Intraportal infusion of 99mtechnetium-macro-aggregrated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes.
BACKGROUND
Partial correction of metabolic liver disease by hepatocyte transplantation requires infusion of a large number of cells into the portal vein. Uncontrolled infusion of cells leads to extrahepatic shunting. Obstruction of the sinusoidal space may result in hemodynamic changes and impairment of liver function.


METHODS
Catheters connected to a port were placed into the caudal mesenteric vein of rabbits. After injection of 99mtechnetium-macroaggregated albumin (99mTc-MAA) surrogates or 99mTc-MAA/hepatocyte (Hc) mixtures (1:125), shunting into the lung was scintigraphically monitored. Volume flow (mL/min) and maximum velocity of the portal vein were recorded by color-coded Doppler ultrasound during intraportal application of 2.5 x 10(7) MAA particles, 2.5 x 10(7) isolated hepatocytes, and saline solution without particles or cells.


RESULTS
99mTc-MAA particles (2.5 x 10(7)) or equivalent MAA/Hc mixtures were completely retained in the liver. With additional application of 2.5 x 10(7) particles, shunting into the lung was observed in two animals of the MAA group. All animals in the hepatocyte group have received 5 x 10(7) MAA/Hc mixtures, and three of these received 10(8) mixtures without shunting. Maximum velocity and volume flow increased with saline infusion. Hepatocyte suspended in the same volume blunted the increase observed in the control group, but parameters remained normal. Liver enzymes increased after hepatocyte application but returned to normal values within 5 days.


CONCLUSIONS
Sinusoidal uptake capacity for hepatocyte or MAA particles varies at a wide range in normal rabbits. Scintigraphic monitoring of transplanted cells allows efficient monitoring of cell translocation into the lungs. No significant impairments of portal hemodynamics and liver function were detected.
Schneider
Andrea
A
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Attaran
Masoumeh
M
Gratz
Klaus F
KF
Bleck
Joerg S
JS
Winkler
Michael
M
Manns
Michael P
MP
Ott
Michael
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D002408:Catheters, Indwelling; D005969:Glutamate Dehydrogenase / Q000097:blood; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D006975:Hypertension, Portal / Q000000981:diagnostic imaging / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008102:Liver Circulation; D008642:Mesenteric Veins / Q000502:physiology; D011169:Portal Vein / Q000502:physiology; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics; D018615:Ultrasonography, Doppler, Color
D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase