ProNectin F-grafted-ethylene vinyl alcohol copolymer (EVAL) as a liquid type material for treating cerebral aneurysm--an in vivo and in vitro study.

The authors aimed to develop a liquid material for embolization of aneurysms. In vitro and in vivo performances of the new embolic material were examined by cell culture and using an aneurysm model made in common carotid arteries (CCAs) of adult rats. Engineered protein ProNectin F (PnF), which contains 13 sites of an arginine-glycine-aspartic acid (RGD), was grafted onto ethylene vinyl alcohol copolymer (EVAL-g-PnF). The liquid material, EVAL-g-PnF dissolved in DMSO, was infused into an aneurysm model. The blood segments were harvested 2, 5, and 14 days and examined histologically. A number of bovine coronary artery endothelial cells became able to attach to and form cobblestone-like islands on the EVAL by incorporating PnF. The aneurysm model infused with the EVAL-g-PnF solution revealed that the aneurysm lumen was filled with proliferated fibroblasts and macrophages. On the other hand, the aneurysm model treated with unmodified EVAL showed that the cavity was almost filled with EVAL mass and that fibroblasts and macrophages filled a narrow space between the EVAL mass and the cavity wall. The results indicate that EVAL-g-PnF could be more suitable for reorganizing the cavity of an aneurysm than native EVAL.

Solidifying liquid with novel initiation system for detachable balloon catheters.

In endovascular surgery, to permanently hinder blood inflow into an aneurysm for example, a catheter is percutaneously introduced into an artery and the balloon is positioned and inflated by a solidifying liquid and then released into the diseased part. A novel solidifying liquid for the inflated balloon curable under the continuous feeding of oxygen through the wall of the balloon is described here. Glucose oxidase which oxidizes glucose producing hydrogen peroxide was used for polymerization of the solidifying liquid. This solidifying liquid cured even in the presence of oxygen and water. It was radiopaque when mixed with the iodinated X-ray contrast chemical iopamidol. In addition, the solidified liquid had appropriate mechanical properties. The endovascular surgery could be carried out safely using it.

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery.

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.

Characteristics of ethylene vinyl alcohol copolymer (EVAL) mixtures.

PURPOSE: To determine physical characteristics of mixtures of ethylene vinyl alcohol copolymer (EVAL) and metrizamide dissolved in dimethyl sulfoxide, liquid materials developed for embolization of arteriovenous malformations. METHODS: EVAL and dimethyl sulfoxide were mixed in various proportions and sterilized. The viscosity and density of each mixture was measured. Precipitation times were determined by dropping the mixtures into saline or human blood. The mixtures were filtered and the filtrates weighed. RESULTS: Densities and viscosities of the various mixtures differed significantly, proportionally to the concentration of EVAL. Precipitation times also differed significantly, in inverse proportion to the concentration of EVAL. Temperature and aqueous solution did not affect precipitation times significantly. The weight of the filtrate significantly increased with time but was constant for each precipitation time. Temperature significantly affected filtrate weight; aqueous solution did not. CONCLUSIONS: Because of their different physical properties, the various EVAL mixtures are suited to embolizing different types of arteriovenous malformations.

A new liquid material for embolization of arteriovenous malformations.

We have developed a liquid material for embolization of arteriovenous malformations that is a mixture of ethylene vinyl alcohol copolymer and metrizamide dissolved in dimethyl sulfoxide. Upon contact with blood, dimethyl sulfoxide rapidly diffuses into the blood and forms an ethylene vinyl alcohol copolymer elastic soft sponge that obstructs both the feeder and the nidus. The material, which is not adhesive, was used for embolization of three left cerebral arteriovenous malformations with satisfactory results.

Nonsuture microvascular anastomosis using an Nd-YAG laser and a water-soluble polyvinyl alcohol splint.

