RESUMO
BACKGROUND: Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O(2) delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung hyperinflation after the inhalation of bronchodilators would improve skeletal muscle oxygenation during exercise was tested. METHODS: Twelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV(1))=38.5+/-12.9% predicted; Pao(2)>60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70-80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de)oxygenation (approximately fractional O(2) extraction) was determined in the vastus lateralis by changes (Delta) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from near-infrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. RESULTS: Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (454+/-131 s vs 321+/-140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O(2) uptake V(o(2))were accelerated with active treatment; Delta[HHb] dynamics, however, were delayed by approximately 78% and the signal amplitude diminished by approximately 21% (p<0.01). Consequently, the ratio between V(o(2)) and Delta[HHb] dynamics decreased, suggesting improved microvascular O(2) delivery (tau-V(o(2))/MRT-Delta[HHb]=4.48+/-1.57 s vs 2.08+/-1.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in tau-V(o(2))/MRT-Delta[HHb] (p<0.01). CONCLUSIONS: Decreases in operating lung volumes after the inhalation of bronchodilators are associated with faster 'central' cardiovascular adjustments to high-intensity exercise with beneficial consequences on muscle oxygenation in patients with moderate to severe COPD.
Assuntos
Broncodilatadores/farmacologia , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas Adrenérgicos beta/farmacologia , Agonistas Adrenérgicos beta/uso terapêutico , Idoso , Albuterol/farmacologia , Albuterol/uso terapêutico , Brasil , Broncodilatadores/uso terapêutico , Antagonistas Colinérgicos/farmacologia , Antagonistas Colinérgicos/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço/métodos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Ipratrópio/farmacologia , Ipratrópio/uso terapêutico , Perna (Membro)/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Capacidade Vital/efeitos dos fármacosRESUMO
Muscle vascular dysfunction, a hallmark of chronic diseases such as heart failure and diabetes, impairs the matching of blood flow (Q(m)) to O(2) utilization (V(O(2m))) following exercise onset. One recently described consequence of this behavior is that arterial-venous O(2) difference [(a-v)(O(2)), the mirror image of muscle vascular oxygenation] transiently overshoots the subsequent steady-state and, in so doing, may provide important information regarding Q(m) versus V(O(2m)) dynamics. Using computer simulations, we tested the hypothesis that key parameters of the (a-v)(O(2)) overshoot - peak response, downward time constant (tau(D)), and total area - would relate quantitatively to Q(m) kinetics. Our results demonstrated significant proportionality (all p<0.01) between Q(m) mean response time and peak (r(2)=0.56), tau(D) (r(2)=72) and total area (r(2)=0.97) of (a-v)(O(2)) overshoot. These results suggest that analysis of (a-v)(O(2)) or its proxy, muscle vascular oxygenation [measured using near-infrared spectroscopy or phosphorescence quenching], provides valuable information regarding blood flow and vascular function particularly in reference to V(O(2m)) kinetics.
Assuntos
Exercício Físico/fisiologia , Microcirculação/fisiologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Ventilação Pulmonar/fisiologia , Artérias/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Simulação por Computador , Humanos , Cinética , Modelos Lineares , Modelos Biológicos , Fluxo Sanguíneo Regional/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Veias/fisiologiaRESUMO
RATIONALE: Normoxic heliox (mixture of 79% He and 21% O(2)) may enhance exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). It remains to be determined whether part of these beneficial effects could be ascribed to increased O(2) delivery (O(2)DEL) to locomotor muscles. OBJECTIVES: To investigate the effects of heliox on peripheral O(2)DEL and utilization during exercise in moderate to severe COPD. METHODS: Twelve mildly hypoxic or nonhypoxemic men (FEV(1) = 45.0 +/- 13.0% predicted) underwent constant-work rate tests (70-80% peak) to the limit of tolerance while receiving heliox or room air. Near-infrared spectroscopy determined changes (Delta) in leg muscle deoxygenation (deoxyhemoglobin concentration [HHb], an index of fractional O(2) extraction), and surface electromyography estimated muscle fiber recruitment (n = 5). Q and Sp(O(2)) were monitored by impedance cardiography and pulse oximetry, respectively. MEASUREMENTS AND MAIN RESULTS: Heliox significantly decreased dynamic hyperinflation and increased exercise tolerance compared with room air (640 +/- 95 s vs. 371 +/- 100 s; P < 0.01). Heliox also accelerated on-exercise dynamics of Q, which were accompanied by faster O(2) uptake kinetics and slower Delta[HHb] responses (P < 0.05). During steady-state exercise, Sp(O(2))-corrected Delta[HHb] values decreased with heliox despite no significant changes in cardiac output. Muscle fiber recruitment and leg effort scores were also diminished (P < 0.05). On a multiple regression analysis, reductions in dynamic hyperinflation, dyspnea, and Delta[HHb] were independently related to improvements in exercise tolerance with heliox (R(2) = 0.91; P < 0.01). CONCLUSIONS: Heliox increases lower limb O(2)DEL and utilization during dynamic exercise in patients with moderate to severe COPD. These effects enhance exercise tolerance in this patient population.
Assuntos
Tolerância ao Exercício/fisiologia , Hélio/administração & dosagem , Consumo de Oxigênio/fisiologia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Estudos Cross-Over , Teste de Esforço , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O(2) delivery to uptake during exercise. We tested the hypothesis that, along with slowed Vo(2)(p) kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Qt) following the onset of heavy-intensity exercise. We measured Vo(2)(p), Qt (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly (P < 0.05) lower in patients and related to the kinetics of Vo(2)(p) (r = -0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of Vo(2)(p) (42 +/- 13 vs. 73 +/- 24 s) and Qt (67 +/- 11 vs. 96 +/- 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 +/- 2.4 vs. 16.5 +/- 3.4 s). Consequently, the time constant ratio of O(2) uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O(2) delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O(2) delivery and utilization and may contribute to the slower Vo(2)(p) kinetics compared with age-matched controls.