title: Acute and chronic swine rete arteriovenous malformation models: effect of ethiodol and glacial acetic acid on penetration, dispersion, and injection force of N-butyl 2-cyanoacrylate.
abstract: OBJECTIVE
  Liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). Currently, the most commonly used agent is N-butyl 2-cyanoacrylate (NBCA). Various NBCA mixtures, arterial hypotension, and Valsalva maneuver (increased positive end-expiratory pressure) during the injection of the acrylate have been used to address hemodynamic and architectural variations of an AVM; however, the precise in vivo polymerization, distribution, and kinetics of NBCA mixtures are unknown. We investigated the effect of different acrylate/Lipiodol mixtures and the addition of glacial acetic acid (GAA) on the penetration, dispersion, and injection force of NBCA.
  
  
  METHODS
  A swine rete AVM model that has been described elsewhere was used for the embolization. In one subgroup of animals, embolization was performed immediately after construction of the AVM model. In a second subgroup, a chronic AVM model was used. GAA was added to the NBCA mixture to decrease the pH value of the solution and prolong the polymerization time. The addition of GAA allowed us to reduce the amount of Lipiodol, thereby reducing the viscosity of the mixture. A total of 30 swine were used for both the acute (n = 23) and chronic (n = 7) subgroups. The following mixtures of Lipiodol/NBCA and GAA (% vol/%vol + microL) were used for embolization: 80/20 + 0; 50/50 + 0; 50/50 + 5; 50/50 + 10; and 50/50 + 20. A total of six retia per mixture were used for the analysis. Glue injection pressure profiles were recorded in each experiment. High-resolution radiographic images obtained from the harvested retia were used to correlate the dispersion and depth of glue penetration with the AVM hemodynamics. The effect of different amounts of GAA on the glue dispersion and depth of penetration of the mixtures was also studied.
  
  
  RESULTS
  Using the same pressure gradients, less viscous NBCA + GAA mixtures led to a deeper nidal penetration. The addition of 20 microL of GAA resulted in a three times higher penetration and dispersion of the NBCA mixture that was more homogenous.
  
  
  CONCLUSIONS
  The viscosity of the liquid embolic agent used is an important limiting factor for an AVM embolization. Reducing the amount of Lipiodol improves nidus penetration. Quicker polymerization can be overcome by adding GAA, which reduces the pH of the mixture.
authors.affiliation: Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Lieber
authors.forename: A K
authors.initials: AK
authors.lastname: Wakhloo
authors.forename: R
authors.initials: R
authors.lastname: Siekmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Gounis
mesh_terms: D019342:Acetic Acid / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004621:Embolization, Therapeutic / Q000379:methods*; D004659:Enbucrilate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004998:Ethiodized Oil / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007267:Injections; D002538:Intracranial Arteriovenous Malformations / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy*; D008297:Male; D011108:Polymers; D011859:Radiography; D013552:Swine; D014783:Viscosity
chemical_list: D004338:Drug Combinations; D011108:Polymers; D004998:Ethiodized Oil; D004659:Enbucrilate; D019342:Acetic Acid