H_2受体拮抗剂对门脉高压症门脉血液动力学影响的动物实验研究

Effects of cimetidine on portal hemodynamics in dogs with portalhypertension

目的探讨H2受体拮抗剂甲氰咪胍对肝硬化门脉高压症犬门脉血液动力学的影响。方法以胆总管结扎法成功制备胆汁性肝硬化门脉高压症模型犬11只,随机分为两组为甲氰咪胍组(n=7)、盐水对照组(n=4);另取4只正常犬为正常对照组。经股动脉、股静脉、右颈外静脉分别插管,以多导生理记录仪、电磁流量计等检测门脉及全身血液动力学变化,使用RF-3000型荧光分光光度计测量血浆组织胺浓度。结果甲氰咪胍组静脉注射甲氰咪胍5、15、306、0、90和120 min后,自由门脉压平均值均较注射前明显下降(Π<0.05),肝静脉楔入压、肝静脉压梯度、门静脉阻力均同步下降。肝动脉血流量无显著改变,门静脉血流量及全肝血流量轻度增多。肝静脉自由压、下腔静脉压、腹主动脉平均压及心率均无明显变化。自由门静脉压下降最大幅度与股静脉血血浆组织胺浓度呈显著正相关(p=0.7874,Π<0.05)。盐水对照组及正常对照组上述各指标均无显著变化。结论H2受体拮抗剂甲氰咪胍通过拮抗肝硬化门脉高压症犬血中异常升高的组织胺的作用,舒张肝血管床,降低门脉血流阻力,从而降低门脉压力,同时使门脉及全肝血流量轻度增加,而对全身血流动力学无不良影响。

Objective To investigate the effets of cimetidine on portal hemodynamics in dogs with cirrhosis and portal hypertension. Methods Cirrhosis and portal hypertension were successfully induced in eleven dogs. These dogs were then divided into：eimetidine group（ n = 7） and saline control group（ n = 4）, selected other 4 dogs for a monnal group. Phisiologieal polygraph, electromagnetic flowrneters and other devices were used to detect the changes of portal and systemic hemodynamies of the normal group and e.cimetidine group of portal hypertensive dogs after they were injected intravenously with cimetidine（0.012 g· kg^-1 weight） and of saline control group of portal hypertensive dogs after injection of normal saline. Results In cimetidine group, 5, 15, 30, 60, 90, and 120 minutes after eimetidine injection, free portal pressure decreased 5.2 % （ P 〈 0.05）, 14.1 （ P 〈 0.01 ）, 13.7 （ P 〈 0.01 ）, 12.9 % （ P 〈 O. 01）, 9.3 % （ P 〈 O. O1 ）, 6.5 （ P 〈 O. 05）, respectively. Wedged hepatic venous pressure, hepatic venous pressure gradient, portal venous resistance decreased synchronously. There was no significant change in hepatic arterial flow. Portal venous flow and total hepatic flow slightly increased. There was no significant change in free hepatic venous pressure, inferior vena cava pressure, mean aorta arterial pressure and heart rate. The maximum decreased values of free portal pressure were significantly positively correlated to the histamine concentrations of femoral vein blood（ r = 0.7874, P 〈 0.05）. No significant changes of any index mentioned above wre found in saline control group after injection of momal saline and in normal group. Conclusion Cimetidine can reduce portal pressure, because it can reduce portal venous resistance by antagonizing the action of histamine. Cimetidine can slightly increase portal venous flow and has no bad effects on systemic hemodynamics.