title: Air-filled ultrasound contrast agents do not damage the cerebral microvasculature or brain tissue in rats.
abstract: OBJECTIVE
  Air microemboli may damage the cerebral microvasculature. The aim of this study was to evaluate the safety of ultrasound contrast agents composed of air microspheres with regard to cerebral damage when administered into the arterial system (ie, when not filtered by the capillary system of the lungs).
  
  
  METHODS
  Three experimental methods were used in 75 rats after injection of either Albunex, Echovist, or Levovist into the left heart ventricle. The alkaline phosphatase (ALP) method to demonstrate small segmental brain capillary and arteriolar dilatations (SCADs), intravenous injections of Evans blue and fluorescence microscopy to detect increased vascular permeability (blood-brain barrier damage), and histologic examination of the brain to detect microinfarction. Intracardiac injections of saline, air, and corn oil were used as controls.
  
  
  RESULTS
  Brain microinfarcts and SCADs formation of the brain microvasculature occurred only after control injections with corn oil. None of the brains from animals that received ultrasound contrast agent showed gross discoloration, as an indication of increased vascular permeability, with the Evans blue/fluorescence microscopy method. Definite leakage of Evans blue occurred only after large doses (150 microL) of air.
  
  
  CONCLUSIONS
  This study indicates that ultrasound contrast media composed of air microspheres do not cause lesions of the brain microvasculature or parenchyma.
authors.affiliation: Department of Neurology, The National Hospital, University of Oslo, Norway. n.k.j.haggag@klinmed.uio.no
authors.forename: K J
authors.initials: KJ
authors.lastname: Haggag
authors.forename: D
authors.initials: D
authors.lastname: Russell
authors.forename: P
authors.initials: P
authors.lastname: Walday
authors.forename: A
authors.initials: A
authors.lastname: Skiphamn
authors.forename: A
authors.initials: A
authors.lastname: Torvik
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002544:Cerebral Infarction / Q000209:etiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003287:Contrast Media / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018608:Ultrasonography, Doppler; D014664:Vasodilation
chemical_list: D000418:Albumins; C060687:Albunex; D003287:Contrast Media; D011134:Polysaccharides; C059891:SHU 508; C040642:SHU 454