Anastomosis of rat common carotid artery was performed without sutures, using a neodymium (Nd)-YAG laser at 20 W for 100 msec; this power and exposure had been found optimal in preliminary experiments. An intraluminal intervascular splint made of water-soluble polyvinyl alcohol, which dissolved and disappeared within a few minutes after recirculation of blood, was used for precise "intima-to-intima" coaptation. No stay sutures or glue were required during the procedure. There was a 92% patency rate 24 hours after surgery, and the anastomosed vessels were still patent on the 7th and 30th postoperative days. Complications such as aneurysm formation or stenotic change were negligible. The fusion of the muscle layer and collagen fibers of the media in the anastomosis was confirmed histologically. A tensile strength test immediately following operation and 1 week later showed that this anastomosis was significantly better than that achieved with the usual manual suture method. The major advantages of this technique, combined with use of a water-soluble polyvinyl alcohol splint, are rapidity, consistency of results, and firm fusion with no residual foreign body.

Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases.

The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery.

Nonadhesive liquid embolic agent: role of its components in histologic changes in embolized arteries.

RATIONALE AND OBJECTIVES: The authors evaluated the safety and efficacy of a nonadhesive liquid embolic material and the role of its components in histologic changes in embolized arteries. MATERIALS AND METHODS: A Eudragit-E mixture (Rohm Chemische Fabrik, Darmstadt, Germany) was made of a cationic copolymer (Eudragit-E) dissolved in an equal volume of absolute ethanol and iopamidol. The Eudragit-E mixture, an ethanol-iopamidol mixture, and an iopamidol-saline mixture were injected into 12 rabbit renal arteries each. Three rabbits from each group were followed up for 1 day, 1 week, 1 month, and 3 months, at which time they were sacrificed. Kidneys were removed for histologic examination. RESULTS: The Eudragit-E mixture occluded all renal arteries without difficulty: the arteries did not recanalize. Histologically, acute vasculitis was caused by both the Eudragit-E and ethanol-iopamidol mixtures, but not by the iopamidol-saline mixture. Small infarctions were elicited with the ethanol-iopamidol mixture but not with the iopamidol-saline mixture. CONCLUSION: The Eudragit-E mixture is effective and easy to handle. Fifty percent ethanol may play a role in vessel occlusion with Eudragit-E mixture and in acute vasculitis.

Radiopaque solidifying liquids for releasable balloon technique: a technical note.

Recently we have reported a catheter having a balloon which can be released simply by twisting the catheter. In the technique, 2-hydroxyethylmethacrylate (HEMA) has been used as a solidifying liquid to prevent the released balloon from deflating. Since HEMA is not radiopaque, the place and the size of the balloon cannot be visualized under an X-ray image intensifier. The present investigation involves the preparation of a radiopaque, solidifying liquid, by mixing HEMA with a suitable contrast medium such as metrizamide, sodium iothalamate or meglumine sodium iodamide. The use of HEMA-contrast medium mixtures made injection of the solidifying liquids much more controllable.

[A midbrain arteriovenous malformation at quadrigeminal plate completely obliterated by embolization].

An eighteen year-old boy presented sudden loss of consciousness and tetraparesis. Radiological examinations revealed a ruptured midbrain arteriovenous malformation (AVM) at the right quadrigeminal plate. The patient recovered from symptoms by conservative treatment over 6 months with residual right hemisensory disturbance and mild diplopia during bilateral horizontal gaze. One year later, he was admitted to our institute for radical treatment of the AVM. On the angiography, the AVM was fed by two branches of the right long circumferential artery and a left paramedian penetrating artery of the posterior cerebral artery (PCA), and drained into the straight sinus via a dilated quadrigeminal vein. After much discussion on several strategies, endovascular surgery was chosen as a radical treatment. In the initial session, a medial branch of the right long circumferential artery was catheterized with Tracker-18, and embolized with 1.0 ml of ethylene vinyl alcohol copolymer (EVAL) without any deficits after negative provocative tests using Amytal and Xylocaine. Then, a lateral branch of the same artery was embolized with 0.8 ml of EVAL in the same way without any deficits. In the second session, catheterization into the left paramedian artery was difficult because of its small diameter and steep branching angle, and only a 3 mm hooked tip of Tracker-18 could be canulated into the feeding pedicle. Left oculomotor palsy was induced by provocative Xylocaine test. However, angiographic cure of the AVM was expected to be made possible by the occlusion of this pedicle, and the procedure was continued due to the request of the patient and his family.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nonsuture microvascular anastomosis--experimental arterial end-to-end anastomosis using plastic adhesive and a soluble PVA tube (author's transl)].

