In Vivo Experimental Endovascular Uses of Cyanoacrylate in Non-Modified Arteries: A Systematic Review

Abstract

Cyanoacrylates were first used for medical purposes during World War II to close skin wounds. Over time, medical applications were developed, specifically in the vascular field. Uses now range from extravascular instillation in vascular grafting to intravascular injection for embolization. These applications were made possible by the conduct of numerous preclinical studies involving a variety of tests and outcome measures, including angiographic and histological criteria. Cyanoacrylates were first harshly criticized by vascular surgeons, chiefly due to their fast and irreversible polymerization. Over the past five years, however, cyanoacrylates have earned an established place in endovascular interventional radiology. Given the irreversible effects of cyanoacrylates, studies in animal models are ethically acceptable only if supported by reliable preliminary data. Many animal studies of cyanoacrylates involved the experimental creation of aneurysms or arteriovenous fistulas, whose treatment by endovascular embolization was then assessed. In clinical practice, however, injection into non-modified arteries may be desirable, for instance, to deprive a tumor of its vascular supply. To help investigators in this field select the animal models and procedures that are most appropriate for their objectives, we have reviewed all published in vivo animal studies that involved the injection of cyanoacrylates into non-modified arteries to discuss their main characteristics and endpoints.

X-ray Microtomography to Assess Determinants of In Vivo N-Butyl Cyanoacrylate Glubran®2 Polymerization: A Rabbit-Model Study

“…The mean injected volume (including into the dead space) was 0.81 mL (0.50 mL–1.95 mL) in our rabbit model, compared to 0.43 mL (0.3–0.6 mL) in a dog model. We chose rabbits because they share with rodents the advantages of small size, ease of handling and housing, and relatively low cost compared to swine [ 15 , 29 , 30 ]. The species taking account corresponding coagulation parameters and vessel size may not substantially affect the behavior of NBCA mixtures, since polymerization is initiated and propagated by anions present in all mammals [ 18 , 31 , 32 ].…”

“…To date, in clinical practice, the glue concentration in the embolizing mixture and the injection rate are adjusted empirically to ensure that polymerization occurs at the target site. This adjustment requires extensive operator training and navigation of a potentially long and tricky learning curve [ 4 , 13 , 14 , 15 , 16 ]. Existing methods used to control NBCA polymerization include the pressure-cooker or blocked-blood-flow (BBF) technique, in which a second microcatheter occludes the vessel proximally to prevent the reflux and fragmentation of the glue injected distally through the first microcatheter [ 17 ].…”

“…Existing methods used to control NBCA polymerization include the pressure-cooker or blocked-blood-flow (BBF) technique, in which a second microcatheter occludes the vessel proximally to prevent the reflux and fragmentation of the glue injected distally through the first microcatheter [ 17 ]. Moreover, the polymerization rate can be slowed by decreasing the NBCA concentration in the embolic mixture via the addition of lipiodol (Lipiodol Ultra Fluid ® [LUF], Guerbet, Villepinte, France) [ 15 , 18 , 19 ]. The slower rate gives the operator more leeway, and the radiopacity of lipiodol enables fluoroscopic monitoring [ 19 ].…”

“…It was the first cyanoacrylate glue to receive the European Union certification mark for endovascular use. Nonetheless, few studies have focused on the specific polymerization characteristics of Glubran ® 2 to better anticipate its in vivo behavior [ 15 , 22 ]. We therefore chose to use Glubran ® 2 for an in vivo animal study with the objective of assessing glue distribution in the downstream vascular network and parenchymal penetration using ex vivo X-ray microtomography (micro-CT).…”

Polymerisation of cyanoacrylates: The effect of sclero-embolic and contrast agents

“…These data are consistent with findings previously reported by other authors. 13

Figure 6.Polymerisation times for n-BCA and various pH solution mixtures. There was a slight delay in the polymerisation of n-BCA and pH-3-mixtures and a slight acceleration in the pH-11-mixtures in all n-BCA ( n = 3).

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