Increased sinusoidal volume and solute extraction during retrograde liver perfusion

Area of Science:

• Physiology
• Hepatology
• Hemodynamics

Background:

• Retrograde isolated liver perfusion is used to study liver function.
• Hemodynamic effects of retrograde flow are not well understood.
• Previous studies did not characterize hemodynamic differences between anterograde and retrograde perfusion.

Purpose of the Study:

• To characterize the hemodynamic effects of retrograde versus anterograde perfusion in isolated rat livers.
• To determine if hemodynamic differences explain altered compound extraction during retrograde perfusion.
• To investigate the impact of flow direction on hepatic extracellular space and sinusoidal morphology.

Main Methods:

• Measurement of hepatic extracellular space using [14C]sucrose washout and direct entrapment.
• Light microscopy and morphometry of perfusion-fixed livers.
• Comparison of perfusate flow dynamics during anterograde and retrograde perfusion.

Main Results:

• Retrograde perfusion resulted in a three- to fourfold increase in hepatic extracellular space.
• Light microscopy revealed marked sinusoidal distension during retrograde perfusion.
• Increased transit time and sinusoidal surface area were observed during retrograde flow.

Conclusions:

• Retrograde perfusion significantly alters liver hemodynamics by distending sinusoids.
• The presinusoidal level likely represents the maximum resistance to perfusate flow.
• Sinusoidal distension and increased transit time may enhance the extraction of compounds like 12-NBDS during retrograde perfusion.