Observation Of Alprostadil Combined With Propranolol In Patients With Cirrhosis And Portal Hypertension

ObjectiveCirrhosis is a chronic, progressive, diffuse inflammation and fibrosis of liver disease,caused by many reasons. The mainly manifest is decreased liver function and portal hypertension, the latter one is the main cause of esophageal-gastro varices(EGV),often induced to the death of the patients becase of hemorrhea; portal htpertension can also lead to intractable ascites, hypersplenism and other clinical manifestations, but now there is no satisfactory therapeutic measure. Beta blocker propranolol is believed to be the first choice drug for the treatment of portal hypertension, since 1980 after Lebrec used applied to reduce portal vein pressure. Propranolol can make the portal pressure drop by reducing cardiac output and visceral blood vessels, but only 1/3-1/2 of the patients can make HVPG dropped to 12 mm Hg or below, there are still 30% of the patients pulse pressure has no obvious decline in long-term use the drug. And because of sinus bradycardia, bronchial asthma patients exist taboos, so the single drug propranolol in the treatment of portal hypertension have limitations. In recent years, more and more scholars committed to the research of combination treatment of portal hypertension, and thus to minimize the side effects of propranolol and enhance curative effect, in order to achieve the purpose of better reduce portal vein pressure. Prostaglandin E1, as a kind of high efficient biological active substances has been widely used in the treatment of liver diseases, such as hepatorenal syndrome, intractable ascites of cirrhosis, liver transplantation, etc. In various liver diseases, and its protective liver cell, prevent liver cell necrosis, inhibiting liver fibrosis, improve local microcirculation, regulate immune function, etc. But at present for the front and propranolol combination in treatment of portal hypertension are rarely reported. This topic by color doppler ultrasound to monitor in the portal and splenic vein diameter measuring inner diameter and average blood flow velocity of the portal vein, splenic vein4diameter and average blood flow velocity, calculate out the venous blood flow and splenic venous blood flow, data statistics and analysis. Studying whether the combination is superior to the single drug, and its action mechanism. MethodWe selected 60 cases of patients with liver cirrhosis and portal hypertension, than randomly divided into control group and treatment group, control group 29 cases,treatment group 31 cases. The diagnosis of liver cirrhosis with the 2000 Xi’an sixth infectious disease academic conferences of the revised diagnostic criteria. All of the patients had no gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome and other complications, no or only a small amount of ascites; all of then were not for shunt, recently unused other vasoactive ordiuretics drugs. The general situation of the 2 groups of patients were similar, have no statistical significance and have comparability. The control group(propranolol group) treated with propranolol 10-20 mg orally, 3 times a day(about 25% to reduce heart rate as a standard),for 20d; Thetreatment group(alprostadil + propranolol group) received alprostadil 100 ug adding0.9% sodium chloride 100 ml, intravenous drip slowly, 1 times a day, concurrently received 10-20 mg propranolol orally, 3 times a day(about 25% to reduce heart rateas a standard) 20 d. The other conventional hepatoprotective drugs were alike. All the patients were measured the diameter(Dpv) and the mean blood flow velocity(Vpv) of portal vein,the diameter(Vsv)and the mean blood flow velocity(Vsv) of splenic vein, then calculated portal, splenic vein blood flow(Qpv, Qsv) respectively according to the formula of Q= π R2 ? V ? 60 before and after therapy, then statistical analysis data.Statistical analysis: the statistical analysis was performed using SPSS10.0 statistical software, the measurement data are mean standard deviation(X ± S), two groups were compared with the independent samples t test; P<0.05 test that all the differences had statistical significance. ResultThe portal and splenic vein diameter and average blood flow velocity, blood flow rate had no difference of the 2 groups before treatment(P > 0.5). The treatment group compared with control group, the medicine Dpv、Dsv、Vsv were decreased(P < 0.05), statistically significant; Vpv has no obvious change, no statistical significance; Qpv after treatment decreased, but without statistical significance; Qsv down significantly compared with control group, there was significant statistical significance(P < 0.01); Qsv/Qpv significantly decreased, with statistical significance(P < 0.05). Treatment group curative effect is better than that of control group, especially the spleen venous blood flow reduction is most obvious. ConclusionThe treatment effect of Alprostadil combined with propanolol is better than that of the single drug in liver cirrhosis. There are two theory of pathogenesis of liver cirrhosis, blood flow forward and flow backward. Propranolol can slow heart rate, decreased cardiac output, reduced blood flow in the portal, decrease the portal venous pressure by blocking β1 receptor, the drug is acting on the forward flow mechanism. Alprostadil treatment of liver cirrhosis with portal hypertension is the role of the backward flow mechanism: 1 Alprostadil can directly act on vascular smooth muscle, relaxation the portal venous, decreased the arterial pressure, then the sympathetic nerve excitability release large amounts of catecholamines, to contract the visceral vessels, decrease the blood flow of the portal vein, to lower the pressure; 2 to dilate the small vascular of the intrahepatic then reduce the resistance of the portal blood flow, the reduction of the portal venous hyperemia, thereby reducing the hepatic venous pressure gradient; 3 to increase the concentration of nitric oxide and prostaglandins in plasma, decrease the concentration of thromboxane, endothelin vasoconstriction substance; 4 eliminating endotoxin and inhibiting thrombosis; 5 Alprostadil has the effect of anti hepatic fibrosis. Alprostadil combined with propanolol can also act on "backward flow theory" and "forward flow theory", and the application of Alprostadil can reduce the effect of propranolol increased portal resistance, the interaction between the two can be reduced portal pressure and improve hepatic circulation. Because the sample number is small, short duration of follow up, large-scale clinical trials to be further confirmed.