Microvascular anastomosis is now widely applied and many improved methods of the nonsuture anastomosis have been developed instead of the suture anastomosis for the purpose of saving time and making the reconstruction easier. We introduced a new nonsuture method of microvascular anastomosis using plastic adhesive and a soluble tube made of polyvinylalcohol (PVA). PVA, which had been utilized as a plasma expander, is a water-soluble polymer and its solubility is changeable depending on the degree of polimerization and percent saponification. We have made two kinds of soluble PVA tubes, the one has monolayer wall and the other double layered wall. The inner wall of the latter is more soluble than the outer wall. As plastic adhesives, we employed ethyl 2--cyanoacrylate, isopropyl 2--cyanoacrylate, and isobutyl 2--cyanoacrylate which were much superior to methyl 2--cyanoacrylate. Common carotid arteries of rats of 1.0 to 1.3 mm external diameter range were reconstructed and re-exploration was carried out at intervals of more than 7 days after operation. The anastomotic technique was very easy and it took about five minutes to reconstruct. In our last series, approximately 98 percent patency rate was achieved. The advantage of our method is that the blood stream is regained in the small soluble at the anastomotic site immediately after the release of hemostatic clamps.

[One-stage bilateral STA-MCA anastomosis in multiple occlusive cerebrovascular disease].

Out of 12 cases of bilateral stenosis of the internal carotid (IC) system underwent unilateral STA-MCA anastomosis on the symptomatic side, no ischemic signs recurred in 8 cases, while, in the remaining 4, symptoms appeared postoperatively, requiring the anastomosis of the contralateral side. Preoperative findings of CT scan, CAG and r-CBF were reviewed and compared. It has, consequently, become evident that, in the latter 4 cases, angiography showed stenotic lesion of over 50% of the ICA lumen, between the mastoid-mandibular line (MML) and the circle of Willis, on the initially asymptomatic side. Furthermore, in the same 4 cases, multiple thrombotic foci were more liable to be demonstrated on the CT scans and r-CBF was lowered in both hemispheres without significant difference in laterality. In additional 7 cases presenting such characteristics as stated above, one-stage bilateral STA-MCA anastomosis was carried out with a successful result.

A cationic polymer, Eudragit-E, as a new liquid embolic material for arteriovenous malformations.

We have developed a new liquid material for embolisation of arteriovenous malformations: a mixture of methyl and butyl methacrylate, plus dimethylaminoethyl methacrylate copolymer (Eudragit-E) in a solvent consisting of ethanol and iopamidol. Upon contact with aqueous substances, Eudragit-E precipitates rapidly and forms a soft elastic sponge within 3 s, as the ethanol diffuses. In blood, the positively charged Eudragit-E aggregates the negatively charged blood elements. Transcatheter embolisation of 4 canine and 52 rat renal arteries was feasible. Histological studies revealed no acute inflammatory reaction within 1 week, but mild to moderate reactions in the subacute and chronic stages. No recanalisation was seen. Because of its unique properties and excellent thrombogenicity the Eudragit-E, mixture seems a promising embolic material.

Experimental nonsuture microvascular anastomosis using a soluble PVA tube and plastic adhesive.

This article describes a new nonsuture method for microvascular anastomoses that uses plastic adhesives and soluble tube stents made of polyvinyl alcohol (PVA). Three soluble tubes were studied: one tube with a monolayered wall and two bilayered tubes of different thicknesses. The layers of the bilayered tubes consisted of PVA of different degrees of solubility. As plastic adhesives, ethyl 2-cyanoacrylate, isopropyl 2-cyanoacrylate, isobutyl 2-cyanoacrylate, and methyl 2-cyanoacrylate were employed; methyl 2-cyanoacrylate was by far the least effective. Anastomoses were performed on the common carotid artery of rats, and macroscopic, angiographic, and histologic investigations were carried out at intervals ranging from seven days to six months. The patency rates were 81% for the monolayered tube, and 92% and 98% for the bilayered tubes. The principal advantage of this method is that blood flow can be reestablished through the anastomosed site immediately after release of the hemostatic clamps.

