Kobayashi Nobuhiko, Yasu Takanori, Yamada Satoshi, Kudo Nobuki, Kuroki Masatoshi, Miyatake Kunio, Kawakami Masanobu, Saito Muneyasu
Department of Integrated Medicine 1, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Circ J. 2003 Jul;67(7):630-6. doi: 10.1253/circj.67.630.
Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.
据报道，微泡可增强动物系统中与超声（US）相关的副作用。本研究调查了使用全氟丙烷脂质微球（一种最近开发的第二代造影剂）进行超声造影对微血管的影响。将大鼠肠系膜暴露于1.8MHz的脉冲超声下，静脉注射全氟丙烷（0.1或1.0ml/kg）或Levovist（300mg/kg），并检查微血管出血和内皮细胞损伤情况。通过碘化丙啶的荧光来识别受损的内皮细胞。还在大鼠心肌中检查了微血管出血情况。与假手术相比，0.1ml/kg的全氟丙烷与超声暴露之间的相互作用不会导致微血管出血，也不会增加内皮细胞损伤，除非出现频繁、强烈的超声暴露。当剂量增加到1.0ml/kg时，全氟丙烷与超声暴露的联合作用导致毛细血管出血，并增加了毛细血管和小静脉中的内皮细胞损伤（p<0.01）。然而，微血管出血和内皮细胞损伤的发生率并未超过使用Levovist微泡时的情况。在心肌中，在任何情况下均未观察到微血管出血。总之，全氟丙烷脂质微球在剂量为1.0ml/kg时与其他造影剂一样会增强与超声相关的微血管损伤，但在剂量为0.1ml/kg且超声设置适当时则不会。
