Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis
Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis
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DOI：
10.1053/jhep.2003.50053
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发表时间：
2003-02-01
期刊：
影响因子：
13.5
通讯作者：
Rodés, J
中科院分区：
文献类型：
--
作者：
Bellis, L;Berzigotti, A;Rodés, J
肝硬化患者餐后充血与门静脉压力显著升高相关，这可能导致胃食管静脉曲张进行性扩张和破裂。在肝硬化中，肝脏产生一氧化氮（NO）不足可能会损害预期的肝血管舒张反应，从而进一步夸大餐后门静脉压力的增加。本研究旨在探讨低剂量口服一氧化氮是否可以抵消餐后门静脉压力峰值。23例门脉高压肝硬化患者，其中8例正在接受普萘洛尔治疗，随机分为口服单硝酸5-异山梨酯（ISMN; 10 mg; n = 11）或安慰剂（n = 12）组，15分钟后给予标准液体餐。在基线和饭后15、30和45分钟测量肝静脉压梯度（HVPG）、平均动脉压（MAP）和肝血流量（HBF）。与安慰剂相比，ISMN显著降低餐后门静脉压升高（HVPG峰值升高：2.4 +/- 1.4 mm Hg vs. 5.2 +/- 2.1 mm Hg, P = 0.002）。两组HBF的百分比增加相似。ISMN组MAP略有下降（-7.5% +/- 0.5%；与基线相比P < 0.01）。慢性心得安治疗的患者也观察到这些影响。综上所述，低剂量ISMN补充肝脏NO可有效降低肝硬化患者餐后门静脉压力升高，对动脉压力仅有轻微影响。在服用心得安的患者中也观察到同样的情况。我们的研究结果表明，基于选择性肝NO输送的治疗策略可能改善门静脉高压症的治疗。
Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo (n = 12) and a standard liquid meal 15 minutes later. Hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and hepatic blood flow (HBF) were measured at baseline and 15, 30, and 45 minutes after a meal. ISMN significantly attenuated the postprandial increase in portal pressure as compared with placebo (peak HVPG increase: 2.4 +/- 1.4 mm Hg vs. 5.2 +/- 2.1 mm Hg, P = .002). Percentual increases in HBF were similar in both groups. MAP decreased slightly in ISMN group (-7.5% +/- .5%; P < .01 vs. baseline). These effects were also observed in patients on chronic propranolol therapy. In conclusion, hepatic NO supplementation by low doses of ISMN effectively reduces the postprandial increase of portal pressure in cirrhosis, with only a mild effect on arterial pressure. The same was observed in patients receiving propranolol. Our results suggest that therapeutic strategies based on selective hepatic NO delivery may improve the treatment of portal hypertension.