title: Influence of contrast ultrasonography with perflutren lipid microspheres on microvessel injury.
abstract: 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.
authors.affiliation: Department of Integrated Medicine 1, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Yasu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.forename: Nobuki
authors.initials: N
authors.lastname: Kudo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kuroki
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Muneyasu
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000000981:diagnostic imaging / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008863:Microspheres; D011134:Polysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects*; D014463:Ultrasonography / Q000009:adverse effects*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D011134:Polysaccharides; C059891:SHU 508; C042852:perflutren