Modified ethoxyethyl cyanoacrylate for therapeutic embolization of arteriovenous malformation.

Aiming at alleviating the problems of using 2-cyanoacrylates as a material for therapeutic embolization, this experiment made some physical modifications by mixing contrast media. It was found that the physicochemical properties of 2-cyanoacrylates can be altered by changing the concentration and the composition of the contrast media added. A 50 wt% cyanoacrylate-50 wt% contrast medium mixture has enough radiopacity for the practical requirement for embolization. A mixture of 50 wt% (ethoxyethyl cyanoacrylate-5 wt% lactide/epsilon-caprolactone copolymer), 25 wt% lipiodol and 25 wt% tetrafluorodibromoethane provides a viscosity of 13.8 cP, a bonding strength of 14.9 kg/cm2, a set time of 6 s, and a spreading in canine blood of 33 mm. It was concluded that the mixture is much more satisfactory than the conventional cyanoacrylates as an embolus material in vitro. The results obtained by in vivo experiments and clinical trials so far suggest that the mixture is very promising as a material for embolization.

New small-caliber antithrombotic vascular prosthesis: experimental study.

Vascular prostheses with the inner diameter smaller than 1 mm were implanted to the common carotid artery of rats, and their patency was examined. Four types of tubes were prepared for this purpose in Experiment 1: polyethylene (PE), poly-(acrylic acid)-grafted polyethylene (PE-AA), polyacrylamide-grafted polyethylene (PE-AAm), and poly(vinyl alcohol) (PVA) tubes. Comparative studies made using nonsuture anastomosis revealed that the PE-AAm and PVA tubes were antithrombotic, although disconnection was noted at the anastomotic sites within 1 week and 1 month, respectively. Thereafter in Experiment 2, the PVA tubes were implanted to the common carotid artery of 20 rats using conventional anastomosis. Neither anticoagulants nor fibrinolytic agents were used in both series of experiments. Patency of the PVA tubes was 80% after 1 week and 70% after 1 month. In patent cases after 1 month, the luminal surfaces of the prostheses and the host arteries were examined using scanning electron microscopy. The lumen of the arteries and anastomotic sites was covered with endothelial cells, while the lumen of the PVA tubes was free from thrombi and there was no neointima formation. So far, there has been reported no manmade material that has completely antithrombotic property in vivo. However, our studies disclosed that PVA is antithrombotic and one of the most promising materials for the inner surface of small vascular prostheses.

Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material.

A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3-0.7 microns in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments.

Blood compatibility of hydrophilic polymers.

Blood compatibility has been studied for hydrophilic polymers such as poly(vinyl alcohol) (PVA), its derivative, and polyethylene grafted with water-soluble monomers. The surfaces in contact with electrolyte solutions have been characterized by measuring the zeta potentials. The study of plasma protein adsorption on these polymers has revealed that bovine serum albumin as well as bovine serum fibrinogen adsorbs to a lesser extent as the hydrophilicity of the polymers increases. Platelet deposition and fibrin formation, examined using platelet-rich plasma, have been found to take place less significantly on PVA as well as sodium acrylate- and acrylamide-grafted polyethylene than on nongrafted and acrylic acid-grafted polyethylene. Ex vivo experiments with canine whole blood have shown that formation of thrombus on PVA is less than on siliconized glass but increases upon heat treatment which reduces the hydrophilicity. When PVA tubes of about 1 mm diameter are anastomosed to the carotid artery of rat, the patency rate is found to depend strongly on the anastomotic technique. From the results on the zeta potential and the experiments in vitro and ex vivo it can be concluded that the material having a surface from which solvated, neutral chains are extended into the outer aqueous phase may exhibit excellent resistance to thrombus formation.