Comparison of the Toxicities of Ethylene Vinyl Alcohol Copolymer (EVOH) preparations, Dimethyl Sulphoxide and N-Butyl 2-Cyanoacrylate on Cerebral Parenchyma in an Experimental Rabbit Model
AbstractAim:Ethylene vinyl alcohol copolymer (EVOH), its organic solvent dimethyl sulfoxide (DMSO) and N-Butyl 2-Cyanoacrylate (NBCA) are widely used in neurovascular embolization procedures and yet with potential risk of cytotoxicity. The aim of this study was to evaluate the toxic effect of EVOH-DMSO, its solvent DMSO and NBCA on cerebral parenchyma in a rabbit model.
Material and Methods:Forty-eight albino male rabbits were divided into 6 groups based on the substance injected into the parenchyma; normal saline, DMSO, NBCA, 6% EVOH-DMSO and 20% EVOH-DMSO and control group. At 72 hours the subjects were sacrificed and brain samples were harvested for histopathological examination and lipid peroxidase measurements.
Results:Neuronal degeneration and inflammatory reaction in the brain parenchyma was prominent especially in DMSO group and EVOH-DMSO groups. Furthermore, in EVOH group, extent of degeneration and inflammatory reaction was related to the concentration of the embolic agent. Lipid peroxidase activity was significantly increased in NBCA group as compared to all but to 20 % EVOH-DMSO group.
ConclusIon:EVOH and its solvent DMSO cause degeneration and inflammatory reaction in brain parenchyma and for EVOH this reaction was appeared to be dose dependent.
Keywords:Cerebral parenchyma, Cerebrovascular diseases, Embolization, Siyanoakrilat, Ethylene vinyl alcohol copolymer (EVOH), DMSO, Toxicity.
IntroductionThe endovascular management of arteriovenous malformations (AVM) dates back to 1960s, when Luessenhop first described angiographic treatment of AVMs by using plastic or steel materials as embolizing agents (13). Today, the selection of embolizing agent is quite challenging as the number of alternatives increased through years (2). Ethylene Vinyl Alcohol Copolymer (EVOH) and N-Butyl 2-Cyanoacrylate (NBCA) were mainly used for embolization procedures (slow vs. rapid embolizing agents, respectively) former one being more preferred after year 2000 (8,21).The management of AVMs and aneurysms by endovascular techniques is not free of complications. The rate of technical and embolization related complications have been reported being 6% and 12%, respectively. The technical complications included the micro-catheter entrapment and peripheral vessel perforations, whilst, embolization induced hemorrhage was reported in 4-16% of the cases, leading to disabilities or even death (10, 22). There are some previous studies regarding leakage of EVOH-DMSO into subarachnoid space (2). Acute subarachnoid hemorrhage, low grade microglial encephalitis, inflammatory cell infiltrations, necrosis and perivascular lymphocytes accumulations were among reported complications (3). There are also some reports for the angiotoxic and neurotoxic effects of the solvent DMSO and NBCA. Bakar et al have studied the effects of embolizing agents, leaking into subarachnoid space and calling attention to the paucity of data in the medical literature about toxic effects of embolizing agents and its components on brain tissue (2).This study aimed at demonstrating histological and biochemical effects of widely used embolizing agents and its components; NBCA, EVOH and DMSO upon contacting with neural parenchyma.
