15 patients exhibited a clinically significant increase in IC (> or = 10 per cent predicted). A similar increase in FEV1 was observed in only one patient. No changes were observed with placebo. A significant increase in 6 MW from baseline (p = 0.007) was found after IB (45 +/- 14 m) compared to placebo (0.5 +/- 9 m), whereas dyspnea was significantly lower. Inspiratory capacity fell after 6 MW with both treatments, but it reached their baseline values at 15 min after exercise only with IB. CONCLUSIONS: Our results demonstrate that IC provides additional information to conventional spirometry on the acute effects of bronchodilators and confirm its value to assess DH during a walking test.

Teste de esforço cardiopulmonar durante estimulaçäo colinérgica com dose única de piridostigmina em indivíduos saudáveis / Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

OBJETIVE: The evaluation, by exercise stress testing, of the cardiorespiratory effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor. METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of hemodynamic and ventilation variables of 10 healthy subjects who underwent three exercise stress tests (the first for adaptation and determination of tolerance to exercise, the other two after administration of placebo or 45mg of PYR). RESULTS: Heart rate at rest was: 68 + or - 3 vs 68 + or - 3bpm before and after placebo, respectively (P=0.38); 70 + or - 2 vs 59 + or - 2bpm, before and after pyridostigmine, respectively (P<0.01). During exercise, relative to placebo: a significantly lower heart rate after PYR at, respectively, 20 per cent (P=0.02), 40 per cent (P=0.03), 80 per cent (P=0.05) and 100 per cent (P=0.02) of peak effort was observed. No significant differences were observed in arterial blood pressure, oxygen consumption at submaximal and maximal effort, exercise duration, respiratory ratio, CO2 production, ventilation threshold, minute ventilation, and oxygen pulse. CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Effects of caffeine on time to exhaustion in exercise performed below and above the anaerobic threshold

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10 percent below and 10 percent above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10 percent below and 10 percent above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was singificantly lower (CAF = 14.1 + 2.5 vs PLA = 16.6 + 2.4) and time to exhaustion was significantly higher (CAF = 46.54 + 8.05 min vs PLA = 32.42 + 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 + 2.7 vs PLA = 17.6 + 2.3) and time to exhaustion (CAF = 18.45 + 7.28 min vs PLA = 19.17 + 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that decrease of perceived exertion can be involved in this process.

Efecto del carvedilol sobre la función ventricular y capacidad de ejercicio en insuficiencia cardíaca / Effect of carvedilol on ventricular function and exercise capacity in heart failure

Para evaluar el efecto del carvedilol, bloqueante b1 y a1, en pacientes con insuficiencia cardíaca se llevó a cabo un ensayo clínico a doble ciego con asignación al azar, valorándose la fracción de eyección ventricular izquierda y capacidad de ejercicio medida por ergometría. Se incluyeron 33 pacientes, 14 recibieron placebo y 19 carvedilol en dosis creciente hasta 25 mg/día, agregado a la terapia convencional. No hubo diferencias en las características basales de ambos grupos. La fracción de eyección basal fue 26,22 por ciento (ñ 8) y 22 por ciento (ñ 5,7) (p = 0,11) y el tiempo de ejercicio 9,52 min (ñ 3,6) y 9 min (ñ 4) (p = 0,73), para los grupos carvedilol y placebo respectivamente. La fracción de eyección, al final del estudio, fue 34,5 por ciento (ñ 12) y 24,5 por ciento (ñ 7,8) (p = 0,03) y el tiempo de ejercicio (en minutos) 13,8 (ñ 2,3) y 10,6 (ñ 3,4) (p = 0,02) para los grupos tratados y control. El carvedilol administrado crónicamente a pacientes con insuficiencia cardíaca aumenta significativamente la fracción de eyección ventricular izquierda y la capacidad de ejercicio

Indigenous free radical scavenger MAK 4 and 5 in angina pectoris. Is it only a placebo?

Thirty patients were evaluated to study the effect of Maharishi Amrit Kalsh (MAK) 4 & 5 on Angina pectoris. The mean angina frequency per month was 8.87. Twelve lead ECG, computerized TMT and echo studies were done initially, at 6 months, and after 2 years in all cases. Ten grams of MAK 4 paste was given daily in two divided doses, each followed by a MAK 5 tablet, for six months. Vasodilator and antihypertensive drugs were continued on ethical grounds. Twenty-four patients (80%) out of the total 30 reported a significant improvement after 6 months of therapy. The mean angina frequency per month improved from 8.87 to 3.03. All patients reported a sense of well being. Five out of 11 hypertensive patients reported a fall in systolic blood pressure. Lipid profile showed a rise in HDL which was statistically insignificant. Improved exercise tolerance was observed in 10 cases (33.33%) after 6 months of therapy and this effect was sustained even at 2 years. ECG and echo studies were inconclusive. No side effects or drug interactions were seen. This beneficial effect observed is probably as a result of free radical scavenging property of MAK on 'Reactive Oxygen Species' or an inhibitory effect on lipid peroxidation; or by its inhibitory action on platelet aggregation or all these in synergism.

