Experimental Study On Roles Of Stresses In The Pathogenesis And Development Of Portal Hypertension

Objective: Through establishing a rabbit model of pre-hepatic portal hypertension and determining the changes of biomechanical properties such as stress and strain of portal vein and small intestinal mesenteric vein, to discuss the effect of stress on the pathogenesis and development of portal hypertension and look for the probability of noninvasive method of measuring portal pressure..Methods: The pre-hepatic portal hypertension models are established in rabbits by total portal vein ligation (PVL) in two steps. CT angiography (CTA) of portal venous system is applied to the rabbits and 3D reconstruction of the portal venous system is made with special software to depicting the changes of portal venous system. Ultrasound technique is used in vitro before and after PVL so as to calculate the shear rate. The diameter and hemodynamic parameter such as pressure, blood flow of portal vein and small mesenteric vein are measured after PVL. The shear stress and circumferential stress of portal vein and small mesenteric vein are calculated, and the relations of shear stress and circumferential stress between the two veins are analyzed. Also, the correlationship of portal shear rate and portal pressure is analyzed to discuss their relation. The opening angle, axial and circumferential strain is measured and calculated by computer image analysis. The correlationship of pressure, shear stress and circumferential stress between portal vein and small mesenteric vein are analyzed. And the correlationship between shear stress and portal vein remodeling, circumferential stress and portal vein remodeling are also analyzed respectively. And so do in the small mesenteric vein. Statistical analysis was made by software SAS. Results: 1.After PVL, portal pressure increased significantly, blood flow to liver greatly decreased, and the diameter of portal vein became larger. Through CTA and 3D reconstruction software, different degrees of dilatation and distortion of the small intestinal mesenteric vein can be seen in PVL rabbits at different time after PVL, and the total rate of small intestinal mesenteric vein dilatation was 80%. 2. As compared with control group, the portal vein opening angle, circumferential strain in medium-grade group and heavy-grade group are significantly larger. In the same two groups, the opening angle and circumferential strain are also larger than that of control group. 3. In medium-grade and heavy-grade group, the shear stress of portal vein is significantly lower compared to control group, while circumferential stress is markedly higher. In all the three groups, the shear stress is lowered significantly while the circumferential stress is markedly higher. 4. In all the PVL rabbits, the opening angle, axial strain and circumferential strain of portal vein have linear correlation with that of small mesenteric vein, whose coefficient is 0.882, -0.726 and 0.525 respectively. So do the pressure, shear stress and circumferential stress, whose coefficient is 0.865, 0.593, 0.944 and 0.593 respectively. The shear rate got through ultrasound technique and the portal pressure measured through invasive method in normal rabbits have linear correlation, with coefficient r=-0.8182. while in PVL group, the linear correlation also exists, with r=-0.7422. Conclusions: 1. Pre-hepatic portal hypertension rabbit model can be successfully established by means of totally ligation of portal vein in two steps. 2. CTA can be used as a noninvasive method to display the portal venous system in portal hypertension. 3. The mechanical environment of portal vein and small intestinal mesenteric vein changed significantly in pre-hepatic portal hypertension, with lowered shear stress, increased pressure and circumferential stress. There is linear correlation between the shear stress and circumferential stress in the portal vein and small intestinal mesenteric vein. 4. In pre-hepatic portal hypertension, the biomechanical characteristics of portal vein and small intestinal mesenteric vein changed significantly, with increased opening angle and circumferential strain. 5. There is linear correlation between the shear rate got through ultrasound technique in vitro and portal pressure.