Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats

Area of Science:

• Cardiovascular Physiology
• Hepatology
• Medical Imaging and Modeling

Background:

• Cirrhosis represents the end stage of chronic liver disease, characterized by liver cell damage and regeneration.
• This process leads to architectural distortion, increasing intrahepatic vascular resistance and causing portal hypertension.
• Portal hypertension triggers systemic circulatory disorders, significantly impacting overall hemodynamics.

Purpose of the Study:

• To investigate the impact of changing vascular resistances on hepatic and global circulation during cirrhogenesis.
• To model the hemodynamic consequences of vascular alterations in the liver.
• To explore systemic circulatory compensation mechanisms and disorders in cirrhosis.

Main Methods:

• Utilized a thioacetamide rat model (N=20) with sacrifice at 0, 6, 12, and 18 weeks.
• Generated 3D vascular geometries via hepatic vascular corrosion casting and micro-CT imaging.
• Developed a lobe-specific lumped parameter liver model coupled to a closed-loop whole-body circulation model for hemodynamic simulations.

Main Results:

• Simulations demonstrated increased liver vascular resistances, particularly hepatic venous resistance, leading to portal hypertension by 12 weeks.
• The model simulated systemic circulatory compensation and disorders, analyzing their effects on hepatic, systemic, and pulmonary hemodynamics.
• Vascular changes inherent to cirrhosis were shown to severely disrupt both hepatic and global hemodynamics.

Conclusions:

• The developed model effectively simulates key hemodynamic characteristics of cirrhosis.
• Vascular remodeling in cirrhosis profoundly disrupts liver and systemic blood flow.
• This rat model offers a platform for human studies assessing liver interventions.