Antianginal and cardioprotective effects of Terminalia arjuna, an indigenous drug, in coronary artery disease.

The effect of bark powder of Terminalia arjuna, an indigenous drug, on anginal frequency, blood pressure, body mass index, blood sugar, cholesterol and HDL-cholesterol was studied in 15 stable (Group A) and 5 unstable (Group B) angina patients before and 3 months after T. arjuna therapy. Tread mill test (TMT) and echocardiographic left ventricular ejection fraction was evaluated in some cases. There was 50% reduction in anginal episodes in Group A cases (P < 0.01). TMT performance improved from moderate to mild changes in 5 patients and one with mild changes became negative for ischemia. The time to the onset of angina and appearance of ST-T changes on TMT after T. arjuna was delayed significantly. However, in patients with unstable angina there was an insignificant reduction in anginal frequency. These patients also needed diltiazem, B-blockers and nitroglycerine in addition to T. arjuna. The drug lowered systolic blood pressure and body mass index to a significant level (p < 0.05) and increased HDL-cholesterol only slightly along with marginal improvement in left ventricular ejection fraction in stable angina patients. There were no deleterious effects on liver or kidney functions. Our results suggest that monotherapy with T. arjuna is fairly effective in patients with symptoms of stable angina pectoris. However, it has a limited role in unstable angina.

Use of captopril as an isolated agent for the management of stable angina pectoris--a double blind randomised trial.

In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation.

Interpretation of treadmill stress test in patients with coronary artery disease receiving beta blocker therapy.

Graded maximal treadmill exercise responses were studied before and after beta blockade (atenolol 100 mg once daily for 2 weeks) in 20 male patients with chronic stable angina. Beta-blocking effect consisted of significant reduction of resting heart rate (HR) by 21%, systolic blood pressure (SBP) by 12% and rate pressure product (RPP) by 30%. While the maximum exercise capacity was marginally increased by mean 1.7 min +/- 1.6 SD (P less than 0.001) under the influence of therapy, peak HR, SBP and maximum RPP were significantly lower (P less than 0.001) than in preatenolol exercise tests. Similarly, while the configuration and magnitude of ST segment depression did not differ materially between the pre and post atenolol tests, onset time of ST change was delayed and offset time shortened significantly. These parameters cannot be relied upon to assess the extent and severity of coronary artery disease (CAD) if stress test is carried out while the patient is on a beta-blocking drug. The overall sensitivity of the stress test to detect coronary disease is, however, not likely to be compromised because of negligible influence of beta-blockers upon ST segment depression provided maximally tolerated (not submaximal) exercise is performed. ST/HR slope, an exercise test variable known to correlate well with the extent of CAD, was shown to be uninfluenced by beta-blockade. Its measurement is therefore recommended in interpreting stress tests performed in patients receiving beta-blocker therapy. This, however, requires a meticulously prepared protocol of recording computer averaged QRST complexes and multilead ECG tracings at very frequent intervals throughout the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous oxyfedrine on exercise in patients with ischaemic heart disease.

In a double blind crossover trial, acute effects of 8 mg intravenous oxyfedrine were compared with those of placebo in 18 patients with stable effort angina assessed by treadmill exercise testing. In the resting state, oxyfedrine caused an increase in heart rate (84 +/- 23 to 103 +/- 19 bpm, p less than 0.01), systolic blood pressure (123 +/- 16 to 133 +/- 20 mmHg, p less than 0.01) and double product (11 x 10(3) +/- 2 x 10(3) to 13.7 x 10(3) +/- 3.1 x 10(3), p less than 0.01) as compared to placebo. However, these parameters were not significantly different at the end of first or second stage of the treadmill test (p = NS). Time to one mm ST segment depression was increased with oxyfedrine as compared to placebo (1.5 +/- 1.5 to 1.9 +/- 1.5 minutes, p less than 0.05). Oxyfedrine did not increase the total duration of exercise (4.1 +/- 1.0 to 4.7 +/- 2.2 minutes, p = NS) or time to ischaemic symptoms (2.7 +/- 1.3 to 2.9 +/- 1.9 minutes, p = NS). The total work done was significantly more on oxyfedrine 312 +/- 189 joules/kg to 370 +/- 209 joules/kg, p less than 0.01) as also the double product achieved (20.6 x 10(3) +/- 6.1 x 10(3) to 22.5 x 10(3) +/- 6.4 x 10(3), p less than 0.01). It is concluded that intravenous oxyfedrine improves exercise capacity in patients with stable effort angina presumably by reducing myocardial ischaemia.