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The Effects of Levovist and DD‐723 in Activating Platelets and Damaging Hepatic Cells of Rats
Author(s) -
Shigeta Kouichirou,
Itoh Kouichi,
Ookawara Shigeo,
Taniguchi Nobuyuki,
Omoto Kiyoka
Publication year - 2005
Publication title -
journal of ultrasound in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 91
eISSN - 1550-9613
pISSN - 0278-4297
DOI - 10.7863/jum.2005.24.7.967
Subject(s) - medicine , platelet , ultrasound , platelet activation , blood flow , nuclear medicine , pathology , contrast (vision) , radiology , artificial intelligence , computer science
Objective The purpose of this study was to compare platelet activation and hepatic cell damage produced by 2 ultrasonographic contrast agents with flow cytometric and ultrastructural analysis. Methods Suspension samples were made by mixing Levovist (SH U508A; Schering AG, Berlin, Germany) or DD‐723 (Nycomed; Amersham Health, Princeton, NJ) with whole blood. The final concentrations of Levovist in citrated whole blood were 0, 15, and 75 mg/mL, and those of DD‐723 were 0, 5, and 50 μL/mL. After exposure to ultrasound in vitro, flow cytometric analysis was performed to determine the concentration of the CD62P activation‐specific antigen. To compare the hepatic cell damage associated with these 2 agents, we divided 15 rats into 5 groups as follows: group 1, sham operation; group 2, Levovist injection only; group 3, DD‐723 injection only; group 4, Levovist injection (contrast agent) and ultrasound exposure; and group 5, DD‐723 injection and ultrasound exposure. The ultrasonographic contrast agents Levovist and DD‐723 were administered through the femoral vein and sonicated continuously for the first minute; this was followed by sweeping for 5 minutes 10 seconds after the contrast agent was injected. The rats were perfused via the heart with a fixative solution immediately after the sweeping, and then the liver was excised; the specimens were studied with electron and light microscopy. Results The percentage of CD62P‐expressing platelets increased in both contrast agent‐ultrasound exposure groups, and the percentage of CD62P‐expressing platelets was greater in the Levovist group. We observed vacuolation and round deposits in the hepatocytes in both contrast agent‐ultrasound exposure groups. Microbubbles were observed in the rat Kupffer cells, and a few hepatocytes were seen unexpectedly in the DD‐723 group but were found in neither the Kupffer cells nor the hepatocytes in the Levovist group. Conclusions Both contrast agents, Levovist and DD‐723, produced platelet activation and structural change in the rat hepatic cells, but only the microbubbles of DD‐723 were taken up by the Kupffer cells and a few hepatocytes.