Combis J M, Vinel J P, Badia P, Barange K, Payen J L, Combis F, Desmorat H, Pascal J P
Service d'hépato-gastroentérologie, CHU Purpan, Toulouse, France.
Br J Clin Pharmacol. 1996 May;41(5):409-13. doi: 10.1046/j.1365-2125.1996.03279.x.
Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.
普萘洛尔和吗多明均已被证明可降低肝硬化患者的肝静脉压力梯度。本研究旨在评估这两种药物联合使用对肝硬化患者内脏和全身血流动力学的影响。15例经活检证实为酒精性肝硬化的患者在基础状态下进行血流动力学测量,口服4 mg吗多明60分钟后,再静脉注射15 mg普萘洛尔15分钟后再次测量。与基线值相比,发现吗多明可降低平均动脉压(-7.9%,P<0.01)、心输出量(-7.3%,P<0.01)、肺楔压(-45.8%,P<0.05)和肝静脉压力梯度(-11.7%,P<0.01)。普萘洛尔可降低心率(-21%,P<0.01),进一步降低心输出量(-20.6%,P<0.01)和肝静脉压力梯度(-10.5%,P<0.01)。总体而言,吗多明加普萘洛尔可降低平均动脉压(-8%,P<0.01)、心率(-19%,P<0.01)、心输出量(-26.5%,P<0.01)和肝静脉压力梯度(-21%,P<0.01)。吗多明和普萘洛尔联合使用对肺楔压、肝血流量和吲哚菁绿的肝内在清除率无显著影响。我们得出结论,在肝硬化患者中,吗多明和普萘洛尔可增强它们对肝静脉压力梯度的作用。因此,这种联合用药可能对门静脉高压的治疗有用。