Escorsell A, Feu F, Bordas J M, García-Pagán J C, Luca A, Bosch J, Rodés J
Hepatic Haemodynamic Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
J Hepatol. 1996 Apr;24(4):423-9. doi: 10.1016/s0168-8278(96)80162-0.
Isosorbide-5-mononitrate is a long-acting nitrovasodilator which was introduced for the treatment of portal hypertension because of its capacity to reduce portal pressure. In contrast to vasoconstrictors, isosorbide-5-mononitrate acts primarily by decreasing portal-collateral resistance without deleterious effects on liver function, although at high doses, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure may further decrease portal pressure. However, there is no information on the effects of isosorbide-5-mononitrate on variceal pressure, which is thought to be a major determinant of variceal haemorrhage.
We investigated the effects of isosorbide-5-mononitrate (40 mg, orally; n = 12) or placebo (n = 10) on variceal pressure (non-invasive endoscopic gauge) and hepatic haemodynamics in 22 patients with cirrhosis.
Placebo administration had no significant effects. In contrast, isosorbide-5-mononitrate significantly reduced variceal pressure (from 13.5 +/- 3.6 to 9.8 +/- 3.2 mmHg, p < 0.005). This was associated with a fall in wedged hepatic venous pressure (from 28 +/- 5.8 to 25.9 +/- 6.2 mmHg, p < 0.005), hepatic venous pressure gradient (from 20 +/- 4 to 18 +/- 4.7 mmHg, p < 0.005) and azygos blood flow (from 668 +/- 197 to 597 +/- 160 ml/min, p < 0.05), suggesting that the decrease in variceal pressure caused by isosorbide-5-mononitrate could be caused by both reductions in collateral resistance and collateral blood flow. Isosorbide-5-mononitrate moderately reduced mean arterial pressure (-13 +/- 16%; p < 0.005), its fall being directly related to the fall in hepatic venous pressure gradient (r = 0.6, p < 0.01).
The results of this study show that isosorbide-5-mononitrate markedly and significantly reduces variceal pressure in patients with cirrhosis and provide further support for its clinical use in the pharmacological treatment of portal hypertension.
5-单硝酸异山梨酯是一种长效硝基血管扩张剂，因其具有降低门静脉压力的能力而被用于治疗门静脉高压症。与血管收缩剂不同，5-单硝酸异山梨酯主要通过降低门静脉侧支循环阻力起作用，且对肝功能无有害影响，不过在高剂量时，动脉压下降引发的内脏反射性血管收缩可能会进一步降低门静脉压力。然而，关于5-单硝酸异山梨酯对静脉曲张压力影响的信息却尚无报道，而静脉曲张压力被认为是静脉曲张出血的主要决定因素。
我们研究了5-单硝酸异山梨酯（40毫克，口服；n = 12）或安慰剂（n = 10）对22例肝硬化患者的静脉曲张压力（非侵入性内镜测量）和肝脏血流动力学的影响。
给予安慰剂无显著效果。相比之下，5-单硝酸异山梨酯显著降低了静脉曲张压力（从13.5±3.6降至9.8±3.2 mmHg，p < 0.005）。这与肝静脉楔压下降（从28±5.8降至25.9±6.2 mmHg，p < 0.005）、肝静脉压力梯度下降（从20±4降至18±4.7 mmHg，p < 0.005）以及奇静脉血流量下降（从668±197降至597±160 ml/min，p < 0.05）相关，这表明5-单硝酸异山梨酯导致的静脉曲张压力降低可能是由侧支循环阻力和侧支循环血流量的减少共同引起的。5-单硝酸异山梨酯使平均动脉压适度降低（-13±16%；p < 0.005），其下降与肝静脉压力梯度的下降直接相关（r = 0.6，p < 0.01）。
本研究结果表明，5-单硝酸异山梨酯可显著降低肝硬化患者的静脉曲张压力，并为其在门静脉高压症药物治疗中的临床应用提供了进一步支持。
