Damy Thibaud, Hobkirk James, Walters Mandy, Ciobanu Andrea, Rigby Alan S, Kallvikbacka-Bennett Anna, Guellich Aziz, Dubois-Randé Jean-Luc, Hittinger Luc, Clark Andrew L, Cleland John G F
*Department of Cardiology, University of Hull, Castle Hill Hospital, Kingston upon Hull, United Kingdom; †Department of Cardiology, AP-HP Groupe, Henri-Mondor Albert-Chenevier, Créteil, France; ‡INSERM, Unité U955, Créteil, France; §Université Paris Est, Faculté de Médecine and DHU ATVB and INSERM Clinical Investigation Center 006, Créteil, France; and ¶National Heart & Lung Institute, Imperial College, London, United Kingdom.
J Cardiovasc Pharmacol. 2015 Sep;66(3):229-38. doi: 10.1097/FJC.0000000000000262.
Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects.
In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil.
Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.
肺动脉高压与慢性心力衰竭（CHF）患者的不良预后相关，可能是一个治疗靶点。我们的目的是建立一种用于研究CHF患者肺血管反应性的无创模型，并描述西地那非的急性心血管效应。
在一项交叉研究中，18例CHF患者在静息和运动时参与了4次试验[西地那非（2×20mg）/或安慰剂（双盲），同时呼吸空气或15%氧气]。记录氧饱和度（SaO2）和全身血管阻力。通过超声心动图测量左、右心室（RV）功能和三尖瓣收缩期压力梯度（RVTG）。静息时，低氧导致SaO2下降（P = 0.001），RVTG升高（5±4mmHg；P = 0.001）。西地那非降低了SaO2（-1±2%；P = 0.043）、全身血管阻力（-87±156dyn·s·cm；P = 0.034）和RVTG（-2±5mmHg；P = 0.05）。运动导致心输出量增加（2.1±1.8L/min；P < 0.001）和RVTG升高（19±11mmHg；P < 0.0001）。低氧并未减弱西地那非对RVTG的降低作用。西地那非也未显著降低运动引起的RVTG升高。
静息呼吸空气时，西地那非降低SaO2，低氧并未使其加重，提示肺通气不良区域肺血管扩张导致通气-灌注不匹配增加。西地那非降低静息时的RVTG，并防止低氧而非运动引起的RVTG升高。本研究表明该模型在评估肺动脉高压新疗法方面的有用性。
