Ghofrani Hossein Ardeschir, Wiedemann Ralph, Rose Frank, Schermuly Ralph T, Olschewski Horst, Weissmann Norbert, Gunther Andreas, Walmrath Dieter, Seeger Werner, Grimminger Friedrich
Department of Internal Medicine, University Hospital, Justus-Liebig-University, 35392 Giessen, Germany.
Lancet. 2002 Sep 21;360(9337):895-900. doi: 10.1016/S0140-6736(02)11024-5.
Lung fibrosis can be complicated by pulmonary hypertension, limiting exercise tolerance and life expectancy. Furthermore, vasodilators might cause deterioration in gas exchange. Our aim was to compare acute effects of sildenafil, nitric oxide, and epoprostenol in individuals with pulmonary hypertension secondary to lung fibrosis.
We did a randomised controlled, open-label trial, in 16 individuals admitted to our hospital with pulmonary hypertension secondary to lung fibrosis. After inhalation of nitric oxide (10-20 ppm), we assigned patients to either maximum tolerated dose of intravenous epoprostenol (mean 8.0 ng/kg per min; n=8) or oral sildenafil (50 mg; n=8). Our primary objective was to assess pulmonary vasodilative potency (decrease in pulmonary vascular resistance index) of sildenafil by comparison with inhaled nitric oxide and infused epoprostenol. Analyses were by intention to treat.
Pulmonary vascular resistance index was reduced by nitric oxide (-21.9%, 95% CI -14.1 to -36.2), epoprostenol (-36.9%, -24.4 to -59.6), and sildenafil (-32.5%, -10.2 to -54.1). However, ratio of pulmonary to systemic vascular resistance decreased only in individuals who received nitric oxide and sildenafil. Baseline measurement of multiple-inert-gas elimination showed right-to-left shunt flow (4.8%, 0.0-28.2) and little perfusion of low ventilation(V)/perfusion(Q) areas (0.1%, 0.0-13.0). Prostacyclin increased V/Q mismatch (shunt 16.8%, 10.8-35.9; low V/Q 3.8%, 0.0-13.0) and decreased arterial oxygenation. By contrast, nitric oxide (4.5%, 0.0-18.0; 0.0%, 0.0-17.3) and sildenafil (3.3%, 0.0-11.3; 0.0%, 0.0-12.4) maintained V/Q matching, with raised arterial partial pressure of oxygen (14.3 mm Hg, -1.7 to 31.3) noted for sildenafil. We recorded no adverse events.
Sildenafil causes preferential pulmonary vasodilation and improves gas exchange in patients with severe lung fibrosis and secondary pulmonary hypertension.
肺纤维化可并发肺动脉高压，限制运动耐量和预期寿命。此外，血管扩张剂可能导致气体交换恶化。我们的目的是比较西地那非、一氧化氮和依前列醇对继发于肺纤维化的肺动脉高压患者的急性影响。
我们对16例因继发于肺纤维化的肺动脉高压而入住我院的患者进行了一项随机对照、开放标签试验。吸入一氧化氮（10 - 20 ppm）后，我们将患者分为静脉注射依前列醇最大耐受剂量组（平均8.0 ng/kg每分钟；n = 8）或口服西地那非组（50 mg；n = 8）。我们的主要目标是通过与吸入一氧化氮和输注依前列醇比较，评估西地那非的肺血管扩张效力（肺血管阻力指数降低情况）。分析采用意向性治疗。
一氧化氮使肺血管阻力指数降低（-21.9%，95%置信区间 -14.1至 -36.2），依前列醇降低（-36.9%，-24.4至 -59.6），西地那非降低（-32.5%，-10.2至 -54.1）。然而，仅在接受一氧化氮和西地那非的个体中，肺血管与体循环血管阻力之比降低。多次惰性气体消除的基线测量显示存在右向左分流（4.8%，0.0 - 28.2），低通气（V）/灌注（Q）区域灌注较少（0.1%，0.0 - 13.0）。前列环素增加了V/Q不匹配（分流16.8%，10.8 - 35.9；低V/Q 3.8%，0.0 - 13.0）并降低了动脉氧合。相比之下，一氧化氮（4.5%，0.0 - 18.0；0.0%，0.0 - 17.3）和西地那非（3.3%，0.0 - 11.3；0.0%，0.0 - 12.4）维持了V/Q匹配，西地那非使动脉血氧分压升高（14.3 mmHg，-1.7至31.3）。我们未记录到不良事件。
西地那非可使严重肺纤维化和继发肺动脉高压患者的肺血管优先扩张并改善气体交换。
