Shigeta Kouichirou, Itoh Kouichi, Ookawara Shigeo, Taniguchi Nobuyuki, Omoto Kiyoka
Department of Clinical Laboratory Medicine, Jichi Medial School, Kawachi-gun, Tochigi-ken 329-0498, Japan.
J Ultrasound Med. 2005 Jul;24(7):967-74. doi: 10.7863/jum.2005.24.7.967.
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.
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 microL/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.
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.
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.
本研究旨在通过流式细胞术和超微结构分析比较两种超声造影剂所产生的血小板活化和肝细胞损伤情况。
将声诺维（SH U508A；德国先灵公司，柏林）或DD - 723（耐科明公司；安迈盛医疗，新泽西州普林斯顿）与全血混合制成悬浮样本。枸橼酸化全血中声诺维的终浓度分别为0、15和75 mg/mL，DD - 723的终浓度分别为0、5和50 μL/mL。体外超声照射后，进行流式细胞术分析以测定CD62P活化特异性抗原的浓度。为比较与这两种造影剂相关的肝细胞损伤，我们将15只大鼠分为5组如下：第1组，假手术；第2组，仅注射声诺维；第3组，仅注射DD - 723；第4组，注射声诺维（造影剂）并进行超声照射；第5组，注射DD - 723并进行超声照射。超声造影剂声诺维和DD - 723经股静脉给药，在第1分钟持续进行超声处理；在注射造影剂10秒后接着扫描5分钟。扫描结束后立即经心脏用固定液灌注大鼠，然后切除肝脏；对标本进行电子显微镜和光学显微镜检查。
在两种造影剂 - 超声照射组中，表达CD62P的血小板百分比均增加，且声诺维组中表达CD62P的血小板百分比更高。在两种造影剂 - 超声照射组的肝细胞中均观察到空泡形成和圆形沉积物。在大鼠枯否细胞中观察到微泡，在DD - 723组中意外地在一些肝细胞中也发现了微泡，但在声诺维组的枯否细胞和肝细胞中均未发现。
声诺维和DD - 723这两种造影剂均能引起大鼠肝细胞的血小板活化和结构改变，但只有DD - 723的微泡被枯否细胞和一些肝细胞摄取。
