小剂量心得安加川芎嗪预防食管静脉曲张破裂出血的实验与临床研究

Low dose propranolol in combination with ligustrazine for prevention of recurrent esophageal varices bleeding: a randomly controlled experimental and clinical study

目的 探讨小剂量心得安与川芎嗪联用预防肝硬变食管静脉曲张破裂出血(EVB)复发的疗效、副反应及其作用机制。 方法 在用药前后采用血管插管法对8只肝硬变犬血流动力学指标进行检测。在临床上对治疗组(n=38,po心得安10mg+川芎嗪50mg,3次/d)和安慰剂组(n=36,服维生素B_110mg+维生素PP 50mg,3次/d)进行前瞻性对照研究,随访2a,并用彩色多普勒超声仪监测其门脉系统血流动力学变化。 结果 小剂量心得安与川芎嗪联用可使肝硬变犬WHVP,HVPG,Rpv及Ppv明显降低,对HR,MAP无明显影响。用药4wk后治疗组患者Qpv,Qsv,Dpv,Dsv及Qaz均显著下降(分别为1439±494 vs 1152±387,948±436 vs 529±362,1.43±0.25 vs 1.36±0.28,1.20±0.24 vs 0.85±0.16,0.94±1.18vs 0.71±1.04,P<0.05/0.01);随访2a,安慰剂组再出血率和死亡率均显著高于治疗组(P<0.05);临床上未见明显副作用。 结论 小剂量心得安与川芎嗪联用预防EVB复发是安全有效的。

AIM To assess the efficacy of low dose propranolol in combination with ligustrazine for the prevention of reurrent esophageal varices bleeding in liver cirrhosis, and its mechanism.METHODS By detecting portal pressure of experimental liver cirrhotic dogs (n=8) directly and measuring portal system flow in patients with portal hypertension and esophageal varices by color Doppler flow imaging, the therapeutic efficacy and safety of the therapy were investigated. Two comparable groups of 38 and 36 cases were used (taking propranolol 10 mg plus ligustrazine 50 mg or vitamin B1 10 mg plus vitamin pp 50 mg three times a day, respectively).RESULTS After oral administration of the drugs, the wedge hepatic venous pressure, hepatic venous pressure gradient, portal venous resistance and portal venous pressure of the liver cirrhotic dogs remarkebly reduced (P<0.05 0.01), and reached the lowest point at 60min, but the heart rate, and mean arterial pressure were not affected. Four weeks after administration of the drugs, the flow of portal vein, splenic vein and azygos, the diameter of portal vein and splenic vein in the treatment group were significantly decreased (1439±494 vs 1152± 387, 948±436 vs 529±362, 1.43±0.25 vs 1.36±0.28, 1.20±0.24 vs 0.94±0.19, 0.94±0.18 vs 0.71±0.04, respectively, P<0.05-0.01). No adverse effect was observed on the system circulation and the liver function. In the two years follow-up period, the bleeding rate and mortality rate of the placebo group were higher than that in the treatment groups (P<0.05), but those of the patients with liver cirrhosis grade C in the two groups had no significant difference (P>0.05). CONCLUSION Low dose propranolol plus ligustrazine is a safe and effective therapy for the prevention of recurrent esophageal varices bleeding, and worthy of further trial.