Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension
Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension
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DOI：
10.1164/rccm.200907-0988oc
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发表时间：
2010-02-01
影响因子：
24.7
通讯作者：
Albert Barbera, Joan
中科院分区：
文献类型：
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作者：
Blanco, Isabel;Gimeno, Elena;Albert Barbera, Joan
理由：西地那非是一种磷酸二酯酶-5抑制剂，可用于治疗慢性阻塞性肺疾病（COPD）的肺动脉高压（PH）。然而，在这种情况下，血管扩张剂可能抑制缺氧肺血管收缩和损害气体交换。目的：评估西地那非对copd相关性ph患者急性血流动力学和气体交换的影响。方法：我们在20例copd相关性ph患者中进行了一项随机剂量比较试验。11例患者使用20mg西地那非，9例患者使用40mg西地那非。肺血流动力学和气体交换，包括通气-灌注((V) over dot（A)/(Q) over dot）关系，在静止和恒定工作速率运动期间，西地那非给药前和给药后1小时进行评估。测量结果和主要结果：两种剂量的西地那非均可降低静息和运动时的平均肺动脉压（PAP），两者之间无差异。总的来说，PAP在休息时降低了6毫米汞柱（95%置信区间[95% CI]， -7至-4），在运动时降低了-11毫米汞柱（95% Cl， -14至-8）。西地那非后，静息时Pa-O2降低-6毫米汞柱（95% Cl， -8至-4），因为(V) /(Q) /点比较低的单位灌注增加，剂量间无差异。在服用西地那非后的运动期间，Pa-O2 （95% Cl， -3至0.2 mm Hg）或(V) /(A)/(Q) / dot关系没有变化。西地那非引起的静止时Pa-O2和(V) over dot(A)/(Q) over dot分布的变化与其各自的基线值相关。结论：在copd相关PH患者中，西地那非可改善静息和运动时的肺血流动力学。这种作用伴随着对缺氧血管收缩的抑制，这损害了静止时的动脉氧合。在慢性阻塞性肺病中使用西地那非应谨慎，并应密切监测血气。
Rationale: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition.Objectives: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.Methods: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion ((V) over dot(A)/(Q) over dot) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.Measurements and Main Results: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased-6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% Cl, -14 to -8) during exercise. After sildenafil, Pa-O2, decreased -6 mm Hg (95% Cl, -8 to -4) at rest because of increased perfusion in units with low (V) over dot(A)/(Q) over dot ratio, without differences between doses. No change in Pa-O2 (95% Cl, -3 to 0.2 mm Hg) or (V) over dot(A)/(Q) over dot relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa-O2 and (V) over dot(A)/(Q) over dot distributions at rest correlated with their respective values at baseline.Conclusions: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases.