Effects of a mixture of a low concentration of n-butylcyanoacrylate and ethiodol on tissue reactions and the permanence of arterial occlusion after embolization

OBJECTIVE: Cyanoacrylates are the most commonly used liquid embolic agents. For embolization of arteriovenous malformations, a mixture of a low concentration of n-butylcyanoacrylate (NBCA) and Ethiodol (Savage Laboratories, Melville, NY) has been recommended for deeper penetration of the nidus. Dilution of NBCA, however, might result in different degrees of tissue reaction and might influence the permanence of vessel occlusion, with an increased risk of vessel recanalization. We compared tissue reactions induced by different NBCA/Ethiodol mixtures and analyzed the permanence of their embolic effects. METHODS: NBCA was diluted with Ethiodol to prepare the following standard solutions: Mixture A, low concentration (NBCA/Ethiodol ratio of 20:80); Mixture B, high concentration (50:50). The study was designed in two parts, because tissue reactions after embolization are considered to be a combination of foreign body reactions to solidified material and reactions to the injured blood vessel. Foreign body reactions were studied by intramuscularly injecting both glue mixtures into the backs of 18 rats. Specimens were obtained at various times after implantation. Immunohistochemical analysis and esterase staining were used to detect macrophages and neutrophils, respectively. The densities of these inflammatory cells were calculated and statistically compared. To study the degree of vascular wall injury and the permanence of embolic effects, the renal arteries in 48 rabbits were embolized with NBCA Mixture A or B. Six specimens for each group were obtained at various times after embolization. RESULTS: There was no significant difference in foreign body reactions between groups treated with Mixtures A and B, at any time. However, the macrophage density was larger for both groups at 3 months versus 3 days and for the group treated with Mixture B at 3 months versus 2 weeks. There was no difference in the degree of vessel wall injury. None of the embolized vessels demonstrated evidence of recanalization. CONCLUSION: The low concentration of NBCA induced a tissue response similar to that of the high-concentration form. Embolized vessels exhibited no greater incidence of recanalization. Therefore, embolization of arteriovenous malformations with diluted NBCA may be safe.