Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile.
OBJECTIVE
To assess acute and chronic histopathological changes observed in a swine arteriovenous malformation model after endovascular delivery of Embolyx E (Micro Therapeutics Inc., San Clemente, CA) and its organic solvent dimethyl sulfoxide (DMSO). To develop standard endovascular delivery techniques of Embolyx through microcatheters into swine rete mirabile (RMB).


METHODS
Forty RMBs in 22 swine were used to analyze acute and chronic angiographic and histological changes after superselective delivery of Embolyx E and/or its organic solvent (DMSO). Four RMBs (two for DMSO and two for Embolyx E study) were used as control specimens. Angiographic and histological evaluations were obtained 18 days, 1 month, 3 months, and 6 months after the procedure. Particular attention was paid to the presence of focal or diffuse angionecrosis, arterial revascularization, and perivascular inflammatory response.


RESULTS
Staged and/or continuous delivery of Embolyx E were performed through the DMSO-compatible microcatheters without untoward catheter "gluing." All subacute/chronic specimens embolized with Embolyx E showed no evidence of angiographic recanalization. Twelve RMBs were used in acute studies, and all specimens showed no evidence of angionecrosis or aggressive inflammatory reaction. Subacute and chronic (total, n = 14) histological examinations of the RMBs showed mild inflammatory response manifested by monocellular infiltration and scattered foreign body giant cell reaction. In the 9 of 14 subacute and chronic specimens, focal disruption of elastica was observed along with embolic materials. Fourteen RMBs in eight swine were used to determine the safety range for DMSO injection. Two RMBs were used as control specimens. Rapid intra-arterial delivery (0.5 ml/5-15 s, n = 6) of DMSO caused angiographic vasospasm and histological endothelial necrosis. Slow injection (0.5 ml/30-120 s, n = 8) of DMSO showed minimum or no angiographic vasospasm, minimal adventitial inflammatory response, and no clinical complications.


CONCLUSIONS
Embolyx E, an occlusive and nonadhesive embolic agent, is capable of producing permanent occlusion of swine RMB with the development of mild intra- and perivascular inflammatory changes and no clinical complications. The slow endovascular delivery of DMSO produces no untoward angiographic, pathological, or clinical changes. A fast injection of DMSO causes endothelial necrosis and severe inflammatory response in the arterial wall. This embolic material seems to have appropriate biochemical, anatomic, and histopathological characteristics to be used in the treatment of cerebral arteriovenous malformations or vascular cranial base tumors.
Murayama
Y
Y
Division of Interventional Neuroradiology, and Leo G. Rigler Radiological Research Center, University of California, Los Angeles, School of Medicine 90024, USA.
Viñuela
F
F
Ulhoa
A
A
Akiba
Y
Y
Duckwiler
G R
GR
Gobin
Y P
YP
Vinters
H V
HV
Greff
R J
RJ
D000818:Animals; D001672:Biocompatible Materials; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005030:Ethylenes / Q000627:therapeutic use* / Q000633:toxicity; D005549:Foreign-Body Reaction / Q000473:pathology; D002538:Intracranial Arteriovenous Malformations / Q000473:pathology / Q000628:therapy*; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000473:pathology; D014677:Pharmaceutical Vehicles; D011145:Polyvinyls / Q000627:therapeutic use* / Q000633:toxicity; D013552:Swine
D001672:Biocompatible Materials; D005030:Ethylenes; D014677:Pharmaceutical Vehicles; D011145:Polyvinyls; D004121:Dimethyl Sulfoxide