Voswinckel Robert, Reichenberger Frank, Enke Beate, Kreckel Andre, Krick Stefanie, Gall Henning, Schermuly Ralph Theo, Grimminger Friedrich, Rubin Lewis J, Olschewski Horst, Seeger Werner, Ghofrani Hossein A
Department of Internal Medicine, University of Giessen Lung Center, University Hospital Giessen and Marburg GmbH, Giessen, Germany.
Pulm Pharmacol Ther. 2008 Oct;21(5):824-32. doi: 10.1016/j.pupt.2008.07.003. Epub 2008 Jul 9.
Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension.
Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5).
Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed.
The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.
吸入用曲前列尼尔最近被开发用于治疗肺动脉高压（PAH）。我们在一项针对毛细血管前性肺动脉高压患者的开放标签研究中，调查了口服西地那非与吸入用曲前列尼尔联合应用的安全性和急性血流动力学效应。
在右心导管检查期间，对连续的肺动脉高压（PAH；n = 28）、无法手术的慢性血栓栓塞性肺动脉高压（CTEPH；n = 17）和肺纤维化相关性肺动脉高压（n = 5）患者，依次应用吸入一氧化氮（20ppm；n = 50）、西地那非（50mg；n = 50）和吸入用曲前列尼尔（15μg；n = 25或30μg；n = 25）。
吸入一氧化氮使肺血管阻力（PVR）降至基线值的87.3±5.1%，平均肺动脉压（PAP）降至89.7±3.5%，心输出量（CO）增加至102.4±2.9%。西地那非使PVR降至80.1±5.0%，mPAP降至86.5±2.9%，CO增加至103.8±3.2%。在西地那非给药1小时后吸入的曲前列尼尔，使PVR降至66.3±3.8%，mPAP降至77.8±3.3%，CO增加至107.1±3.3%（均值±95%置信区间）。亚组分析显示PAH和CTEPH患者有相似的急性血流动力学效应。在6例已有气体交换受限的患者中，西地那非和曲前列尼尔未改变通气/灌注分布测量结果。未观察到相关副作用。
西地那非与吸入用曲前列尼尔联合应用耐受性良好，在肺动脉高压患者中可诱导相加的、肺选择性血管舒张。这对于PAH和CTEPH患者的长期治疗可能也具有重要意义。
