Colle Isabelle, De Vriese An S, Van Vlierberghe Hans, Lameire Norbert H, DeVos Martine
Department of Medicine, Ghent University Hospital, Ghent, Belgium.
Liver Int. 2004 Feb;24(1):63-8. doi: 10.1111/j.1478-3231.2004.00892.x.
Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis.
Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01-10 mg/kg) and after intravenous (i.v.) (0.01-10 mg/kg) administration of sildenafil.
Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL.
Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis.
西地那非是海绵体内特异性环磷酸鸟苷（cGMP）磷酸二酯酶5型（PDE-V）的选择性抑制剂。PDE-V也存在于肠系膜动脉中。肝硬化常伴有内脏血管扩张，这归因于局部一氧化氮（NO）过度生成。由于西地那非可增强NO的作用，它可能会进一步降低肠系膜血管张力并增加门静脉血流量。本研究旨在评估西地那非对肝硬化实验模型中全身和内脏血流动力学的影响。
通过结扎雄性Wistar大鼠胆总管（CBDL，n = 8）诱导继发性胆汁性肝硬化；对照大鼠进行假手术（假手术组，n = 7）。在肠系膜内（0.01 - 10 mg/kg）和静脉内（i.v.）（0.01 - 10 mg/kg）给予西地那非后，测量平均动脉压（MAP）、门静脉压（PVP）和肠系膜动脉血流量（MBF）。
CBDL组的基线PVP显著高于假手术组大鼠，而CBDL组的基线MAP趋于更低，MBF趋于更高。肠系膜内注射和静脉注射西地那非均以剂量依赖性方式显著降低MAP，并增加MBF和PVP。CBDL组MAP的降低幅度明显小于假手术组大鼠。CBDL组MBF的增加幅度明显低于假手术组大鼠。假手术组大鼠PVP的升高幅度往往比CBDL组更显著。
西地那非增加MBF和PVP并导致全身性低血压。在肝硬化中这些作用不太明显，提示血管对西地那非反应性降低。尽管肝硬化动物中PVP的升高幅度小于对照组，但仍可能存在出血并发症风险。在给肝硬化患者开具西地那非之前，有必要进行进一步研究。
