Hepatic function during prolonged isolated rat liver perfusion using a new miniaturized perfusion circuit

Area of Science:

• * Pharmacology and Toxicology
• * Physiology
• * Biomedical Engineering

Background:

• * Existing isolated rat liver perfusion circuits are often costly, complex, or cause hepatic trauma.
• * Extended perfusion times are limited by poor hepatic biocompatibility in current designs.

Purpose of the Study:

• * To describe a new miniaturized circuit for isolated rat liver perfusion.
• * To evaluate the circuit's ability to maintain physiological conditions for up to 6 hours.

Main Methods:

• * A novel, miniaturized perfusion circuit with a buoyant organ bath and membrane oxygenator was designed.
• * Male Sprague-Dawley rat livers were perfused ex vivo for 6 hours using diluted rat blood and Krebs-Henseleit buffer.
• * Hepatic function was assessed via perfusion parameters, bile production, oxygen uptake, substrate clearance, enzyme activity, and histology.

Main Results:

• * Stable perfusion pressure (8.7 ± 1.7 mmHg) and flow rate (1.92 ± 0.06 mL/min/g) were maintained.
• * Optimal bile volume production (784 ± 84 µL/h) and hepatic oxygen uptake (0.99 µmol/L/min/g) were observed.
• * Minimal erythrocyte damage was indicated by a slight hematocrit decrease and controlled plasma free hemoglobin increase.

Conclusions:

• * The new miniaturized circuit effectively supports isolated perfused rat livers for 6 hours.
• * The system maintains near-physiological conditions, suitable for toxicological investigations.
• * Bile production, hepatic oxygen uptake, and plasma free hemoglobin levels are sensitive indicators of liver function in this model.