NONADHESIVE LIQUID EMBOLIC AGENT FOR CEREBRAL ARTERIOVENOUS-MALFORMATIONS - PRELIMINARY HISTOPATHOLOGICAL STUDIES IN SWINE RETE-MIRABILE

OBJECTIVE: To assess acute and chronic histopathological changes obser ved in a swine arteriovenous malformation model after endovascular del ivery of Embolyx E (Micro Therapeutics Inc., San Clemente, CA) and its organic solvent dimethyl sulfoxide (DMSO). To develop standard endova scular delivery techniques of Embolyx through microcatheters into swin e rete mirabile (RMB). METHODS: Forty RMBs in 22 swine were used to an alyze acute and chronic angiographic and histological changes after su perselective delivery of Embolyx E and/or its organic solvent (DMSO). Four RMBs (two for DMSO and two for Embolyx E study) were used as cont rol specimens. Angiographic and histological evaluations were obtained 18 days, 1 month, 3 months, and 6 months after the procedure. Particu lar attention was paid to the presence of focal or diffuse angionecros is, arterial revascularization, and perivascular inflammatory response . RESULTS: Staged and/or continuous delivery of Embolyx E were perform ed through the DMSO-compatible microcatheters without untoward cathete r ''gluing.'' All subacute/chronic specimens embolized with Embolyx E showed no evidence of angiographic recanalization. Twelve RMBs were us ed in acute studies, and all specimens showed no evidence of angionecr osis or aggressive inflammatory reaction. Subacute and chronic (total, n = 14) histological examinations of the RMBs showed mild inflammator y response manifested by monocellular infiltration and scattered forei gn body giant cell reaction. In the 9 of 14 subacute and chronic speci mens, focal disruption of elastica was observed along with embolic mat erials. Fourteen RMBs in eight swine were used to determine the safety range for DMSO injection. Two RMBs were used as control specimens. Ra pid intra-arterial delivery (0.5 ml/5-15 s, n = 6) of DMSO caused angi ographic vasospasm and histological endothelial necrosis. Slow injecti on (0.5 ml/30-120 s, n = 8) of DMSO showed minimum or no angiographic vasospasm, minimal adventitial inflammatory response, and no clinical complications. CONCLUSION: Embolyx E, an occlusive and nonadhesive emb olic agent, is capable of producing permanent occlusion of swine RMB w ith the development of mild intra- and perivascular inflammatory chang es and no clinical complications. The slow endovascular delivery of DM SO produces no untoward angiographic, pathological, or clinical change s. A fast injection of DMSO causes endothelial necrosis and severe inf lammatory response in the arterial wall. This embolic material seems t o have appropriate biochemical, anatomic, and histopathological charac teristics to be used in the treatment of cerebral arteriovenous malfor mations or vascular cranial base tumors.