Clemmesen Jens-Otto, Giraldi Annamaria, Ott Peter, Dalhoff Kim, Hansen Bent-Adel, Larsen Fin-Stolze
Department of Hepatology A-2121, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark.
World J Gastroenterol. 2008 Oct 28;14(40):6208-12. doi: 10.3748/wjg.14.6208.
To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown.
Ten patients with biopsy proven cirrhosis (five females/five males, mean age 54 +/- 8 years) and an HVPG above 12 mmHg were studied after informed consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick's principle, with correction for non-steady state.
The plasma concentration of sildenafil was 222 +/- 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 +/- 7 mmHg to 66 +/- 12 mmHg, P = 0.003, while the splanchnic blood flow and oxygen consumption remained unchanged at 1.14 +/- 0.71 L/min and 2.3 +/- 0.6 mmol/min, respectively. Also the HVPG remained unchanged (18 +/- 2 mmHg vs 16 +/- 2 mmHg) with individual changes ranging from -8 mmHg to +2 mmHg. In seven patients, HVPG decreased and in three it increased.
In spite of arterial blood pressure decreases 80 min after administration of the phosphodiesterase type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG.
研究西地那非是否能增加肝硬化患者的内脏血流量并改变肝静脉压力梯度(HVPG)。5型磷酸二酯酶抑制剂在终末期肝病患者勃起功能障碍和肺动脉高压的治疗中具有重要价值。然而,5型磷酸二酯酶抑制剂对内脏血流量和门静脉高压的影响基本未知。
在获得知情同意后,对10例经活检证实为肝硬化的患者(5名女性/5名男性,平均年龄54±8岁)且HVPG高于12 mmHg进行了研究。在口服50 mg西地那非前及服药80分钟后,在肝静脉插管期间测量内脏血流量和HVPG。采用吲哚菁绿清除技术和菲克原理估算血流量,并对非稳态进行校正。
给药80分钟后西地那非的血浆浓度为222±136 ng/mL。平均动脉血压从77±7 mmHg降至66±12 mmHg,P = 0.003,而内脏血流量和氧耗分别维持在1.14±0.71 L/min和2.3±0.6 mmol/min不变。HVPG也保持不变(18±2 mmHg对16±2 mmHg),个体变化范围为-8 mmHg至+2 mmHg。7例患者的HVPG下降,3例患者的HVPG上升。
尽管在给予5型磷酸二酯酶抑制剂西地那非80分钟后动脉血压下降,但本研究未发现其对内脏血流量、氧耗或HVPG有任何临床相关影响。