A Comprehensive Rat Model For Assessing Hepatic Transport Pathways Through Simultaneous Lymphatic And Blood Vascular...

The liver is a central metabolic and immunologic hub that processes nutrients, xenobiotics, and circulating immune mediators. Substances reach the hepatocytes and other hepatic cells via the sinusoidal capillaries that receive blood from the intestine via the portal vein and from the systemic circulation via the hepatic artery. Plasma filtrate from the sinusoidal capillaries drains into the space of Disse, where it can undergo metabolic transformation, participate in immune surveillance, or flow into lymphatic vessels to form hepatic lymph. Sampling of hepatic lymph and blood can help enable detailed analysis of hepatic transport, metabolic processes, and immune activity. A surgical rat model allowing simultaneous sampling of hepatic lymph outflow and systemic blood through three distinct cannulation sites is described: hepatic lymph duct, carotid artery, and jugular vein. Hepatic lymph and arterial cannulations enable continuous sampling, whereas the jugular vein cannula can be used for continuous hydration and fluid support or for venous blood collection, allowing comparison between arterial and venous blood. Successful cannulation yields hepatic lymph flow rates of approximately 0.1 mL/h in anesthetized rats, enabling continuous lymph sampling of up to 8 hours while simultaneous arterial and venous blood sampling is performed. This setup allows direct comparison between systemic arterial blood and hepatic lymphatic outflow, enabling comprehensive examination of hepatic transport and clearance, as well as metabolic and immune signaling processes. To further extend the model, terminal sampling of the hepatic artery and portal vein can be performed at the end of the procedure to enable direct comparison of hepatic inflow, outflow, and lymphatic drainage. Ultimately, these techniques provide a versatile platform for evaluating hepatic processes, including drug pharmacokinetics, nutrient flux and metabolism, and liver-specific responses, under various pathophysiological conditions.