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

Abstract

Cirrhosis is the common end stage of any given chronic liver disease, developing after persistent destruction and regeneration of parenchymal liver cells. The associated architectural distortion increases the intrahepatic vascular resistance, leading to portal hypertension and systemic circulatory disorders. This study investigates the impact of the changing vascular resistances on the hepatic and global circulation hemodynamics during cirrhogenesis. Cirrhogenesis was revisited using the thioacetamide rat model (N = 20). Rats were sacrificed at weeks 0, 6, 12, and 18. For each time-point, three-dimensional vascular geometries were created by combining hepatic vascular corrosion casting with μCT imaging. Morphological quantification of the trees branching topology provided the input for a lobe-specific lumped parameter model of the liver that was coupled to a closed-loop model of the entire circulation of the rat. Hemodynamics was simulated in physiological and pathological circumstances. The simulations showed the effect of the liver vascular resistances (driven by the hepatic venous resistance increase) on liver hemodynamics with portal hypertension observed after 12 weeks. The closed-loop model was further adapted to account for systemic circulatory compensation mechanisms and disorders frequently observed in cirrhosis and simulated their impact on the hepatic, systemic, and pulmonary hemodynamics. The simulations explain how vascular changes due to cirrhosis severely disrupt both hepatic and global hemodynamics. This study is a priori the first to model the rat's entire blood circulation during cirrhogenesis. Since it is able to simulate cirrhosis main characteristics, the model may be translated to humans for the assessment of liver interventions.