Reichen J, Le M
J Clin Invest. 1986 Aug;78(2):448-55. doi: 10.1172/JCI112596.
The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multiple-indicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.
在肝硬化大鼠的灌注肝脏中研究了钙通道阻滞剂维拉帕米对微循环模式和肝功能的影响。通过多指示剂稀释技术测定,与对照组相比,肝硬化肝脏具有更高的血管阻力、增加的肝内分流、更小的血管外白蛋白间隙和更大的血管外蔗糖间隙。通过测定普萘洛尔和安替比林的摄取来评估肝功能,肝硬化肝脏中的肝功能明显降低。然后通过维拉帕米药理降低门静脉压力25%,或通过降低流入量流体动力学降低门静脉压力。维拉帕米使血管阻力降低22%。这与肝内分流减少38%和血管外白蛋白间隙增加62%相关。流体动力学降低压力没有效果或有不良影响。维拉帕米引起的微循环特征改善与氧消耗显著改善(+21%)和安替比林清除率显著改善(+20%)相关。我们得出结论,大鼠肝硬化的微血管扭曲可被维拉帕米等血管扩张剂部分逆转。