Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Clin Gastroenterol Hepatol. 2010 Jun;8(6):546-9. doi: 10.1016/j.cgh.2010.01.017. Epub 2010 Feb 6.
BACKGROUND & AIMS: The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The phosphodiesterase-5 (PDE-V) inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious. The aim of this study was to evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study.
Twelve patients with compensated cirrhosis and baseline hepatic venous pressure gradient (HVPG) >5 mm Hg received 25 mg of oral sildenafil. Mean arterial pressure (MAP), heart rate (HR), and HVPG were repeated after 30 and 60 minutes in 9/12 patients at 90 minutes (after an additional 25 mg of sildenafil). HVPG tracings were read by 3 blinded observers.
All 12 patients were Child A with median MAP of 92 mm Hg (interquartile range, 83-94) and HVPG 10.4 mm Hg (interquartile range, 6.6-13.0). While MAP decreased significantly at all time points, sildenafil had no effect on HVPG.
As shown with other vasodilators in compensated cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction reduces MAP without reducing portal pressure. The search should continue for specific intrahepatic vasodilators.
对于早期代偿性肝硬化患者，降低门静脉压力可能对增加肝内血管舒张的药物比降低门静脉流入的药物更敏感。磷酸二酯酶-5（PDE-V）抑制剂西地那非可能通过降低肝内阻力来降低门静脉压力，但它的全身血管舒张作用可能是有害的。本研究旨在评估西地那非对开放标签初步研究中系统性和门静脉血液动力学的影响。
12 例代偿性肝硬化且基线肝静脉压力梯度（HVPG）>5mmHg 的患者接受 25mg 口服西地那非。9/12 例患者在 30 分钟和 60 分钟时重复测量平均动脉压（MAP）、心率（HR）和 HVPG，在 90 分钟时（另外给予 25mg 西地那非后）重复测量 9/12 例患者的 MAP。由 3 名盲法观察者读取 HVPG 描记图。
所有 12 例患者均为 Child A，MAP 中位数为 92mmHg（四分位间距为 83-94），HVPG 为 10.4mmHg（四分位间距为 6.6-13.0）。虽然 MAP 在所有时间点均显著下降，但西地那非对 HVPG 没有影响。
与其他在代偿性肝硬化患者中使用的血管扩张剂一样，治疗勃起功能障碍的西地那非的治疗剂量可降低 MAP，而不降低门静脉压力。应继续寻找特定的肝内血管扩张剂。
