Travers J, Laveneziana P, Webb K A, Kesten S, O'Donnell D E
Respiratory Investigation Unit, Department of Medicine, Queen's University, Kingston, Ont., Canada.
Respir Med. 2007 Sep;101(9):2017-24. doi: 10.1016/j.rmed.2007.03.008. Epub 2007 May 1.
Exercise limitation and exertional dyspnea are important symptoms of chronic obstructive pulmonary disease (COPD), which may be partially relieved by tiotropium. Although the mechanism of relief is multifactorial, improved dynamic ventilatory mechanics appear to be important. It is not however known whether tiotropium may also act by improving cardiovascular function during exercise.
We conducted a randomized, placebo-controlled crossover study in 18 COPD subjects with a FEV(1) 40+/-3% predicted (mean+/-SEM). Subjects inhaled either tiotropium 18 microg or placebo once daily for 7-10 days then the other intervention for a further 7-10 days after a 35-day washout period. Subjects performed constant work rate cycle exercise at 75% of maximum after each treatment period. Heart rate, blood pressure, oxygen uptake, operating lung volumes and breathing pattern were measured.
Heart rate was 7 beats/min lower at rest and throughout exercise with tiotropium compared to placebo (p=0.001). Oxygen uptake was unchanged throughout exercise. Oxygen pulse on exercise was greater by 7.4% (p<0.01) and systolic blood pressure was lower by 7 mmHg (p=0.03). The cardiac rate pressure product was reduced by 7.6% (p<0.01) with tiotropium. Exercise endurance tended to be greater with tiotropium. Reduction in heart rate on exercise correlated with an increase in inspiratory reserve volume (r=-0.50, p=0.04).
Tiotropium may improve cardiac as well as pulmonary function during exercise in COPD. We suggest that this effect may be due, in part, to improved cardiopulmonary interaction as a result of mechanical unloading of the ventilatory muscles however further study is required.
运动受限和劳力性呼吸困难是慢性阻塞性肺疾病（COPD）的重要症状，噻托溴铵可能会部分缓解这些症状。尽管缓解机制是多因素的，但改善动态通气力学似乎很重要。然而，尚不清楚噻托溴铵是否也可通过改善运动期间的心血管功能起作用。
我们对18名COPD受试者进行了一项随机、安慰剂对照的交叉研究，这些受试者的第一秒用力呼气容积（FEV₁）为预测值的40±3%（平均值±标准误）。受试者每天吸入一次18微克噻托溴铵或安慰剂，持续7 - 10天，然后在35天的洗脱期后再接受另一种干预7 - 10天。在每个治疗期后，受试者以最大运动能力的75%进行恒定工作率的自行车运动。测量心率、血压、摄氧量、有效肺容积和呼吸模式。
与安慰剂相比，使用噻托溴铵时静息及整个运动过程中的心率低7次/分钟（p = 0.001）。整个运动过程中的摄氧量未发生变化。运动时的氧脉搏增加了7.4%（p < 0.01），收缩压降低了7 mmHg（p = 0.03）。使用噻托溴铵时，心率血压乘积降低了7.6%（p < 0.01）。使用噻托溴铵时运动耐力往往更强。运动时心率的降低与吸气储备容积的增加相关（r = -0.50，p = 0.04）。
噻托溴铵可能会改善COPD患者运动期间的心脏和肺部功能。我们认为，这种作用可能部分归因于通气肌机械负荷减轻导致的心肺相互作用改善，然而还需要进一步研究。
