BIOARTIFICIAL LIVER WITH WHOLE BLOOD PERFUSION

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Excerpt

Various bioartificial livers (BAL) have been developed as a treatment for patients with a severe liver failure. Most of these devices are perfused with patient's plasma. Therefore, a removal rate of toxins is limited by a slow plasma separation rate, and the systems become too complicated. For these reasons, we have initiated a series of studies to develop a simple system, through which whole blood can be perfused as in a hemodialysis therapy. A BAL reactor was prepared by inoculation of hepatocyte suspension into the inner space of the hollow fibers.
For in vitro study, human whole blood anti-coagulated with heparin was perfused through our system. Lidocaine was loaded to blood three times at 0, 24 and 48 h after BAL preparation. Metabolic activity for lidocaine was maintained for 48 h. The hepatocytes in the hollow fibers have been morphologically investigated by HE and immunohistochemical staining. We could conclude that porcine hepatocytes in the hollow fibers were not damaged during 48-hour perfusion.
The in vivo assessment of the BAL cartridge was done using a canine model. Canine whole blood was perfused through a hollow fiber cartridge without porcine hepatocytes for 24 h. The activated clotting time was controlled by low-molecular-weight heparin. Any significant thrombogenesis and hemolysis that could affect the BAL system and the canine were not observed. From these results, we concluded that our BAL is a promising liver assist device through which patient's whole blood can be perfused.
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