In vitro and in vivo studies for modified ethyl cyanoacrylate regimens for sclerotherapy

Cyanoacrylates have known for their ability to polymerize rapidly in the presence of traces of weakly basic moieties such as water. The tissue adhesive, Histoacryl(R) (N-butyl 2-cyanoacrylate), has been reported to control bleeding through endoscopic sclerotherapy. But the commercially available Histoacryl(R) is expensive, and it has the problem like other cyanoacrylates that the glue tends to flow/run away from the point of application, which is inherent to the low viscosity, making precise application difficult. In this study, ethyl cyanoacrylate (ECA), the main constituent of "super glue," was employed instead of Histoacryl(R) due to its lower cost. The aim of the research is to modify the compositions of ECA regimen and evaluate its feasibility for sclerosant application through both in vitro flow circuit model and in vivo animal tests. It was noted that the difference in the relative hardening rate between the in vitro Hepes-Tyrodes buffer flowing model and the in vivo rat model for the ECA and Histoacryl(R) was related to the existence of the blood protein, such as albumin, in the physiological milieu. It was also noticed that the ECA setting rate was greatly increased either in Hepes-Tyrodes buffer or in blood (to a comparable rate as Histoacryl(R) in vivo) by adding a few doses of caffeine, which acts as a polymerization initiator. This would lead to far better injection precision during sclerotherapy. Furthermore, in vivo histological examination for the occluded lumen of the rat's inferior vena cava and a clinical piglet portal vein occlusion experiment have suggested this new sclerosant regimen, caffeine/ECA, is of great promise in endoscopic sclerotherapy.